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Sample records for directed evolution strategy

  1. Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

    Science.gov (United States)

    Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

    2015-01-01

    Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

  2. Maternal Lipid Provisioning Mirrors Evolution of Reproductive Strategies in Direct-Developing Whelks.

    Science.gov (United States)

    Carrasco, Sergio A; Phillips, Nicole E; Sewell, Mary A

    2016-06-01

    The energetic input that offspring receive from their mothers is a well-studied maternal effect that can influence the evolution of life histories. Using the offspring of three sympatric whelks: Cominella virgata (one embryo per capsule); Cominella maculosa (multiple embryos per capsule); and Haustrum scobina (multiple embryos per capsule and nurse-embryo consumption), we examined how contrasting reproductive strategies mediate inter- and intraspecific differences in hatchling provisioning. Total lipid content (as measured in μg hatchling(-1) ± SE) was unrelated to size among the 3 species; the hatchlings of H. scobina were the smallest but had the highest lipid content (33.8 ± 8.1 μg hatchling(-1)). In offspring of C. maculosa, lipid content was 6.6 ± 0.4 μg hatchling(-1), and in offspring of C. virgata, it was 21.7 ± 3.2 μg hatchling(-1) The multi-encapsulated hatchlings of C. maculosa and H. scobina were the only species that contained the energetic lipids, wax ester (WE) and methyl ester (ME). However, the overall composition of energetic lipid between hatchlings of the two Cominella species reflected strong affinities of taxonomy, suggesting a phylogenetic evolution of the non-adelphophagic development strategy. Inter- and intracapsular variability in sibling provisioning was highest in H. scobina, a finding that implies less control of allocation to individual hatchlings in this adelphophagic developer. We suggest that interspecific variability of lipids offers a useful approach to understanding the evolution of maternal provisioning in direct-developing species. © 2016 Marine Biological Laboratory.

  3. Directed evolution strategies for enantiocomplementary haloalkane dehalogenases: from chemical waste to enantiopure building blocks.

    Science.gov (United States)

    van Leeuwen, Jan G E; Wijma, Hein J; Floor, Robert J; van der Laan, Jan-Metske; Janssen, Dick B

    2012-01-02

    We used directed evolution to obtain enantiocomplementary haloalkane dehalogenase variants that convert the toxic waste compound 1,2,3-trichloropropane (TCP) into highly enantioenriched (R)- or (S)-2,3-dichloropropan-1-ol, which can easily be converted into optically active epichlorohydrins-attractive intermediates for the synthesis of enantiopure fine chemicals. A dehalogenase with improved catalytic activity but very low enantioselectivity was used as the starting point. A strategy that made optimal use of the limited capacity of the screening assay, which was based on chiral gas chromatography, was developed. We used pair-wise site-saturation mutagenesis (SSM) of all 16 noncatalytic active-site residues during the initial two rounds of evolution. The resulting best R- and S-enantioselective variants were further improved in two rounds of site-restricted mutagenesis (SRM), with incorporation of carefully selected sets of amino acids at a larger number of positions, including sites that are more distant from the active site. Finally, the most promising mutations and positions were promoted to a combinatorial library by using a multi-site mutagenesis protocol with restricted codon sets. To guide the design of partly undefined (ambiguous) codon sets for these restricted libraries we employed structural information, the results of multiple sequence alignments, and knowledge from earlier rounds. After five rounds of evolution with screening of only 5500 clones, we obtained two strongly diverged haloalkane dehalogenase variants that give access to (R)-epichlorohydrin with 90 % ee and to (S)-epichlorohydrin with 97 % ee, containing 13 and 17 mutations, respectively, around their active sites. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Directed Evolution Strategies for Enantiocomplementary Haloalkane Dehalogenases : From Chemical Waste to Enantiopure Building Blocks

    NARCIS (Netherlands)

    van Leeuwen, Jan G. E.; Wijma, Hein J.; Floor, Robert J.; van der Laan, Jan-Metske; Janssen, Dick B.

    2012-01-01

    We used directed evolution to obtain enantiocomplementary haloalkane dehalogenase variants that convert the toxic waste compound 1,2,3-trichloropropane (TCP) into highly enantioenriched (R)- or (S)-2,3-dichloropropan-1-ol, which can easily be converted into optically active

  5. Contemporary evolution strategies

    CERN Document Server

    Bäck, Thomas; Krause, Peter

    2013-01-01

    Evolution strategies have more than 50 years of history in the field of evolutionary computation. Since the early 1990s, many algorithmic variations of evolution strategies have been developed, characterized by the fact that they use the so-called derandomization concept for strategy parameter adaptation. Most importantly, the covariance matrix adaptation strategy (CMA-ES) and its successors are the key representatives of this group of contemporary evolution strategies. This book provides an overview of the key algorithm developments between 1990 and 2012, including brief descriptions of the a

  6. Engineering better biomass-degrading ability into a GH11 xylanase using a directed evolution strategy

    Directory of Open Access Journals (Sweden)

    Song Letian

    2012-01-01

    Full Text Available Abstract Background Improving the hydrolytic performance of hemicellulases on lignocellulosic biomass is of considerable importance for second-generation biorefining. To address this problem, and also to gain greater understanding of structure-function relationships, especially related to xylanase action on complex biomass, we have implemented a combinatorial strategy to engineer the GH11 xylanase from Thermobacillus xylanilyticus (Tx-Xyn. Results Following in vitro enzyme evolution and screening on wheat straw, nine best-performing clones were identified, which display mutations at positions 3, 6, 27 and 111. All of these mutants showed increased hydrolytic activity on wheat straw, and solubilized arabinoxylans that were not modified by the parental enzyme. The most active mutants, S27T and Y111T, increased the solubilization of arabinoxylans from depleted wheat straw 2.3-fold and 2.1-fold, respectively, in comparison to the wild-type enzyme. In addition, five mutants, S27T, Y111H, Y111S, Y111T and S27T-Y111H increased total hemicellulose conversion of intact wheat straw from 16.7%tot. xyl (wild-type Tx-Xyn to 18.6% to 20.4%tot. xyl. Also, all five mutant enzymes exhibited a better ability to act in synergy with a cellulase cocktail (Accellerase 1500, thus procuring increases in overall wheat straw hydrolysis. Conclusions Analysis of the results allows us to hypothesize that the increased hydrolytic ability of the mutants is linked to (i improved ligand binding in a putative secondary binding site, (ii the diminution of surface hydrophobicity, and/or (iii the modification of thumb flexibility, induced by mutations at position 111. Nevertheless, the relatively modest improvements that were observed also underline the fact that enzyme engineering alone cannot overcome the limits imposed by the complex organization of the plant cell wall and the lignin barrier.

  7. DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

    Science.gov (United States)

    Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

    2014-12-20

    Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

  8. Novel Random Mutagenesis Method for Directed Evolution.

    Science.gov (United States)

    Feng, Hong; Wang, Hai-Yan; Zhao, Hong-Yan

    2017-01-01

    Directed evolution is a powerful strategy for gene mutagenesis, and has been used for protein engineering both in scientific research and in the biotechnology industry. The routine method for directed evolution was developed by Stemmer in 1994 (Stemmer, Proc Natl Acad Sci USA 91, 10747-10751, 1994; Stemmer, Nature 370, 389-391, 1994). Since then, various methods have been introduced, each of which has advantages and limitations depending upon the targeted genes and procedure. In this chapter, a novel alternative directed evolution method which combines mutagenesis PCR with dITP and fragmentation by endonuclease V is described. The kanamycin resistance gene is used as a reporter gene to verify the novel method for directed evolution. This method for directed evolution has been demonstrated to be efficient, reproducible, and easy to manipulate in practice.

  9. Machine learning for evolution strategies

    CERN Document Server

    Kramer, Oliver

    2016-01-01

    This book introduces numerous algorithmic hybridizations between both worlds that show how machine learning can improve and support evolution strategies. The set of methods comprises covariance matrix estimation, meta-modeling of fitness and constraint functions, dimensionality reduction for search and visualization of high-dimensional optimization processes, and clustering-based niching. After giving an introduction to evolution strategies and machine learning, the book builds the bridge between both worlds with an algorithmic and experimental perspective. Experiments mostly employ a (1+1)-ES and are implemented in Python using the machine learning library scikit-learn. The examples are conducted on typical benchmark problems illustrating algorithmic concepts and their experimental behavior. The book closes with a discussion of related lines of research.

  10. Effective Strategies for Teaching Evolution: The Primary Evolution Project

    Science.gov (United States)

    Hatcher, Chris

    2015-01-01

    When Chris Hatcher joined the Primary Evolution Project team at the University of Reading, his goal was to find effective strategies to teach evolution in a way that keeps children engaged and enthused. Hatcher has collaborated with colleagues at the University's Institute of Education to break the evolution unit down into distinct topics and…

  11. City Planning Evolution - Urban Development Directions in the Transition Period

    Directory of Open Access Journals (Sweden)

    Mircea Grigorovschi

    2010-03-01

    Full Text Available Urban evolution post 1989 has a series of specific characteristics mainly on a spatial-territorial plane. Determination of the main developing factors and urban evolution directions (dimensions, rhythm, expansion level, centrifugal and axial character, concentric, centripetal, functional evolution, tendencies and social implications, etc. represents a necessity and obligation for action from professionals in urban and landscaping fields. This necessity even arises from the perspective of the need for realizing strategies, planning, documentation and urban studies, which must intervene correctively in the evolution of areas with structural problems and to guide urban evolution towards the main goal namely the growth in residential quality of life in human settlements.

  12. Inertia in strategy switching transforms the strategy evolution.

    Science.gov (United States)

    Zhang, Yanling; Fu, Feng; Wu, Te; Xie, Guangming; Wang, Long

    2011-12-01

    A recent experimental study [Traulsen et al., Proc. Natl. Acad. Sci. 107, 2962 (2010)] shows that human strategy updating involves both direct payoff comparison and the cost of switching strategy, which is equivalent to inertia. However, it remains largely unclear how such a predisposed inertia affects 2 × 2 games in a well-mixed population of finite size. To address this issue, the "inertia bonus" (strategy switching cost) is added to the learner payoff in the Fermi process. We find how inertia quantitatively shapes the stationary distribution and that stochastic stability under inertia exhibits three regimes, with each covering seven regions in the plane spanned by two inertia parameters. We also obtain the extended "1/3" rule with inertia and the speed criterion with inertia; these two findings hold for a population above two. We illustrate the above results in the framework of the Prisoner's Dilemma game. As inertia varies, two intriguing stationary distributions emerge: the probability of coexistence state is maximized, or those of two full states are simultaneously peaked. Our results may provide useful insights into how the inertia of changing status quo acts on the strategy evolution and, in particular, the evolution of cooperation.

  13. Micro-droplet based directed evolution outperforms conventional laboratory evolution

    DEFF Research Database (Denmark)

    Sjostrom, Staffan L.; Huang, Mingtao; Nielsen, Jens

    2014-01-01

    We present droplet adaptive laboratory evolution (DrALE), a directed evolution method used to improve industrial enzyme producing microorganisms for e.g. feedstock digestion. DrALE is based linking a desired phenotype to growth rate allowing only desired cells to proliferate. Single cells are con...... a whole-genome mutated library of yeast cells for α-amylase activity....

  14. Strategy intervention for the evolution of fairness.

    Directory of Open Access Journals (Sweden)

    Yanling Zhang

    Full Text Available The 'irrational' preference for fairness has attracted increasing attention. Although previous studies have focused on the effects of spitefulness on the evolution of fairness, they did not consider non-monotonic rejections shown in behavioral experiments. In this paper, we introduce a non-monotonic rejection in an evolutionary model of the Ultimatum Game. We propose strategy intervention to study the evolution of fairness in general structured populations. By sequentially adding five strategies into the competition between a fair strategy and a selfish strategy, we arrive at the following conclusions. First, the evolution of fairness is inhibited by altruism, but it is promoted by spitefulness. Second, the non-monotonic rejection helps fairness overcome selfishness. Particularly for group-structured populations, we analytically investigate how fairness, selfishness, altruism, and spitefulness are affected by population size, mutation, and migration in the competition among seven strategies. Our results may provide important insights into understanding the evolutionary origin of fairness.

  15. Directed evolution of enzymes using microfluidic chips

    Science.gov (United States)

    Pilát, Zdeněk.; Ježek, Jan; Šmatlo, Filip; Kaůka, Jan; Zemánek, Pavel

    2016-12-01

    Enzymes are highly versatile and ubiquitous biological catalysts. They can greatly accelerate large variety of reactions, while ensuring appropriate catalytic activity and high selectivity. These properties make enzymes attractive biocatalysts for a wide range of industrial and biomedical applications. Over the last two decades, directed evolution of enzymes has transformed the field of protein engineering. We have devised microfluidic systems for directed evolution of haloalkane dehalogenases in emulsion droplets. In such a device, individual bacterial cells producing mutated variants of the same enzyme are encapsulated in microdroplets and supplied with a substrate. The conversion of a substrate by the enzyme produced by a single bacterium changes the pH in the droplet which is signalized by pH dependent fluorescence probe. The droplets with the highest enzymatic activity can be separated directly on the chip by dielectrophoresis and the resultant cell lineage can be used for enzyme production or for further rounds of directed evolution. This platform is applicable for fast screening of large libraries in directed evolution experiments requiring mutagenesis at multiple sites of a protein structure.

  16. Evolution of genetic architecture under directional selection.

    Science.gov (United States)

    Hansen, Thomas F; Alvarez-Castro, José M; Carter, Ashley J R; Hermisson, Joachim; Wagner, Günter P

    2006-08-01

    We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis.

  17. Mixed integer evolution strategies for parameter optimization.

    Science.gov (United States)

    Li, Rui; Emmerich, Michael T M; Eggermont, Jeroen; Bäck, Thomas; Schütz, M; Dijkstra, J; Reiber, J H C

    2013-01-01

    Evolution strategies (ESs) are powerful probabilistic search and optimization algorithms gleaned from biological evolution theory. They have been successfully applied to a wide range of real world applications. The modern ESs are mainly designed for solving continuous parameter optimization problems. Their ability to adapt the parameters of the multivariate normal distribution used for mutation during the optimization run makes them well suited for this domain. In this article we describe and study mixed integer evolution strategies (MIES), which are natural extensions of ES for mixed integer optimization problems. MIES can deal with parameter vectors consisting not only of continuous variables but also with nominal discrete and integer variables. Following the design principles of the canonical evolution strategies, they use specialized mutation operators tailored for the aforementioned mixed parameter classes. For each type of variable, the choice of mutation operators is governed by a natural metric for this variable type, maximal entropy, and symmetry considerations. All distributions used for mutation can be controlled in their shape by means of scaling parameters, allowing self-adaptation to be implemented. After introducing and motivating the conceptual design of the MIES, we study the optimality of the self-adaptation of step sizes and mutation rates on a generalized (weighted) sphere model. Moreover, we prove global convergence of the MIES on a very general class of problems. The remainder of the article is devoted to performance studies on artificial landscapes (barrier functions and mixed integer NK landscapes), and a case study in the optimization of medical image analysis systems. In addition, we show that with proper constraint handling techniques, MIES can also be applied to classical mixed integer nonlinear programming problems.

  18. Blackboxing: social learning strategies and cultural evolution.

    Science.gov (United States)

    Heyes, Cecilia

    2016-05-05

    Social learning strategies (SLSs) enable humans, non-human animals, and artificial agents to make adaptive decisions aboutwhenthey should copy other agents, andwhothey should copy. Behavioural ecologists and economists have discovered an impressive range of SLSs, and explored their likely impact on behavioural efficiency and reproductive fitness while using the 'phenotypic gambit'; ignoring, or remaining deliberately agnostic about, the nature and origins of the cognitive processes that implement SLSs. Here I argue that this 'blackboxing' of SLSs is no longer a viable scientific strategy. It has contributed, through the 'social learning strategies tournament', to the premature conclusion that social learning is generally better than asocial learning, and to a deep puzzle about the relationship between SLSs and cultural evolution. The puzzle can be solved by recognizing that whereas most SLSs are 'planetary'--they depend on domain-general cognitive processes--some SLSs, found only in humans, are 'cook-like'--they depend on explicit, metacognitive rules, such ascopy digital natives. These metacognitive SLSs contribute to cultural evolution by fostering the development of processes that enhance the exclusivity, specificity, and accuracy of social learning. © 2016 The Author(s).

  19. Blackboxing: social learning strategies and cultural evolution

    Science.gov (United States)

    Heyes, Cecilia

    2016-01-01

    Social learning strategies (SLSs) enable humans, non-human animals, and artificial agents to make adaptive decisions about when they should copy other agents, and who they should copy. Behavioural ecologists and economists have discovered an impressive range of SLSs, and explored their likely impact on behavioural efficiency and reproductive fitness while using the ‘phenotypic gambit’; ignoring, or remaining deliberately agnostic about, the nature and origins of the cognitive processes that implement SLSs. Here I argue that this ‘blackboxing' of SLSs is no longer a viable scientific strategy. It has contributed, through the ‘social learning strategies tournament', to the premature conclusion that social learning is generally better than asocial learning, and to a deep puzzle about the relationship between SLSs and cultural evolution. The puzzle can be solved by recognizing that whereas most SLSs are ‘planetary'—they depend on domain-general cognitive processes—some SLSs, found only in humans, are ‘cook-like'—they depend on explicit, metacognitive rules, such as copy digital natives. These metacognitive SLSs contribute to cultural evolution by fostering the development of processes that enhance the exclusivity, specificity, and accuracy of social learning. PMID:27069046

  20. Evolution Strategies in the Multipoint Connections Routing

    Directory of Open Access Journals (Sweden)

    L. Krulikovska

    2010-09-01

    Full Text Available Routing of multipoint connections plays an important role in final cost and quality of a found connection. New algorithms with better results are still searched. In this paper, a possibility of using the evolution strategies (ES for routing is presented. Quality of found connection is evaluated from the view of final cost and time spent on a searching procedure. First, parametrical analysis of results of the ES are discussed and compared with the Prim’s algorithm, which was chosen as a representative of the deterministic routing algorithms. Second, ways for improving the ES are suggested and implemented. The obtained results are reviewed. The main improvements are specified and discussed in conclusion.

  1. Efficient receiver tuning using differential evolution strategies

    Science.gov (United States)

    Wheeler, Caleb H.; Toland, Trevor G.

    2016-08-01

    Differential evolution (DE) is a powerful and computationally inexpensive optimization strategy that can be used to search an entire parameter space or to converge quickly on a solution. The Kilopixel Array Pathfinder Project (KAPPa) is a heterodyne receiver system delivering 5 GHz of instantaneous bandwidth in the tuning range of 645-695 GHz. The fully automated KAPPa receiver test system finds optimal receiver tuning using performance feedback and DE. We present an adaptation of DE for use in rapid receiver characterization. The KAPPa DE algorithm is written in Python 2.7 and is fully integrated with the KAPPa instrument control, data processing, and visualization code. KAPPa develops the technologies needed to realize heterodyne focal plane arrays containing 1000 pixels. Finding optimal receiver tuning by investigating large parameter spaces is one of many challenges facing the characterization phase of KAPPa. This is a difficult task via by-hand techniques. Characterizing or tuning in an automated fashion without need for human intervention is desirable for future large scale arrays. While many optimization strategies exist, DE is ideal for time and performance constraints because it can be set to converge to a solution rapidly with minimal computational overhead. We discuss how DE is utilized in the KAPPa system and discuss its performance and look toward the future of 1000 pixel array receivers and consider how the KAPPa DE system might be applied.

  2. Evolution of strategies for modern rechargeable batteries.

    Science.gov (United States)

    Goodenough, John B

    2013-05-21

    This Account provides perspective on the evolution of the rechargeable battery and summarizes innovations in the development of these devices. Initially, I describe the components of a conventional rechargeable battery along with the engineering parameters that define the figures of merit for a single cell. In 1967, researchers discovered fast Na(+) conduction at 300 K in Na β,β''-alumina. Since then battery technology has evolved from a strongly acidic or alkaline aqueous electrolyte with protons as the working ion to an organic liquid-carbonate electrolyte with Li(+) as the working ion in a Li-ion battery. The invention of the sodium-sulfur and Zebra batteries stimulated consideration of framework structures as crystalline hosts for mobile guest alkali ions, and the jump in oil prices in the early 1970s prompted researchers to consider alternative room-temperature batteries with aprotic liquid electrolytes. With the existence of Li primary cells and ongoing research on the chemistry of reversible Li intercalation into layered chalcogenides, industry invested in the production of a Li/TiS2 rechargeable cell. However, on repeated recharge, dendrites grew across the electrolyte from the anode to the cathode, leading to dangerous short-circuits in the cell in the presence of the flammable organic liquid electrolyte. Because lowering the voltage of the anode would prevent cells with layered-chalcogenide cathodes from competing with cells that had an aqueous electrolyte, researchers quickly abandoned this effort. However, once it was realized that an oxide cathode could offer a larger voltage versus lithium, researchers considered the extraction of Li from the layered LiMO2 oxides with M = Co or Ni. These oxide cathodes were fabricated in a discharged state, and battery manufacturers could not conceive of assembling a cell with a discharged cathode. Meanwhile, exploration of Li intercalation into graphite showed that reversible Li insertion into carbon occurred

  3. Using 2-Opt based evolution strategy for travelling salesman problem

    Directory of Open Access Journals (Sweden)

    Kenan Karagul

    2016-03-01

    Full Text Available Harmony search algorithm that matches the (µ+1 evolution strategy, is a heuristic method simulated by the process of music improvisation. In this paper, a harmony search algorithm is directly used for the travelling salesman problem. Instead of conventional selection operators such as roulette wheel, the transformation of real number values of harmony search algorithm to order index of vertex representation and improvement of solutions are obtained by using the 2-Opt local search algorithm. Then, the obtained algorithm is tested on two different parameter groups of TSPLIB. The proposed method is compared with classical 2-Opt which randomly started at each step and best known solutions of test instances from TSPLIB. It is seen that the proposed algorithm offers valuable solutions.

  4. Iran's Sea Power Strategy: Goals and Evolution

    National Research Council Canada - National Science Library

    Walker, John

    1997-01-01

    This thesis examines the intent of Iran's sea power strategy using a multipart analysis including a historical review of the transition of Iran's naval power through the Iranian Revolution, Iran-Iraq...

  5. modelling of directed evolution: Implications for experimental design and stepwise evolution

    OpenAIRE

    Wedge , David C.; Rowe , William; Kell , Douglas B.; Knowles , Joshua

    2009-01-01

    In silico modelling of directed evolution: Implications for experimental design and stepwise evolution correspondence: Corresponding author. Tel.: +441613065145. (Wedge, David C.) (Wedge, David C.) Manchester Interdisciplinary Biocentre, University of Manchester - 131 Princess Street--> , Manchester--> , M1 7ND--> - UNITED KINGDOM (Wedge, David C.) UNITED KINGDOM (Wedge, David C.) Man...

  6. The Evolution of Exploitation Strategies by Myrmecophiles

    DEFF Research Database (Denmark)

    Schär, Sämi

    than outside ant nests (M. rubra) as well. This fungus can kill ant associated lycaenid larvae, justifying the assumption that these benefit from the entomopathogen poor environment of ant nests. This could explain why natural selection may act in favour of this strategy. In the third chapter I......Myrmecophiles are animals which have evolved to live in the nests of ants. This life history strategy appears in animals as different as insects, spiders, snails, crustaceans and even snakes. Myrmecophiles are very speciose with estimates of up to 100'000 species, which raises the question why...... this strategy has evolved so frequently and is maintained by natural selection. The type of association between Myrmecophiles and ants ranges from mutualistic through to parasitic. These types of symbioses can also be found between and within species of ants. Ant associations can therefore be broadly...

  7. NEW CO-EVOLUTION STRATEGIES OF THIRD MILLENNIUM; METHODOLOGICAL ASPECT

    Directory of Open Access Journals (Sweden)

    E. K. Bulygo

    2006-01-01

    Full Text Available The paper is devoted to an application of the co-evolution methodology to the social space. Principles of instability and non-linearity that are typical for contemporary natural science are used as a theoretical background of a new social methodology. Authors try to prove that the co-evolution strategy has a long pre-history in the ancient oriental philosophy and manifests itself in forms of modem culture

  8. Collection Directions: The Evolution of Library Collections and Collecting

    Science.gov (United States)

    Dempsey, Lorcan; Malpas, Constance; Lavoie, Brian

    2014-01-01

    This article takes a broad view of the evolution of collecting behaviors in a network environment and suggests some future directions based on various simple models. The authors look at the changing dynamics of print collections, at the greater engagement with research and learning behaviors, and at trends in scholarly communication. The goal is…

  9. Directed evolution: selecting today's biocatalysts : selecting today's biocatalysts

    NARCIS (Netherlands)

    Otten, Linda; Quax, Wim

    2005-01-01

    Directed evolution has become a full-grown tool in molecular biology nowadays. The methods that are involved in creating a mutant library are extensive and can be divided into several categories according to their basic ideas. Furthermore, both screening and selection can be used to target the

  10. The Evolution of the Direct Marketing Industry in Italy

    OpenAIRE

    M.C. OSTILLIO; G. TROILO

    1996-01-01

    The paper reports the evolution of the direct marketing (DM) industry and activties in Italy, by comparing Italian data with data from other large international markets. The comparison regards motivations behind investments in DM, the type of investment, the services offered by DM agencies.

  11. Directed Evolution of Membrane Transport Using Synthetic Selections

    DEFF Research Database (Denmark)

    Bali, Anne Pihl; Genee, Hans J.; Sommer, Morten O. A.

    2018-01-01

    systems that enable selective growth of E. coli cells only if they functionally express an importer that is specific to the biosensor ligand. Using this system in a directed evolution framework, we successfully engineer the specificity of nicotinamide riboside transporters, PnuC, to accept thiamine...

  12. Entrepreneurship ecosystem evolution strategy of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Muhammad Rahatullah Khan

    2016-10-01

    Full Text Available In majority of times when a potential start-up strikes a brilliant business idea, he/she has little knowledge of ‘how to move from there’. They lack information on the stakeholders of entrepreneurship ecosystem who can help and assist these startups in numerous ways and help them materialize their concepts. Availability of this information will help the ecosystem stakeholders to avoid replication and duplication of efforts. Similarly, knowledge of status quo helps identify opportunities and supports plan development to endeavor through right strategy for the start-up. Critical review of existing initiatives of Saudi Arabia for entrepreneurship growth and identification of the existing stakeholders of the entrepreneurship in the country is conducted. Similarly their work and potential for practicable interventions to further entrepreneurship reflecting country’s economic development process is examined. This paper benefits from a cross sectional basic study of Saudi Arabia that utilized primary and secondary sources to discover the initiatives, understand entrepreneurship growth and then map the national entrepreneurship ecosystem. A number of interviews from CEO’s, General Managers and other senior executives were carried out to know the role of the different organizations in entrepreneurship growth. It was coupled with a detailed secondary research from existing resources. It has been identified that the ecosystem is swiftly expanding but yet under development and infancy stage where the institutions are prospering. The research is based on country analysis. The paper also shows that the Saudi Arabian government has taken proactive stance in developing the entrepreneurship ecosystem and startup landscape and highlights the transformation of the ecosystem strategy.

  13. Research on Taxi Driver Strategy Game Evolution with Carpooling Detour

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-01-01

    Full Text Available For the problem of taxi carpooling detour, this paper studies driver strategy choice with carpooling detour. The model of taxi driver strategy evolution with carpooling detour is built based on prospect theory and evolution game theory. Driver stable strategies are analyzed under the conditions of complaint mechanism and absence of mechanism, respectively. The results show that passenger’s complaint mechanism can effectively decrease the phenomenon of driver refusing passengers with carpooling detour. When probability of passenger complaint reaches a certain level, the stable strategy of driver is to take carpooling detour passengers. Meanwhile, limiting detour distance and easing traffic congestion can decrease the possibility of refusing passengers. These conclusions have a certain guiding significance to formulating taxi policy.

  14. ESA Earth Observation Ground Segment Evolution Strategy

    Science.gov (United States)

    Benveniste, J.; Albani, M.; Laur, H.

    2016-12-01

    One of the key elements driving the evolution of EO Ground Segments, in particular in Europe, has been to enable the creation of added value from EO data and products. This requires the ability to constantly adapt and improve the service to a user base expanding far beyond the `traditional' EO user community of remote sensing specialists. Citizen scientists, the general public, media and educational actors form another user group that is expected to grow. Technological advances, Open Data policies, including those implemented by ESA and the EU, as well as an increasing number of satellites in operations (e.g. Copernicus Sentinels) have led to an enormous increase in available data volumes. At the same time, even with modern network and data handling services, fewer users can afford to bulk-download and consider all potentially relevant data and associated knowledge. The "EO Innovation Europe" concept is being implemented in Europe in coordination between the European Commission, ESA and other European Space Agencies, and industry. This concept is encapsulated in the main ideas of "Bringing the User to the Data" and "Connecting the Users" to complement the traditional one-to-one "data delivery" approach of the past. Both ideas are aiming to better "empower the users" and to create a "sustainable system of interconnected EO Exploitation Platforms", with the objective to enable large scale exploitation of European EO data assets for stimulating innovation and to maximize their impact. These interoperable/interconnected platforms are virtual environments in which the users - individually or collaboratively - have access to the required data sources and processing tools, as opposed to downloading and handling the data `at home'. EO-Innovation Europe has been structured around three elements: an enabling element (acting as a back office), a stimulating element and an outreach element (acting as a front office). Within the enabling element, a "mutualisation" of efforts

  15. A Nonstationary Markov Model Detects Directional Evolution in Hymenopteran Morphology.

    Science.gov (United States)

    Klopfstein, Seraina; Vilhelmsen, Lars; Ronquist, Fredrik

    2015-11-01

    Directional evolution has played an important role in shaping the morphological, ecological, and molecular diversity of life. However, standard substitution models assume stationarity of the evolutionary process over the time scale examined, thus impeding the study of directionality. Here we explore a simple, nonstationary model of evolution for discrete data, which assumes that the state frequencies at the root differ from the equilibrium frequencies of the homogeneous evolutionary process along the rest of the tree (i.e., the process is nonstationary, nonreversible, but homogeneous). Within this framework, we develop a Bayesian approach for testing directional versus stationary evolution using a reversible-jump algorithm. Simulations show that when only data from extant taxa are available, the success in inferring directionality is strongly dependent on the evolutionary rate, the shape of the tree, the relative branch lengths, and the number of taxa. Given suitable evolutionary rates (0.1-0.5 expected substitutions between root and tips), accounting for directionality improves tree inference and often allows correct rooting of the tree without the use of an outgroup. As an empirical test, we apply our method to study directional evolution in hymenopteran morphology. We focus on three character systems: wing veins, muscles, and sclerites. We find strong support for a trend toward loss of wing veins and muscles, while stationarity cannot be ruled out for sclerites. Adding fossil and time information in a total-evidence dating approach, we show that accounting for directionality results in more precise estimates not only of the ancestral state at the root of the tree, but also of the divergence times. Our model relaxes the assumption of stationarity and reversibility by adding a minimum of additional parameters, and is thus well suited to studying the nature of the evolutionary process in data sets of limited size, such as morphology and ecology. © The Author

  16. Evolution of egoism on semi-directed and undirected Barabási-Albert networks

    Science.gov (United States)

    Lima, F. W. S.

    2015-05-01

    Through Monte Carlo simulations, we study the evolution of the four strategies: Ethnocentric, altruistic, egoistic and cosmopolitan in one community of individuals. Interactions and reproduction among computational agents are simulated on undirected and semi-directed Barabási-Albert (BA) networks. We study the Hammond-Axelrod (HA) model on undirected and semi-directed BA networks for the asexual reproduction case. With a small modification in the traditional HA model, our simulations showed that egoism wins, differently from other results found in the literature where ethnocentric strategy is common. Here, mechanisms such as reciprocity are absent.

  17. Memory-n strategies of direct reciprocity.

    Science.gov (United States)

    Hilbe, Christian; Martinez-Vaquero, Luis A; Chatterjee, Krishnendu; Nowak, Martin A

    2017-05-02

    Humans routinely use conditionally cooperative strategies when interacting in repeated social dilemmas. They are more likely to cooperate if others cooperated before, and are ready to retaliate if others defected. To capture the emergence of reciprocity, most previous models consider subjects who can only choose from a restricted set of representative strategies, or who react to the outcome of the very last round only. As players memorize more rounds, the dimension of the strategy space increases exponentially. This increasing computational complexity renders simulations for individuals with higher cognitive abilities infeasible, especially if multiplayer interactions are taken into account. Here, we take an axiomatic approach instead. We propose several properties that a robust cooperative strategy for a repeated multiplayer dilemma should have. These properties naturally lead to a unique class of cooperative strategies, which contains the classical Win-Stay Lose-Shift rule as a special case. A comprehensive numerical analysis for the prisoner's dilemma and for the public goods game suggests that strategies of this class readily evolve across various memory- n spaces. Our results reveal that successful strategies depend not only on how cooperative others were in the past but also on the respective context of cooperation.

  18. Automatic Clustering Using FSDE-Forced Strategy Differential Evolution

    Science.gov (United States)

    Yasid, A.

    2018-01-01

    Clustering analysis is important in datamining for unsupervised data, cause no adequate prior knowledge. One of the important tasks is defining the number of clusters without user involvement that is known as automatic clustering. This study intends on acquiring cluster number automatically utilizing forced strategy differential evolution (AC-FSDE). Two mutation parameters, namely: constant parameter and variable parameter are employed to boost differential evolution performance. Four well-known benchmark datasets were used to evaluate the algorithm. Moreover, the result is compared with other state of the art automatic clustering methods. The experiment results evidence that AC-FSDE is better or competitive with other existing automatic clustering algorithm.

  19. Selection platforms for directed evolution in synthetic biology.

    Science.gov (United States)

    Tizei, Pedro A G; Csibra, Eszter; Torres, Leticia; Pinheiro, Vitor B

    2016-08-15

    Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from simple systems made from biological molecules-gaining a deeper understanding of life in the process. Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of engineering even the most highly conserved biological processes. It encompasses a range of methodologies to create variation in a population and to select individual variants with the desired function-be it a ligand, enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin all evolution platforms and review some of the recent contributions from directed evolution to synthetic biology, in particular methods that have been used to engineer the Central Dogma and the genetic code. © 2016 The Author(s).

  20. Evolution of Strategies for "Prisoner's Dilemma" using Genetic Algorithm

    OpenAIRE

    Heinz, Jan

    2010-01-01

    The subject of this thesis is the software application "Prisoner's Dilemma". The program creates a population of players of "Prisoner's Dilemma", has them play against each other, and - based on their results - performs an evolution of their strategies by means of a genetic algorithm (selection, mutation, and crossover). The program was written in Microsoft Visual Studio, in the C++ programming language, and its interface makes use of the .NET Framework. The thesis includes examples of strate...

  1. An Emerging Strategy of "Direct" Research.

    Science.gov (United States)

    Mintzberg, Henry

    1979-01-01

    Discusses seven basic themes that underlie the author's "direct research" activities. These themes include reliance on research based on description and induction instead of prescription and deduction, and the measurement of many elements in real settings, supported by anecdote, instead of few variables in perceptual terms from a…

  2. Effects of Direct and Indirect Instructional Strategies on Students ...

    African Journals Online (AJOL)

    First Lady

    2012-10-27

    Oct 27, 2012 ... Counseling, University of Port Harcourt, Rivers State. Phone: +234(0) ... Mathematics using Direct Instructional strategy, while Group B students were taught using ... strategy; significant difference existed between direct and indirect instruction ..... is to ensure individual student's mastery of the subject matter.

  3. Evolution of group-wise cooperation: Is direct reciprocity insufficient?

    Science.gov (United States)

    Kurokawa, Shun; Ihara, Yasuo

    2017-02-21

    Group-wise cooperation, or cooperation among three or more individuals, is an integral part of human societies. It is likely that group-wise cooperation also played a crucial role in the survival of early hominins, who were confronted with novel environmental challenges, long before the emergence of Homo sapiens. However, previous theoretical and empirical studies, focusing mainly on modern humans, have tended to suggest that evolution of cooperation in sizable groups cannot be explained by simple direct reciprocity and requires some additional mechanisms (reputation, punishment, etc.), which are cognitively too demanding for early hominins. As a partial resolution of the paradox, our recent analysis of a stochastic evolutionary model, which considers the effect of random drift, has revealed that evolution of group-wise cooperation is more likely to occur in larger groups when an individual's share of the benefit produced by one cooperator does not decrease with increasing group size (i.e., goods are non-rivalrous). In this paper, we further extend our previous analysis to explore possible consequences of introducing rare mistakes in behavior or imperfect information about behavior of others on the model outcome. Analyses of the extended models show that evolution of group-wise cooperation can be facilitated by large group size even when individuals intending to cooperate sometimes fail to do so or when all the information about the past behavior of group members is not available. We argue, therefore, that evolution of cooperation in sizable groups does not necessarily require other mechanisms than direct reciprocity if the goods to be produced via group-wise cooperation are non-rivalrous. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Battery parameterisation based on differential evolution via a boundary evolution strategy

    DEFF Research Database (Denmark)

    Yang, Guangya

    2013-01-01

    the advances of evolutionary algorithms (EAs). Differential evolution (DE) is selected and modified to parameterise an equivalent circuit model of lithium-ion batteries. A boundary evolution strategy (BES) is developed and incorporated into the DE to update the parameter boundaries during the parameterisation......, as the equivalent circuit model is an abstract map of the battery electric characteristics, the determination of the possible ranges of parameters can be a challenging task. In this paper, an efficient yet easy to implement method is proposed to parameterise the equivalent circuit model of batteries utilising...

  5. Risk evaluation mitigation strategies: the evolution of risk management policy.

    Science.gov (United States)

    Hollingsworth, Kristen; Toscani, Michael

    2013-04-01

    The United States Food and Drug Administration (FDA) has the primary regulatory responsibility to ensure that medications are safe and effective both prior to drug approval and while the medication is being actively marketed by manufacturers. The responsibility for safe medications prior to marketing was signed into law in 1938 under the Federal Food, Drug, and Cosmetic Act; however, a significant risk management evolution has taken place since 1938. Additional federal rules, entitled the Food and Drug Administration Amendments Act, were established in 2007 and extended the government's oversight through the addition of a Risk Evaluation and Mitigation Strategy (REMS) for certain drugs. REMS is a mandated strategy to manage a known or potentially serious risk associated with a medication or biological product. Reasons for this extension of oversight were driven primarily by the FDA's movement to ensure that patients and providers are better informed of drug therapies and their specific benefits and risks prior to initiation. This article provides an historical perspective of the evolution of medication risk management policy and includes a review of REMS programs, an assessment of the positive and negative aspects of REMS, and provides suggestions for planning and measuring outcomes. In particular, this publication presents an overview of the evolution of the REMS program and its implications.

  6. TRENDS IN THE EVOLUTION OF WORLDWIDE FOREIGN DIRECT INVESTMENTS

    Directory of Open Access Journals (Sweden)

    Maria Ramona Sarbu

    2014-06-01

    Full Text Available The flows of foreign direct investments constitutes a major component of the phenomena that manifest themselves in the world economy, these representing financial resources geared toward a particular investment area that allow those who invest to develop operations over which they have the control and the decision-making power. Given the fact that the world economy is characterized by the increasing interconnectedness of national states as a result of spreading the links in the spheres of economic, political, social and cultural life, following starting with 2008 a period of unusual developments, the purpose of the paper is to analyze the evolution of worldwide foreign direct investment (FDI inflows, before and after the onset of the global economic crisis.

  7. Textural Evolution During Micro Direct Metal Deposition of NiTi Alloy

    Science.gov (United States)

    Khademzadeh, Saeed; Bariani, Paolo F.; Bruschi, Stefania

    2018-03-01

    In this research, a micro direct metal deposition process, newly developed as a potential method for micro additive manufacturing was used to fabricate NiTi builds. The effect of scanning strategy on grain growth and textural evolution was investigated using scanning electron microscope equipped with electron backscattered diffraction detector. Investigations showed that, the angle between the successive single tracks has an important role in grain size distribution and textural evolution of NiTi phase. Unidirectional laser beam scanning pattern developed a fiber texture; conversely, a backward and forward scanning pattern developed a strong ‖‖ RD texture on the surface of NiTi cubic samples produced by micro direct metal deposition.

  8. Evolution strategy based optimal chiller loading for saving energy

    International Nuclear Information System (INIS)

    Chang, Y.-C.; Lee, C.-Y.; Chen, C.-R.; Chou, C.-J.; Chen, W.-H.; Chen, W.-H.

    2009-01-01

    This study employs evolution strategy (ES) to solve optimal chiller loading (OCL) problem. ES overcomes the flaw that Lagrangian method is not adaptable for solving OCL as the power consumption models or the kW-PLR (partial load ratio) curves include convex functions and concave functions simultaneously. The complicated process of evolution by the genetic algorithm (GA) method for solving OCL can also be simplified by the ES method. This study uses the PLR of chiller as the variable to be solved for the decoupled air conditioning system. After analysis and comparison of the case study, it has been concluded that this method not only solves the problems of Lagrangian method and GA method, but also produces results with high accuracy within a rapid timeframe. It can be perfectly applied to the operation of air conditioning systems

  9. The evolution of intellectual property strategy in innovation ecosystems

    DEFF Research Database (Denmark)

    Holgersson, Marcus; Granstrand, Ove; Bogers, Marcel

    2017-01-01

    In this article, we attempt to extend and nuance the debate on intellectual property (IP) strategy, appropriation, and open innovation in dynamic and systemic innovation contexts. We present the case of four generations of mobile telecommunications systems (covering the period 1980-2015), and des......In this article, we attempt to extend and nuance the debate on intellectual property (IP) strategy, appropriation, and open innovation in dynamic and systemic innovation contexts. We present the case of four generations of mobile telecommunications systems (covering the period 1980......-2015), and describe and analyze the co-evolution of strategic IP management and innovation ecosystems. Throughout this development, technologies and technological relationships were governed with different and shifting degrees of formality. Simultaneously, firms differentiated technology accessibility across actors...

  10. Directed evolution of a thermostable l-aminoacylase biocatalyst

    DEFF Research Database (Denmark)

    Parker, Brenda M.; Taylor, Ian N.; Woodley, John

    2011-01-01

    Enzymes from extreme environments possess highly desirable traits of activity and stability for application under process conditions. One such example is l-aminoacylase (E.C. 3.5.1.14) from Thermococcus litoralis (TliACY), which catalyzes the enantioselective amide hydrolysis of N-protected l......-amino acids, useful for resolving racemic mixtures in the preparation of chiral intermediates. Variants of this enzyme with improved activity and altered substrate preference are highly desirable. We have created a structural homology model of the enzyme and applied various two different directed evolution....... The substrate preference of wild type decreases with increasingly branched and sterically hindered substrates. However, the mutant S100T/M106K disrupted this simple trend by selectively improving the substrate preference for N-benzoyl valine, with a >30-fold shift in the ratio of kcat values for N...

  11. Selection Finder (SelFi: A computational metabolic engineering tool to enable directed evolution of enzymes

    Directory of Open Access Journals (Sweden)

    Neda Hassanpour

    2017-06-01

    Full Text Available Directed evolution of enzymes consists of an iterative process of creating mutant libraries and choosing desired phenotypes through screening or selection until the enzymatic activity reaches a desired goal. The biggest challenge in directed enzyme evolution is identifying high-throughput screens or selections to isolate the variant(s with the desired property. We present in this paper a computational metabolic engineering framework, Selection Finder (SelFi, to construct a selection pathway from a desired enzymatic product to a cellular host and to couple the pathway with cell survival. We applied SelFi to construct selection pathways for four enzymes and their desired enzymatic products xylitol, D-ribulose-1,5-bisphosphate, methanol, and aniline. Two of the selection pathways identified by SelFi were previously experimentally validated for engineering Xylose Reductase and RuBisCO. Importantly, SelFi advances directed evolution of enzymes as there is currently no known generalized strategies or computational techniques for identifying high-throughput selections for engineering enzymes.

  12. Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently

    Science.gov (United States)

    Currin, Andrew; Swainston, Neil; Day, Philip J.

    2015-01-01

    The amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the ‘search space’ of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (K d) and catalytic (k cat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving k cat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the ‘best’ amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole

  13. Search for Directed Networks by Different Random Walk Strategies

    Science.gov (United States)

    Zhu, Zi-Qi; Jin, Xiao-Ling; Huang, Zhi-Long

    2012-03-01

    A comparative study is carried out on the efficiency of five different random walk strategies searching on directed networks constructed based on several typical complex networks. Due to the difference in search efficiency of the strategies rooted in network clustering, the clustering coefficient in a random walker's eye on directed networks is defined and computed to be half of the corresponding undirected networks. The search processes are performed on the directed networks based on Erdös—Rényi model, Watts—Strogatz model, Barabási—Albert model and clustered scale-free network model. It is found that self-avoiding random walk strategy is the best search strategy for such directed networks. Compared to unrestricted random walk strategy, path-iteration-avoiding random walks can also make the search process much more efficient. However, no-triangle-loop and no-quadrangle-loop random walks do not improve the search efficiency as expected, which is different from those on undirected networks since the clustering coefficient of directed networks are smaller than that of undirected networks.

  14. The evolution of unconditional strategies via the 'multiplier effect'.

    Science.gov (United States)

    McNamara, John M; Dall, Sasha R X

    2011-03-01

    Ostensibly, it makes sense in a changeable world to condition behaviour and development on information when it is available. Nevertheless, unconditional behavioural and life history strategies are widespread. Here, we show how intergenerational effects can limit the evolutionary value of responding to reliable environmental cues, and thus favour the evolutionary persistence of otherwise paradoxical unconditional strategies. While cue-ignoring genotypes do poorly in the wrong environments, in the right environment they will leave many copies of themselves, which will themselves leave many copies, and so on, leading genotypes to accumulate in habitats in which they do well. We call this 'The Multiplier Effect'. We explore the consequences of the multiplier effect by focussing on the ecologically important phenomenon of natal philopatry. We model the environment as a large number of temporally varying breeding sites connected by natal dispersal between sites. Our aim is to identify which aspects of an environment promote the multiplier effect. We show, if sites remain connected through some background level of 'accidental' dispersal, unconditional natal philopatry can evolve even when there is density dependence (with its accompanying kin competition effects), and cues that are only mildly erroneous. Thus, the multiplier effect may underpin the evolution and maintenance of unconditional strategies such as natal philopatry in many biological systems. © 2011 Blackwell Publishing Ltd/CNRS.

  15. The evolution of Soviet forces, strategy, and command

    International Nuclear Information System (INIS)

    Ball, D.; Bethe, H.A.; Blair, B.G.; Bracken, P.; Carter, A.B.; Dickinson, H.; Garwin, R.L.; Holloway, D.; Kendall, H.W.

    1988-01-01

    This paper reports on the evolution of Soviet forces, strategy and command. Soviet leaders have repeatedly emphasized that it would be tantamount to suicide to start a nuclear war. Mutual deterrence, however, does not make nuclear was impossible. The danger remains that a large-scale nuclear was could start inadvertently in an intense crisis, or by escalation out of a conventional war, or as an unforeseen combination of these. For these reasons crisis management has become a central issue in the United States, but the standard Soviet response to this Western interest has been to say that what is needed is crisis avoidance, not recipes for brinkmanship masquerading under another name. There is much sense in this view. Nevertheless, this demeanor does not mean that the Soviet Union has given no thought to the danger that a crisis might lead to nuclear war, only that Soviet categories for thinking about such matters differ from those employed in the United States

  16. Directed Evolution and Structural Characterization of a Simvastatin Synthase

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xue; Xie, Xinkai; Pashkov, Inna; Sawaya, Michael R.; Laidman, Janel; Zhang, Wenjun; Cacho, Ralph; Yeates, Todd O.; Tang, Yi; UCLA

    2010-02-02

    Enzymes from natural product biosynthetic pathways are attractive candidates for creating tailored biocatalysts to produce semisynthetic pharmaceutical compounds. LovD is an acyltransferase that converts the inactive monacolin J acid (MJA) into the cholesterol-lowering lovastatin. LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic {alpha}-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst. Here we used directed evolution to improve the properties of LovD toward semisynthesis of simvastatin. Mutants with improved catalytic efficiency, solubility, and thermal stability were obtained, with the best mutant displaying an {approx}11-fold increase in an Escherichia coli-based biocatalytic platform. To understand the structural basis of LovD enzymology, seven X-ray crystal structures were determined, including the parent LovD, an improved mutant G5, and G5 cocrystallized with ligands. Comparisons between the structures reveal that beneficial mutations stabilize the structure of G5 in a more compact conformation that is favorable for catalysis.

  17. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M.; Wong, Margaret; Kiessling, Laura L.; Steitz, Thomas A.; O’Donoghue, Patrick; Söll, Dieter

    2014-01-01

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate Nε-acetyl-Lys (AcK) onto tRNAPyl. Here, we examine an Nε-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. PMID:25385624

  18. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M; Wong, Margaret; Kiessling, Laura L; Steitz, Thomas A; O'Donoghue, Patrick; Söll, Dieter

    2014-11-25

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.

  19. Laccase engineering: from rational design to directed evolution.

    Science.gov (United States)

    Mate, Diana M; Alcalde, Miguel

    2015-01-01

    Laccases are multicopper oxidoreductases considered by many in the biotechonology field as the ultimate "green catalysts". This is mainly due to their broad substrate specificity and relative autonomy (they use molecular oxygen from air as an electron acceptor and they only produce water as by-product), making them suitable for a wide array of applications: biofuel production, bioremediation, organic synthesis, pulp biobleaching, textiles, the beverage and food industries, biosensor and biofuel cell development. Since the beginning of the 21st century, specific features of bacterial and fungal laccases have been exhaustively adapted in order to reach the industrial demands for high catalytic activity and stability in conjunction with reduced production cost. Among the goals established for laccase engineering, heterologous functional expression, improved activity and thermostability, tolerance to non-natural media (organic solvents, ionic liquids, physiological fluids) and resistance to different types of inhibitors are all challenges that have been met, while obtaining a more comprehensive understanding of laccase structure-function relationships. In this review we examine the most significant advances in this exciting research area in which rational, semi-rational and directed evolution approaches have been employed to ultimately convert laccases into high value-added biocatalysts. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Stochastic resonance and the evolution of Daphnia foraging strategy

    International Nuclear Information System (INIS)

    Dees, Nathan D; Bahar, Sonya; Moss, Frank

    2008-01-01

    Search strategies are currently of great interest, with reports on foraging ranging from albatrosses and spider monkeys to microzooplankton. Here, we investigate the role of noise in optimizing search strategies. We focus on the zooplankton Daphnia, which move in successive sequences consisting of a hop, a pause and a turn through an angle. Recent experiments have shown that their turning angle distributions (TADs) and underlying noise intensities are similar across species and age groups, suggesting an evolutionary origin of this internal noise. We explore this hypothesis further with a digital simulation (EVO) based solely on the three central Darwinian themes: inheritability, variability and survivability. Separate simulations utilizing stochastic resonance (SR) indicate that foraging success, and hence fitness, is maximized at an optimum TAD noise intensity, which is represented by the distribution's characteristic width, σ. In both the EVO and SR simulations, foraging success is the criterion, and the results are the predicted characteristic widths of the TADs that maximize success. Our results are twofold: (1) the evolving characteristic widths achieve stasis after many generations; (2) as a hop length parameter is changed, variations in the evolved widths generated by EVO parallel those predicted by SR. These findings provide support for the hypotheses that (1) σ is an evolved quantity and that (2) SR plays a role in evolution. (communication)

  1. Vocabulary Acquisition through Direct and Indirect Learning Strategies

    Science.gov (United States)

    Naeimi, Maki; Foo, Thomas Chow Voon

    2015-01-01

    Vocabulary learning has long been considered as one of the essential components for developing language learning. However, language learners are required to not just concern about memorizing definitions but also integrating vocabulary meaning into their present knowledge. Many strategies such as direct or indirect ones may be integrated to enhance…

  2. Effects of Direct and Indirect Instructional Strategies on Students ...

    African Journals Online (AJOL)

    This is a quasi experimental research designed to determine the effects of Direct and Indirect instructional strategies on Mathematics achievement among junior secondary school students. The population consisted of students in a Public Secondary School in Owerri, Imo State. A sample of 102 students from two (2) intact ...

  3. A model of directional selection applied to the evolution of drug resistance in HIV-1.

    Science.gov (United States)

    Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

    2007-04-01

    Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

  4. Battery parameterisation based on differential evolution via a boundary evolution strategy

    Science.gov (United States)

    Yang, Guangya

    2014-01-01

    Attention has been given to the battery modelling in the electric engineering field following the current development of renewable energy and electrification of transportation. The establishment of the equivalent circuit model of the battery requires data preparation and parameterisation. Besides, as the equivalent circuit model is an abstract map of the battery electric characteristics, the determination of the possible ranges of parameters can be a challenging task. In this paper, an efficient yet easy to implement method is proposed to parameterise the equivalent circuit model of batteries utilising the advances of evolutionary algorithms (EAs). Differential evolution (DE) is selected and modified to parameterise an equivalent circuit model of lithium-ion batteries. A boundary evolution strategy (BES) is developed and incorporated into the DE to update the parameter boundaries during the parameterisation. The method can parameterise the model without extensive data preparation. In addition, the approach can also estimate the initial SOC and the available capacity. The efficiency of the approach is verified through two battery packs, one is an 8-cell battery module and one from an electrical vehicle.

  5. Direct harmonic voltage control strategy for shunt active power filter

    DEFF Research Database (Denmark)

    Munir, Hafiz Mudassir; Zou, JianXiao; Xie, Chuan

    2017-01-01

    generation system (DPGS) where the nonlinear loads are highly dispersed. Local harmonic voltage detection based Resistive-APF (R-APF) seems more suitable to be applied in the DPGS, however, R-APF suffers from poor compensation performance and difficulty of parameter tuning. In this paper, a direct harmonic...... voltage control strategy for the S-APF is proposed with local point of common coupling (PCC) voltage detection only. The control strategy design procedure is given in detail. Simulation is conducted in Matlab/Simulink to compare the performance between the R-APF and the proposed method. The results...

  6. Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) for directed enzyme evolution.

    Science.gov (United States)

    Gonzalez-Perez, David; Molina-Espeja, Patricia; Garcia-Ruiz, Eva; Alcalde, Miguel

    2014-01-01

    Approaches that depend on directed evolution require reliable methods to generate DNA diversity so that mutant libraries can focus on specific target regions. We took advantage of the high frequency of homologous DNA recombination in Saccharomyces cerevisiae to develop a strategy for domain mutagenesis aimed at introducing and in vivo recombining random mutations in defined segments of DNA. Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) is a one-pot random mutagenic method for short protein regions that harnesses the in vivo recombination apparatus of yeast. Using this approach, libraries can be prepared with different mutational loads in DNA segments of less than 30 amino acids so that they can be assembled into the remaining unaltered DNA regions in vivo with high fidelity. As a proof of concept, we present two eukaryotic-ligninolytic enzyme case studies: i) the enhancement of the oxidative stability of a H2O2-sensitive versatile peroxidase by independent evolution of three distinct protein segments (Leu28-Gly57, Leu149-Ala174 and Ile199-Leu268); and ii) the heterologous functional expression of an unspecific peroxygenase by exclusive evolution of its native 43-residue signal sequence.

  7. Intrasexual competition facilitates the evolution of alternative mating strategies in a colour polymorphic fish.

    Science.gov (United States)

    Hurtado-Gonzales, Jorge L; Uy, J Albert C

    2010-12-23

    Intense competition for access to females can lead to males exploiting different components of sexual selection, and result in the evolution of alternative mating strategies (AMSs). Males of Poecilia parae, a colour polymorphic fish, exhibit five distinct phenotypes: drab-coloured (immaculata), striped (parae), structural-coloured (blue) and carotenoid-based red and yellow morphs. Previous work indicates that immaculata males employ a sneaker strategy, whereas the red and yellow morphs exploit female preferences for carotenoid-based colours. Mating strategies favouring the maintenance of the other morphs remain to be determined. Here, we report the role of agonistic male-male interactions in influencing female mating preferences and male mating success, and in facilitating the evolution of AMSs. Our study reveals variation in aggressiveness among P. parae morphs during indirect and direct interactions with sexually receptive females. Two morphs, parae and yellow, use aggression to enhance their mating success (i.e., number of copulations) by 1) directly monopolizing access to females, and 2) modifying female preferences after winning agonistic encounters. Conversely, we found that the success of the drab-coloured immaculata morph, which specializes in a sneak copulation strategy, relies in its ability to circumvent both male aggression and female choice when facing all but yellow males. Strong directional selection is expected to deplete genetic variation, yet many species show striking genetically-based polymorphisms. Most studies evoke frequency dependent selection to explain the persistence of such variation. Consistent with a growing body of evidence, our findings suggest that a complex form of balancing selection may alternatively explain the evolution and maintenance of AMSs in a colour polymorphic fish. In particular, this study demonstrates that intrasexual competition results in phenotypically distinct males exhibiting clear differences in their levels of

  8. Intrasexual competition facilitates the evolution of alternative mating strategies in a colour polymorphic fish

    Directory of Open Access Journals (Sweden)

    Uy J Albert C

    2010-12-01

    Full Text Available Abstract Background Intense competition for access to females can lead to males exploiting different components of sexual selection, and result in the evolution of alternative mating strategies (AMSs. Males of Poecilia parae, a colour polymorphic fish, exhibit five distinct phenotypes: drab-coloured (immaculata, striped (parae, structural-coloured (blue and carotenoid-based red and yellow morphs. Previous work indicates that immaculata males employ a sneaker strategy, whereas the red and yellow morphs exploit female preferences for carotenoid-based colours. Mating strategies favouring the maintenance of the other morphs remain to be determined. Here, we report the role of agonistic male-male interactions in influencing female mating preferences and male mating success, and in facilitating the evolution of AMSs. Results Our study reveals variation in aggressiveness among P. parae morphs during indirect and direct interactions with sexually receptive females. Two morphs, parae and yellow, use aggression to enhance their mating success (i.e., number of copulations by 1 directly monopolizing access to females, and 2 modifying female preferences after winning agonistic encounters. Conversely, we found that the success of the drab-coloured immaculata morph, which specializes in a sneak copulation strategy, relies in its ability to circumvent both male aggression and female choice when facing all but yellow males. Conclusions Strong directional selection is expected to deplete genetic variation, yet many species show striking genetically-based polymorphisms. Most studies evoke frequency dependent selection to explain the persistence of such variation. Consistent with a growing body of evidence, our findings suggest that a complex form of balancing selection may alternatively explain the evolution and maintenance of AMSs in a colour polymorphic fish. In particular, this study demonstrates that intrasexual competition results in phenotypically distinct

  9. Strategic Directions for the Bucharest Strategy and City Brand

    Directory of Open Access Journals (Sweden)

    Ana-Claudia Ţapardel

    2012-11-01

    Full Text Available On the international stage, public administration has become an essential factor, capable of providing a nation with the competitive advantage. Improving standards in local administration in our country has included not only a vigorous and sustained process of reform, but also a drive to modernise and perfect management within the public sector. These aspects are essential, since decisions made by partners and investors are to an ever larger extent influenced by the quality, efficiency and credibility of public administration. Following these considerations, and based upon an empirical research conducted with the aid of a survey and a comparative analysis between the manner in which the branding and development strategies were developed in Vancouver and Bucharest, the present paper aims to identify the main strategic directions and branding elements necessary in elaborating a strategy and in accumulating a dossier of best practices, in order to implement successfully the strategic planning process and the branding strategy in the local communities of Romania.

  10. THE EVOLUTION AND EFFECTS OF THE FOREIGN DIRECT INVESTMENTS IN ROMANIA

    Directory of Open Access Journals (Sweden)

    DOBROTĂ GABRIELA

    2014-02-01

    Full Text Available Foreign direct investments are an important component of financial resources needed for the development of any economy. Attract them should represent a desideratum in economic development strategies, fact which requires providing a favorable climate, generated by a set of economic, political, social or legal conditions. The effects generated by FDI at the macroeconomic level, are reported in plan of economic growth, at the level of balance of payments and the state budget, and also on the labor market. In the paper are presented aspects of the process of attracting FDI in Romania after the transition to market economy and is realized a meaningful analysis of flows and corresponding balances between 2003-2012. The research has enabled the formulation of important conclusions regarding the evolution of FDI, their effects and the favorable conditions for their assimilation in the romanian economy.

  11. Direct approach for solving nonlinear evolution and two-point

    Indian Academy of Sciences (India)

    Time-delayed nonlinear evolution equations and boundary value problems have a wide range of applications in science and engineering. In this paper, we implement the differential transform method to solve the nonlinear delay differential equation and boundary value problems. Also, we present some numerical examples ...

  12. Availability of public goods shapes the evolution of competing metabolic strategies.

    Science.gov (United States)

    Bachmann, Herwig; Fischlechner, Martin; Rabbers, Iraes; Barfa, Nakul; Branco dos Santos, Filipe; Molenaar, Douwe; Teusink, Bas

    2013-08-27

    Tradeoffs provide a rationale for the outcome of natural selection. A prominent example is the negative correlation between the growth rate and the biomass yield in unicellular organisms. This tradeoff leads to a dilemma, where the optimization of growth rate is advantageous for an individual, whereas the optimization of the biomass yield would be advantageous for a population. High-rate strategies are observed in a broad variety of organisms such as Escherichia coli, yeast, and cancer cells. Growth in suspension cultures favors fast-growing organisms, whereas spatial structure is of importance for the evolution of high-yield strategies. Despite this realization, experimental methods to directly select for increased yield are lacking. We here show that the serial propagation of a microbial population in a water-in-oil emulsion allows selection of strains with increased biomass yield. The propagation in emulsion creates a spatially structured environment where the growth-limiting substrate is privatized for populations founded by individual cells. Experimental evolution of several isogenic Lactococcus lactis strains demonstrated the existence of a tradeoff between growth rate and biomass yield as an apparent Pareto front. The underlying mutations altered glucose transport and led to major shifts between homofermentative and heterofermentative metabolism, accounting for the changes in metabolic efficiency. The results demonstrated the impact of privatizing a public good on the evolutionary outcome between competing metabolic strategies. The presented approach allows the investigation of fundamental questions in biology such as the evolution of cooperation, cell-cell interactions, and the relationships between environmental and metabolic constraints.

  13. Directed evolution of an extremely stable fluorescent protein.

    Science.gov (United States)

    Kiss, Csaba; Temirov, Jamshid; Chasteen, Leslie; Waldo, Geoffrey S; Bradbury, Andrew R M

    2009-05-01

    In this paper we describe the evolution of eCGP123, an extremely stable green fluorescent protein based on a previously described fluorescent protein created by consensus engineering (CGP: consensus green protein). eCGP123 could not be denatured by a standard thermal melt, preserved almost full fluorescence after overnight incubation at 80 degrees C and possessed a free energy of denaturation of 12.4 kcal/mol. It was created from CGP by a recursive process involving the sequential introduction of three destabilizing heterologous inserts, evolution to overcome the destabilization and finally 'removal' of the destabilizing insert by gene synthesis. We believe that this approach may be generally applicable to the stabilization of other proteins.

  14. The Explicit Instruction of Reading Strategies: Directed Reading Thinking Activity vs. Guided Reading Strategies

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Yazdani

    2015-05-01

    Full Text Available Investigating the efficiencies and deficiencies of reading strategies is one of the noticeable issues in the related theory and research in reading comprehension instruction. This study was to examine the impact of Directed Reading Thinking Activity (DRTA and Guided Reading (GR on reading comprehension. Sixty three Iranian students of grade one in Shahed high school in the city of Bojnourd took part in the study. They were assigned in three groups, one control and two experimental groups. The instruction lasted for ten weeks. This study utilized a pretest posttest control group in quantitative quasi- experimental design. The same reading comprehension test was administered as pre-test and post-test. The results were twofold: First, the instruction of learning strategies could foster reading comprehension skill. Second, while the explicit instruction of both strategies could improve the students' reading comprehension skill, Directed Reading Thinking Activity had a more significant positive effect than Guided Reading.

  15. Direct and indirect welfare chauvinism as party strategies

    DEFF Research Database (Denmark)

    Careja, Romana; Elmelund-Præstekær, Christian; Klitgaard, Michael Baggesen

    2016-01-01

    welfare chauvinism occurs as a result of legislative changes that explicitly exclude recipients from social protection or reduce the level thereof on the basis of ethnicity. Indirect welfare chauvinism is the result of policy measures that apply to both natives and immigrants, but which deliberately...... and deliberate policy-making strategies of the party. It shows that the distinction between direct and indirect chauvinism is a useful theoretical tool for understanding how the Danish People's Party can fulfill the expectations of both its electorate and its coalition partners, even if they point in different...

  16. Direct and indirect welfare chauvinism as party strategies

    DEFF Research Database (Denmark)

    Careja, Romana; Elmelund-Præstekær, Christian; Klitgaard, Michael Baggesen

    2016-01-01

    negatively affect immigrants the most. Combining quantitative and qualitative analysis of labour market reforms in Denmark, where one of the most successful populist right-wing parties in Europe – the Danish People's Party – held a pivotal position in the period 2001–11, the article traces the intentions...... and deliberate policy-making strategies of the party. It shows that the distinction between direct and indirect chauvinism is a useful theoretical tool for understanding how the Danish People's Party can fulfill the expectations of both its electorate and its coalition partners, even if they point in different...

  17. Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Zong Sheng Guo

    2017-05-01

    Full Text Available The concept of oncolytic virus (OV-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance. Second, OVs may be armed to express Th1-stimulatory cytokines/chemokines or costimulators to recruit and sustain the potent antitumor immunity into the TME to focus their therapeutic activity within the sites of disease. Third, combinations of OV with immunomodulatory drugs or antibodies that recondition the TME have proven to be highly promising in early studies. Fourth, combinations of OVs with other immunotherapeutic regimens (such as prime-boost cancer vaccines, CAR T cells; armed with bispecific T-cell engagers have also yielded promising preliminary findings. Finally, OVs have been combined with immune checkpoint blockade, with robust antitumor efficacy being observed in pilot evaluations. Despite some expected hurdles for the rapid translation of OV-based state-of-the-art protocols, we believe that a cohort of these novel approaches will join the repertoire of standard cancer treatment options in the near future.

  18. Effort Flow Analysis: A Methodology for Directed Product Evolution Using Rigid Body and Compliant Mechanisms

    National Research Council Canada - National Science Library

    Greer, James

    2002-01-01

    This dissertation presents a systematic design methodology for directed product evolution that uses both rigid body and compliant mechanisms to facilitate component combination in the domain of mechanical products...

  19. Evolution of quantum and classical strategies on networks by group interactions

    International Nuclear Information System (INIS)

    Li Qiang; Chen Minyou; Iqbal, Azhar; Abbott, Derek

    2012-01-01

    In this paper, quantum strategies are introduced within evolutionary games in order to investigate the evolution of quantum and classical strategies on networks in the public goods game. Comparing the results of evolution on a scale-free network and a square lattice, we find that a quantum strategy outperforms the classical strategies, regardless of the network. Moreover, a quantum strategy dominates the population earlier in group interactions than it does in pairwise interactions. In particular, if the hub node in a scale-free network is occupied by a cooperator initially, the strategy of cooperation will prevail in the population. However, in other situations, a quantum strategy can defeat the classical ones and finally becomes the dominant strategy in the population. (paper)

  20. Engineering 7β-Hydroxysteroid Dehydrogenase for Enhanced Ursodeoxycholic Acid Production by Multiobjective Directed Evolution.

    Science.gov (United States)

    Zheng, Ming-Min; Chen, Ke-Cai; Wang, Ru-Feng; Li, Hao; Li, Chun-Xiu; Xu, Jian-He

    2017-02-15

    Ursodeoxycholic acid (UDCA) is the main active ingredient of natural bear bile powder with multiple pharmacological functions. 7β-Hydroxysteroid dehydrogenase (HSDH) is a key biocatalyst for the synthesis of UDCA. However, all the 7β-HSDHs reported commonly suffer from poor activity and thermostability, resulting in limited productivity of UDCA. In this study, a multiobjective directed evolution (MODE) strategy was proposed and applied to improve the activity, thermostability, and pH optimum of a 7β-HSDH. The best variant (V 3-1 ) showed a specific activity 5.5-fold higher than and a half-life 3-fold longer than those of the wild type. In addition, the pH optimum of the variant was shifted to a weakly alkaline value. In the cascade reaction, the productivity of UDCA with V 3-1 increased to 942 g L -1 day -1 , in contrast to 141 g L -1 day -1 with the wild type. Therefore, this study provides a useful strategy for improving the catalytic efficiency of a key enzyme that significantly facilitated the bioproduction of UDCA.

  1. The evolution of physician-directed managed care.

    Science.gov (United States)

    Unland, J J

    1995-01-01

    The health care industry is evolving. In the near term, POs will become the state of the art in physician-directed managed care. Eventually, POs will merge into fully integrated group practices. From there, regional POs and group practices will develop their own insurance products. But because these organizations will be dominated by physicians who wish to practice medicine, rather than sell insurance, money will be made by appropriately managing risk and providing high-quality care. In time, physicians will take control and "manage" managed care, as they are the only ones--not administrators, executives, or other business people--who are in a position to fundamentally revise the way medicine is practiced.

  2. Evolution of strategies to improve preclinical cardiac safety testing.

    Science.gov (United States)

    Gintant, Gary; Sager, Philip T; Stockbridge, Norman

    2016-07-01

    The early and efficient assessment of cardiac safety liabilities is essential to confidently advance novel drug candidates. This article discusses evolving mechanistically based preclinical strategies for detecting drug-induced electrophysiological and structural cardiotoxicity using in vitro human ion channel assays, human-based in silico reconstructions and human stem cell-derived cardiomyocytes. These strategies represent a paradigm shift from current approaches, which rely on simplistic in vitro assays that measure blockade of the Kv11.1 current (also known as the hERG current or IKr) and on the use of non-human cells or tissues. These new strategies have the potential to improve sensitivity and specificity in the early detection of genuine cardiotoxicity risks, thereby reducing the likelihood of mistakenly discarding viable drug candidates and speeding the progression of worthy drugs into clinical trials.

  3. The evolution of trade-offs under directional and correlational selection.

    Science.gov (United States)

    Roff, Derek A; Fairbairn, Daphne J

    2012-08-01

    Using quantitative genetic theory, we develop predictions for the evolution of trade-offs in response to directional and correlational selection. We predict that directional selection favoring an increase in one trait in a trade-off will result in change in the intercept but not the slope of the trade-off function, with the mean value of the selected trait increasing and that of the correlated trait decreasing. Natural selection will generally favor an increase in some combination of trait values, which can be represented as directional selection on an index value. Such selection induces both directional and correlational selection on the component traits. Theory predicts that selection on an index value will also change the intercept but not the slope of the trade-off function but because of correlational selection, the direction of change in component traits may be in the same or opposite directions. We test these predictions using artificial selection on the well-established trade-off between fecundity and flight capability in the cricket, Gryllus firmus and compare the empirical results with a priori predictions made using genetic parameters from a separate half-sibling experiment. Our results support the predictions and illustrate the complexity of trade-off evolution when component traits are subject to both directional and correlational selection. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  4. The evolution of Islamic State's strategy | Solomon | Scientia Militaria ...

    African Journals Online (AJOL)

    With these funds, IS has deployed soft power – digging sewage systems and providing stipends to families – to earn the loyalty of its 'citizens'. IS has also displayed superior military strategy combining conventional military doctrine with asymmetric warfare. As IS are confronted with superior conventional forces in their ...

  5. Evolution of complex asexual reproductive strategies in jellyfish

    DEFF Research Database (Denmark)

    Schnedler-Meyer, Nicolas Azaña; Pigolotti, Simone; Mariani, Patrizio

    2018-01-01

    Many living organisms in terrestrial and aquatic ecosystems rely on multiple reproductive strategies to reduce the risk of extinction in variable environments. Examples are provided by the polyp stage of several bloom-forming jellyfish species, which can reproduce asexually using different buddin...

  6. Agent Based Simulation of Group Emotions Evolution and Strategy Intervention in Extreme Events

    Directory of Open Access Journals (Sweden)

    Bo Li

    2014-01-01

    Full Text Available Agent based simulation method has become a prominent approach in computational modeling and analysis of public emergency management in social science research. The group emotions evolution, information diffusion, and collective behavior selection make extreme incidents studies a complex system problem, which requires new methods for incidents management and strategy evaluation. This paper studies the group emotion evolution and intervention strategy effectiveness using agent based simulation method. By employing a computational experimentation methodology, we construct the group emotion evolution as a complex system and test the effects of three strategies. In addition, the events-chain model is proposed to model the accumulation influence of the temporal successive events. Each strategy is examined through three simulation experiments, including two make-up scenarios and a real case study. We show how various strategies could impact the group emotion evolution in terms of the complex emergence and emotion accumulation influence in extreme events. This paper also provides an effective method of how to use agent-based simulation for the study of complex collective behavior evolution problem in extreme incidents, emergency, and security study domains.

  7. Evolution and Morphogenesis of Simulated Modular Robots: A Comparison Between a Direct and Generative Encoding

    DEFF Research Database (Denmark)

    Veenstra, Frank; Faina, Andres; Risi, Sebastian

    2017-01-01

    Modular robots oer an important benet in evolutionary robotics, which is to quickly evaluate evolved morphologies and control systems in reality. However, articial evolution of simulated modular robotics is a dicult and time consuming task requiring signicant computational power. While articial...... evolution in virtual creatures has made use of powerful generative encodings, here we investigate how a generative encoding and direct encoding compare for the evolution of locomotion in modular robots when the number of robotic modules changes. Simulating less modules would decrease the size of the genome...

  8. An evolution-based strategy for engineering allosteric regulation

    Science.gov (United States)

    Pincus, David; Resnekov, Orna; Reynolds, Kimberly A.

    2017-04-01

    Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach—termed rational engineering of allostery at conserved hotspots (REACH)—to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure. REACH entails the use of statistical coupling analysis (SCA) to identify ‘allosteric hotspots’ on protein surfaces, the development and implementation of experimental assays to test hotspots for functionality, and a toolkit of allosteric modulators to impinge on endogenous cellular circuitry. REACH can be broadly applied to rewire cellular processes to respond to novel inputs.

  9. Evolution in Clinical Knowledge Management Strategy at Intermountain Healthcare

    Science.gov (United States)

    Hulse, Nathan C.; Galland, Joel; Borsato, Emerson P.

    2012-01-01

    In this manuscript, we present an overview of the clinical knowledge management strategy at Intermountain Healthcare in support of our electronic medical record systems. Intermountain first initiated efforts in developing a centralized enterprise knowledge repository in 2001. Applications developed, areas of emphasis served, and key areas of focus are presented. We also detail historical and current areas of emphasis, in response to business needs. PMID:23304309

  10. A roadmap to directed enzyme evolution and screening systems for biotechnological applications

    Directory of Open Access Journals (Sweden)

    Ronny Martínez

    2013-01-01

    Full Text Available Enzymes have been long used in man-made biochemical processes, from brewing and fermentation to current industrial production of fine chemicals. The ever-growing demand for enzymes in increasingly specific applications requires tailoring naturally occurring enzymes to the non-natural conditions found in industrial processes. Relationships between enzyme sequence, structure and activity are far from understood, thus hindering the capacity to design tailored biocatalysts. In the field of protein engineering, directed enzyme evolution is a powerful algorithm to generate and identify novel and improved enzymes through iterative rounds of mutagenesis and screening applying a specific evolutive pressure. In practice, critical checkpoints in directed evolution are: selection of the starting point, generation of the mutant library, development of the screening assay and analysis of the output of the screening campaign. Each step in directed evolution can be performed using conceptually and technically different approaches, all having inherent advantages and challenges. In this article, we present and discuss in a general overview, challenges of designing and performing a directed enzyme evolution campaign, current advances in methods, as well as highlighting some examples of its applications in industrially relevant enzymes.

  11. Effect of direct contact with iron on gas evolution behavior of aluminum

    International Nuclear Information System (INIS)

    Hashizume, Shuji; Matsumoto, Junko; Banba, Tsunetaka

    1998-01-01

    Dry Low-Level Radioactive Waste (LLW), incombustible solid LLW, generated from nuclear power stations is planed to be solidified with cement backfill in drums. The solidified dry LLW will be buried to shallow underground at Rokkasyo LLW Disposal Center. It is well known that corrosion of aluminum and hydrogen gas evolution occur in high pH environments such as mortar. Gas evolution from aluminum is likely to effect the leachability of solidified dry LLW with mortar. Though aluminum removal from dry LLW is planed, a small amount of aluminum will be actually included in dry LLW. Large effects of pH and temperature on corrosion rate of aluminum and gas evolution were recognized in our previous study. It was also found that 1.5 mole hydrogen gas evolves while 1 mole aluminum corrodes under 60degC. Actually aluminum in drums is likely to contact with carbon steel of which main element is iron. The gas evolution behavior of aluminum is expected to be affected by its direct contact with iron. Therefore, effect of direct contact with iron on gas evolution behavior of aluminum was studied. The corrosion rate of aluminum increased by contacting it with iron in simulating mortar environments. The amount of gas evolution from aluminum was reduced by contacting with iron. The reduction in gas evolution was considered to result from the change of cathode reaction from hydrogen evolution to oxygen reduction. When aluminum contacts with iron, the corrosion and gas evolution behavior of aluminum is significantly affected oxygen in environment. (author)

  12. Directed evolution and in silico analysis of reaction centre proteins reveal molecular signatures of photosynthesis adaptation to radiation pressure.

    Directory of Open Access Journals (Sweden)

    Giuseppina Rea

    2011-01-01

    Full Text Available Evolutionary mechanisms adopted by the photosynthetic apparatus to modifications in the Earth's atmosphere on a geological time-scale remain a focus of intense research. The photosynthetic machinery has had to cope with continuously changing environmental conditions and particularly with the complex ionizing radiation emitted by solar flares. The photosynthetic D1 protein, being the site of electron tunneling-mediated charge separation and solar energy transduction, is a hot spot for the generation of radiation-induced radical injuries. We explored the possibility to produce D1 variants tolerant to ionizing radiation in Chlamydomonas reinhardtii and clarified the effect of radiation-induced oxidative damage on the photosynthetic proteins evolution. In vitro directed evolution strategies targeted at the D1 protein were adopted to create libraries of chlamydomonas random mutants, subsequently selected by exposures to radical-generating proton or neutron sources. The common trend observed in the D1 aminoacidic substitutions was the replacement of less polar by more polar amino acids. The applied selection pressure forced replacement of residues more sensitive to oxidative damage with less sensitive ones, suggesting that ionizing radiation may have been one of the driving forces in the evolution of the eukaryotic photosynthetic apparatus. A set of the identified aminoacidic substitutions, close to the secondary plastoquinone binding niche and oxygen evolving complex, were introduced by site-directed mutagenesis in un-transformed strains, and their sensitivity to free radicals attack analyzed. Mutants displayed reduced electron transport efficiency in physiological conditions, and increased photosynthetic performance stability and oxygen evolution capacity in stressful high-light conditions. Finally, comparative in silico analyses of D1 aminoacidic sequences of organisms differently located in the evolution chain, revealed a higher ratio of residues

  13. The evolution of intellectual property strategy in innovation ecosystems

    DEFF Research Database (Denmark)

    Holgersson, Marcus; Granstrand, Ove; Bogers, Marcel

    2018-01-01

    In this article, we attempt to extend and nuance the debate on intellectual property (IP) strategy, appropriation, and open innovation in dynamic and systemic innovation contexts. We present the case of four generations of mobile telecommunications systems (covering the period 1980-2015), and des......In this article, we attempt to extend and nuance the debate on intellectual property (IP) strategy, appropriation, and open innovation in dynamic and systemic innovation contexts. We present the case of four generations of mobile telecommunications systems (covering the period 1980...... and technologies to benefit from openness and appropriation of innovation. Our analysis shows that the discussion of competitiveness and appropriability needs to be expanded from the focal appropriability regime and complementary assets to the larger context of the innovation ecosystem and its cooperative...... and competitive actor relations, with dispersed complementary and substitute assets and technologies. Consequently, the shaping of complementary and substitute appropriability regimes is central when strategizing in dynamic and systemic innovation contexts. This holds important implications for the management...

  14. Role of environmental variability in the evolution of life history strategies.

    Science.gov (United States)

    Hastings, A; Caswell, H

    1979-09-01

    We reexamine the role of environmental variability in the evolution of life history strategies. We show that normally distributed deviations in the quality of the environment should lead to normally distributed deviations in the logarithm of year-to-year survival probabilities, which leads to interesting consequences for the evolution of annual and perennial strategies and reproductive effort. We also examine the effects of using differing criteria to determine the outcome of selection. Some predictions of previous theory are reversed, allowing distinctions between r and K theory and a theory based on variability. However, these distinctions require information about both the environment and the selection process not required by current theory.

  15. The evolution of phenotypic integration: How directional selection reshapes covariation in mice.

    Science.gov (United States)

    Penna, Anna; Melo, Diogo; Bernardi, Sandra; Oyarzabal, Maria Inés; Marroig, Gabriel

    2017-10-01

    Variation is the basis for evolution, and understanding how variation can evolve is a central question in biology. In complex phenotypes, covariation plays an even more important role, as genetic associations between traits can bias and alter evolutionary change. Covariation can be shaped by complex interactions between loci, and this genetic architecture can also change during evolution. In this article, we analyzed mouse lines experimentally selected for changes in size to address the question of how multivariate covariation changes under directional selection, as well as to identify the consequences of these changes to evolution. Selected lines showed a clear restructuring of covariation in their cranium and, instead of depleting their size variation, these lines increased their magnitude of integration and the proportion of variation associated with the direction of selection. This result is compatible with recent theoretical works on the evolution of covariation that take the complexities of genetic architecture into account. This result also contradicts the traditional view of the effects of selection on available covariation and suggests a much more complex view of how populations respond to selection. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  16. Degeneration and domestication of a selfish gene in yeast: molecular evolution versus site-directed mutagenesis.

    Science.gov (United States)

    Koufopanou, Vassiliki; Burt, Austin

    2005-07-01

    VDE is a homing endonuclease gene in yeasts with an unusual evolutionary history including horizontal transmission, degeneration, and domestication into the mating-type switching locus HO. We investigate here the effects of these features on its molecular evolution. In addition, we correlate rates of evolution with results from site-directed mutagenesis studies. Functional elements have lower rates of evolution than degenerate ones and higher conservation at functionally important sites. However, functionally important and unimportant sites are equally likely to have been involved in the evolution of new function during the domestication of VDE into HO. The domestication event also indicates that VDE has been lost in some species and that VDE has been present in yeasts for more than 50 Myr.

  17. Evolution of double white dwarf binaries undergoing direct-impact accretion: Implications for gravitational wave astronomy

    Science.gov (United States)

    Kremer, Kyle; Breivik, Katelyn; Larson, Shane L.; Kalogera, Vassiliki

    2017-01-01

    For close double white dwarf binaries, the mass-transfer phenomenon known as direct-impact accretion (when the mass transfer stream impacts the accretor directly rather than forming a disc) may play a pivotal role in the long-term evolution of the systems. In this analysis, we explore the long-term evolution of white dwarf binaries accreting through direct-impact and explore implications of such systems to gravitational wave astronomy. We cover a broad range of parameter space which includes initial component masses and the strength of tidal coupling, and show that these systems, which lie firmly within the LISA frequency range, show strong negative chirps which can last as long as several million years. Detections of double white dwarf systems in the direct-impact phase by detectors such as LISA would provide astronomers with unique ways of probing the physics governing close compact object binaries.

  18. BIOINSPIRED DESIGN AND DIRECTED EVOLUTION OF IRON CONTAINING ENZYMES FOR GREENSYNTHETIC PROCESSES AND BIOREMEDIATION

    Science.gov (United States)

    SU833912Title: Bioinspired Design and Directed Evolution of Iron Containing Enzymes for Green Synthetic Processes and BioremediationEdward I. Solomon, Shaun D. Wong, Lei Liu, Caleb B. Bell, IIICynthia Nolt-HelmsProject Period: August 15, 2008 - August 14,...

  19. The Evolution of Cost/Schedule Control (Direct Labor) in Naval Shipyards

    National Research Council Canada - National Science Library

    Gessis, Scott N

    1992-01-01

    The evolution of a Cost/Schedule Control System (C/SCS), for direct labor, in naval shipyards can be traced from the cost/schedule control concept used in the Air Force in the 1960s, as an initiative toward more reliable data...

  20. Advances in directed monooxygenase evolution : from diversity generation and flow cytometry screening to tailor-made monooxygenases

    OpenAIRE

    Ruff, Anna Joëlle

    2012-01-01

    Directed Evolution became a powerful tool for proteins engineers to generate tailor-made biocatalyst. Directed protein evolution consist of the following three consecutive main steps, which are performed in iterative cycles; Step 1 the gene diversity generation, Step 2 the screening for improved variants and Step 3 the isolation of gene encoding for improved proteins. In this thesis, methodological advancements in the two key steps of the directed evolution, the diversity generation (SeSaM me...

  1. Developing Marketing Higher Education Strategies Based on Students’ Satisfaction Evolution

    Directory of Open Access Journals (Sweden)

    Andreea Orîndaru

    2015-09-01

    Full Text Available The educational system worldwide is currently under the spotlight as it shows significant signs of an ongoing crisis in its search for resources, visibility in the crowded market and significance to the ever-changing society. Within this framework, higher education institutions (HEIs are taking significant actions for maintaining students as clients of their educational services. As competition on this market is becoming stronger, HEIs face difficulties in keeping students, leading them to a continuous evaluation of student satisfaction indicators. Beyond HEIs’ managers, researchers in marketing higher education have contributed to the development of a comprehensive literature where still very few have forwarded a longitudinal research model for student satisfaction evaluation despite the need for such approaches. Given this context, the current paper presents a first step towards a longitudinal study as it displays, in a compare and contrast vision, the results of two different quantitative research projects developed in the same student community, with the same objective, but conducted in two different years. Among the most significant results of this research refer to an important decline in students’ satisfaction with a significant increase in the number of students that have a neutral perception. This is highly expected to determine a major impact on university’s overall performance and, therefore, it constitutes a strong argument for determining underlying causes, and especially developing the appropriate marketing strategies to tackle with these issues. Based on this result and other similar research outcomes, strategic and tactic recommendations are granted in the final part of this paper.

  2. Promotional Strategies Direct Marketing and Technological Innovations in Banking

    OpenAIRE

    Valeria Arina BALACEANU

    2011-01-01

    Modern advertising strategies involve the use of a bank's media and consumer incentives, so that banking institution, and thus offer products/services to cause favorable changes in mentality and their consumption habits, also important is the establishment an effective communication with employees, shareholders, competitors. Promotion strategies are essential to business success. Success is guaranteed if the message is sent to the right people at the right time. Promotion has a special place ...

  3. Money laundering in Dubai: strategies and future directions

    OpenAIRE

    Belaisha, Belaisha; Brooks, Graham

    2014-01-01

    Purpose\\ud – This paper aims to highlight present strategies to prevent money laundering in Dubai.\\ud \\ud Design/methodology/approach\\ud – Thirty semi-structured interviews were conducted with Anti Money Laundering Suspicion Cases Unit (AMLSCU), Anti Organized Crime Department (AOCD) and Central Bank employees.\\ud \\ud Findings\\ud – This paper shows that AMLSCU, AOCD and Central Bank employees are aware that future strategies to prevent money laundering are needed.\\ud \\ud Research limitations/...

  4. Cloud computing task scheduling strategy based on improved differential evolution algorithm

    Science.gov (United States)

    Ge, Junwei; He, Qian; Fang, Yiqiu

    2017-04-01

    In order to optimize the cloud computing task scheduling scheme, an improved differential evolution algorithm for cloud computing task scheduling is proposed. Firstly, the cloud computing task scheduling model, according to the model of the fitness function, and then used improved optimization calculation of the fitness function of the evolutionary algorithm, according to the evolution of generation of dynamic selection strategy through dynamic mutation strategy to ensure the global and local search ability. The performance test experiment was carried out in the CloudSim simulation platform, the experimental results show that the improved differential evolution algorithm can reduce the cloud computing task execution time and user cost saving, good implementation of the optimal scheduling of cloud computing tasks.

  5. Mixed-integer evolution strategies for parameter optimization and their applications to medical image analysis

    NARCIS (Netherlands)

    Li, Rui

    2009-01-01

    The target of this work is to extend the canonical Evolution Strategies (ES) from traditional real-valued parameter optimization domain to mixed-integer parameter optimization domain. This is necessary because there exist numerous practical optimization problems from industry in which the set of

  6. Teaching evolution (and all of biology) more effectively: Strategies for engagement, critical reasoning, and confronting misconceptions.

    Science.gov (United States)

    Nelson, Craig E

    2008-08-01

    The strength of the evidence supporting evolution has increased markedly since the discovery of DNA but, paradoxically, public resistance to accepting evolution seems to have become stronger. A key dilemma is that science faculty have often continued to teach evolution ineffectively, even as the evidence that traditional ways of teaching are inferior has become stronger and stronger. Three pedagogical strategies that together can make a large difference in students' understanding and acceptance of evolution are extensive use of interactive engagement, a focus on critical thinking in science (especially on comparisons and explicit criteria) and using both of these in helping the students actively compare their initial conceptions (and publicly popular misconceptions) with more fully scientific conceptions. The conclusion that students' misconceptions must be dealt with systematically can be difficult for faculty who are teaching evolution since much of the students' resistance is framed in religious terms and one might be reluctant to address religious ideas in class. Applications to teaching evolution are illustrated with examples that address criteria and critical thinking, standard geology versus flood geology, evolutionary developmental biology versus organs of extreme perfection, and the importance of using humans as a central example. It is also helpful to bridge the false dichotomy, seen by many students, between atheistic evolution versus religious creationism. These applications are developed in detail and are intended to be sufficient to allow others to use these approaches in their teaching. Students and other faculty were quite supportive of these approaches as implemented in my classes.

  7. New prospects in direct, inverse and control problems for evolution equations

    CERN Document Server

    Fragnelli, Genni; Mininni, Rosa

    2014-01-01

    This book, based on a selection of talks given at a dedicated meeting in Cortona, Italy, in June 2013, shows the high degree of interaction between a number of fields related to applied sciences. Applied sciences consider situations in which the evolution of a given system over time is observed, and the related models can be formulated in terms of evolution equations (EEs). These equations have been studied intensively in theoretical research and are the source of an enormous number of applications. In this volume, particular attention is given to direct, inverse and control problems for EEs. The book provides an updated overview of the field, revealing its richness and vitality.

  8. [Relationship between self-directed learning with learning styles and strategies in medical students].

    Science.gov (United States)

    Márquez U, Carolina; Fasce H, Eduardo; Pérez V, Cristhian; Ortega B, Javiera; Parra P, Paula; Ortiz M, Liliana; Matus B, Olga; Ibáñez G, Pilar

    2014-11-01

    Self-directed learning (SDL) skills are particularly important in medical education, considering that physicians should be able to regulate their own learning experiences. To evaluate the relationship between learning styles and strategies and self-directed learning in medical students. One hundred ninety nine first year medical students (120 males) participated in the study. Preparation for Independent Learning (EPAI) scale was used to assess self-direction. Schmeck learning strategies scale and Honey and Alonso (CHAEA) scales were used to evaluate learning styles and strategies. Theoretical learning style and deep processing learning strategy had positive correlations with self-direct learning. Medical students with theoretical styles and low retention of facts are those with greater ability to self-direct their learning. Further studies are required to determine the relationship between learning styles and strategies with SDL in medical students. The acquired knowledge will allow the adjustment of teaching strategies to encourage SDL.

  9. Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes

    Directory of Open Access Journals (Sweden)

    Takehiro Nishikawa

    2012-01-01

    Full Text Available Directed evolution of proteins is a technique used to modify protein functions through “Darwinian selection.” In vitro compartmentalization (IVC is an in vitro gene screening system for directed evolution of proteins. IVC establishes the link between genetic information (genotype and the protein translated from the information (phenotype, which is essential for all directed evolution methods, by encapsulating both in a nonliving microcompartment. Herein, we introduce a new liposome-based IVC system consisting of a liposome, the protein synthesis using recombinant elements (PURE system and a fluorescence-activated cell sorter (FACS used as a microcompartment, in vitro protein synthesis system, and high-throughput screen, respectively. Liposome-based IVC is characterized by in vitro protein synthesis from a single copy of a gene in a cell-sized unilamellar liposome and quantitative functional evaluation of the synthesized proteins. Examples of liposome-based IVC for screening proteins such as GFP and β-glucuronidase are described. We discuss the future directions for this method and its applications.

  10. Progress in strategies for sequence diversity library creation for ...

    African Journals Online (AJOL)

    As the simplest technique of protein engineering, directed evolution has been ... An experiment of directed evolution comprises mutant libraries creation and ... evolution, sequence diversity creation, novel strategy, computational design, ...

  11. Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication.

    Science.gov (United States)

    Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark

    2017-09-01

    Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.

  12. Ultra-high-throughput screening method for the directed evolution of glucose oxidase.

    Science.gov (United States)

    Ostafe, Raluca; Prodanovic, Radivoje; Nazor, Jovana; Fischer, Rainer

    2014-03-20

    Glucose oxidase (GOx) is used in many industrial processes that could benefit from improved versions of the enzyme. Some improvements like higher activity under physiological conditions and thermal stability could be useful for GOx applications in biosensors and biofuel cells. Directed evolution is one of the currently available methods to engineer improved GOx variants. Here, we describe an ultra-high-throughput screening system for sorting the best enzyme variants generated by directed evolution that incorporates several methodological refinements: flow cytometry, in vitro compartmentalization, yeast surface display, fluorescent labeling of the expressed enzyme, delivery of glucose substrate to the reaction mixture through the oil phase, and covalent labeling of the cells with fluorescein-tyramide. The method enables quantitative screening of gene libraries to identify clones with improved activity and it also allows cells to be selected based not only on the overall activity but also on the specific activity of the enzyme. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. eCodonOpt: a systematic computational framework for optimizing codon usage in directed evolution experiments

    OpenAIRE

    Moore, Gregory L.; Maranas, Costas D.

    2002-01-01

    We present a systematic computational framework, eCodonOpt, for designing parental DNA sequences for directed evolution experiments through codon usage optimization. Given a set of homologous parental proteins to be recombined at the DNA level, the optimal DNA sequences encoding these proteins are sought for a given diversity objective. We find that the free energy of annealing between the recombining DNA sequences is a much better descriptor of the extent of crossover formation than sequence...

  14. Recent observations of distant matter - Direct clues to birth and evolution

    International Nuclear Information System (INIS)

    Koo, D.C.

    1988-01-01

    Highlights of recent deep observations of field galaxies, clusters of galaxies, radio galaxies, quasar absorption lines, and quasars are used to illustrate our progress since the 1981 Vatican Conference on Astrophysical Cosmology and to review the current status of evidence for evolution in their intrinsic properties and large-scale clustering. The birth and ages of galaxies can be explored directly by exploiting these classes of objects to search for primeval galaxies. 96 refs

  15. Message strategies in direct-to-consumer pharmaceutical advertising: a content analysis using Taylor's six-segment message strategy wheel.

    Science.gov (United States)

    Tsai, Wan-Hsiu Sunny; Lancaster, Alyse R

    2012-01-01

    This exploratory study applies Taylor's (1999) six-segment message strategy wheel to direct-to-consumer (DTC) pharmaceutical television commercials to understand message strategies adopted by pharmaceutical advertisers to persuade consumers. A convenience sample of 96 DTC commercial campaigns was analyzed. The results suggest that most DTC drug ads used a combination approach, providing consumers with medical and drug information while simultaneously appealing to the viewer's ego-related needs and desires. In contrast to ration and ego strategies, other approaches including routine, acute need, and social are relatively uncommon while sensory was the least common message strategy. Findings thus recognized the educational value of DTC commercials.

  16. THE STRATEGY OF DIRECT INFLATION TARGETING – EPERIENCES OF THE COUNTRIES OF MIDDLE-EAST EUROPE

    OpenAIRE

    Dorota Zbierzchowska

    2009-01-01

    This paper aims at presenting theoretical assumptions of the strategy of direct inflation targeting as well as profits and potential threats stemming from the acceptance of that strategy. Empirical analysis compares the results of implementation of the BCI strategy in the Central and Eastern European countries (Poland, Czech Republic, Romania, Slovakia, Hungary).

  17. Creation of a cardiotropic adeno-associated virus: the story of viral directed evolution

    Directory of Open Access Journals (Sweden)

    Yang Lin

    2013-02-01

    Full Text Available Abstract Adeno-associated virus (AAV is an important vector system for human gene therapy. Although use of AAV serotypes can result in efficient myocardial gene transfer, improvements in the transduction efficiency and specificity are still required. As a method for artificial modification and selection of gene function, directed evolution has been used for diverse applications in genetic engineering of enzymes and proteins. Since 2000, pioneering work has been performed on directed evolution of viral vectors. We further attempted to evolve the AAV using DNA shuffling and in vivo biopanning in a mouse model. An AAVM41 mutant was characterized, which was found to have improved transduction efficiency and specificity in myocardium, an attribute unknown for any natural AAV serotypes. This review focuses on the development of AAV vector for cardiac gene transfer, the history of directed evolution of viral vectors, and our creation of a cardiotropic AAV, which might have implications for the future design and application of viral vectors.

  18. Rapid directed evolution of stabilized proteins with cellular high-throughput encapsulation solubilization and screening (CHESS).

    Science.gov (United States)

    Yong, K J; Scott, D J

    2015-03-01

    Directed evolution is a powerful method for engineering proteins towards user-defined goals and has been used to generate novel proteins for industrial processes, biological research and drug discovery. Typical directed evolution techniques include cellular display, phage display, ribosome display and water-in-oil compartmentalization, all of which physically link individual members of diverse gene libraries to their translated proteins. This allows the screening or selection for a desired protein function and subsequent isolation of the encoding gene from diverse populations. For biotechnological and industrial applications there is a need to engineer proteins that are functional under conditions that are not compatible with these techniques, such as high temperatures and harsh detergents. Cellular High-throughput Encapsulation Solubilization and Screening (CHESS), is a directed evolution method originally developed to engineer detergent-stable G proteins-coupled receptors (GPCRs) for structural biology. With CHESS, library-transformed bacterial cells are encapsulated in detergent-resistant polymers to form capsules, which serve to contain mutant genes and their encoded proteins upon detergent mediated solubilization of cell membranes. Populations of capsules can be screened like single cells to enable rapid isolation of genes encoding detergent-stable protein mutants. To demonstrate the general applicability of CHESS to other proteins, we have characterized the stability and permeability of CHESS microcapsules and employed CHESS to generate thermostable, sodium dodecyl sulfate (SDS) resistant green fluorescent protein (GFP) mutants, the first soluble proteins to be engineered using CHESS. © 2014 Wiley Periodicals, Inc.

  19. Directed evolution of an endoinulinase from Talaromyces purpureogenus toward efficient production of inulooligosaccharides.

    Science.gov (United States)

    Afriat-Jurnou, Livnat; Cohen, Rami; Paluy, Irina; Ben-Adiva, Ran; Yadid, Itamar

    2018-02-01

    Inulinases are fructofuranosyl hydrolases that target the β-2,1 linkage of inulin and hydrolyze it into fructose, glucose and inulooligosaccharides (IOS), the latter are of growing interest as dietary fibers. Inulinases from various microorganisms have been purified, characterized and produced for industrial applications. However, there remains a need for inulinases with increased catalytic activity and better production yields to improve the hydrolysis process and fulfill the growing industrial demands for specific fibers. In this study, we used directed enzyme evolution to increase the yield and activity of an endoinulinase enzyme originated from the filamentous fungus Talaromyces purpureogenus (Penicillium purpureogenum ATCC4713). Our directed evolution approach yielded variants showing up to fivefold improvements in soluble enzyme production compared to the starting point which enabled high-yield production of highly purified recombinant enzyme. The distribution of the enzymatic reaction products demonstrated that after 24 h of incubation, the main product (57%) had a degree of polymerization of 3 (DP3). To the best of our knowledge, this is the first application of directed enzyme evolution to improve inulooligosaccharide production. The approach enabled the screening of large genetic libraries within short time frames and facilitated screening for improved enzymatic activities and properties, such as substrate specificity, product range, thermostability and pH optimum. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  20. Microstructural Evolution in Intensively Melt Sheared Direct Chill Cast Al-Alloys

    Science.gov (United States)

    Jones, S.; Rao, A. K. Prasada; Patel, J. B.; Scamans, G. M.; Fan, Z.

    The work presented here introduces the novel melt conditioned direct chill casting (MC-DC) technology, where intensive melt shearing is applied to the conventional direct-chill casting process. MC-DC casting can successfully produce high quality Al-alloy billets. The results obtained from 80 mm diameter billets cast at speed of 200 mm/min show that MC-DC casting of Al-alloys, substantially refines the microstructure and reduces macro-segregation. In this paper, we present the preliminary results and discuss microstructural evolution during MC-DC casting of Al-alloys.

  1. Application of evolution strategy algorithm for optimization of a single-layer sound absorber

    Directory of Open Access Journals (Sweden)

    Morteza Gholamipoor

    2014-12-01

    Full Text Available Depending on different design parameters and limitations, optimization of sound absorbers has always been a challenge in the field of acoustic engineering. Various methods of optimization have evolved in the past decades with innovative method of evolution strategy gaining more attention in the recent years. Based on their simplicity and straightforward mathematical representations, single-layer absorbers have been widely used in both engineering and industrial applications and an optimized design for these absorbers has become vital. In the present study, the method of evolution strategy algorithm is used for optimization of a single-layer absorber at both a particular frequency and an arbitrary frequency band. Results of the optimization have been compared against different methods of genetic algorithm and penalty functions which are proved to be favorable in both effectiveness and accuracy. Finally, a single-layer absorber is optimized in a desired range of frequencies that is the main goal of an industrial and engineering optimization process.

  2. APPLICATION OF RESTART COVARIANCE MATRIX ADAPTATION EVOLUTION STRATEGY (RCMA-ES TO GENERATION EXPANSION PLANNING PROBLEM

    Directory of Open Access Journals (Sweden)

    K. Karthikeyan

    2012-10-01

    Full Text Available This paper describes the application of an evolutionary algorithm, Restart Covariance Matrix Adaptation Evolution Strategy (RCMA-ES to the Generation Expansion Planning (GEP problem. RCMA-ES is a class of continuous Evolutionary Algorithm (EA derived from the concept of self-adaptation in evolution strategies, which adapts the covariance matrix of a multivariate normal search distribution. The original GEP problem is modified by incorporating Virtual Mapping Procedure (VMP. The GEP problem of a synthetic test systems for 6-year, 14-year and 24-year planning horizons having five types of candidate units is considered. Two different constraint-handling methods are incorporated and impact of each method has been compared. In addition, comparison and validation has also made with dynamic programming method.

  3. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

    Directory of Open Access Journals (Sweden)

    Jianhua Sui

    2008-11-01

    Full Text Available Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S protein of animal and human SARS coronaviruses (SARS-CoVs during and between two zoonotic transfers (2002/03 and 2003/04 are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID "hot spot" in a light chain CDR (complementarity determining region alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural

  4. Evolution strategies and multi-objective optimization of permanent magnet motor

    DEFF Research Database (Denmark)

    Andersen, Søren Bøgh; Santos, Ilmar

    2012-01-01

    When designing a permanent magnet motor, several geometry and material parameters are to be defined. This is not an easy task, as material properties and magnetic fields are highly non-linear and the design of a motor is therefore often an iterative process. From an engineering point of view, we...... of evolution strategies, ES to effectively design and optimize parameters of permanent magnet motors. Single as well as multi-objective optimization procedures are carried out. A modified way of creating the strategy parameters for the ES algorithm is also proposed and has together with the standard ES...

  5. A Novel Application of Synthetic Biology and Directed Evolution to Engineer Phage-based Antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Meiye [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-09-01

    The emergence of multiple drug resistant bacteria poses threats to human health, agriculture and food safety. Annually over 100,000 deaths and up to $20 billion loss to the U.S. economy are attributed to multiple drug resistant bacteria. With only four new chemical antibiotics in the drug development pipeline, we are in dire need of new solutions to address the emerging threat of multiple drug resistance. We propose a paradigm-changing approach to address the multi-drug resistant bacteria problem by utilizing Synthetic Biology (SynBio) methodologies to create and evolve “designer” bacteriophages or phages – viruses that specifically infect bacteria – to infect and kill newly emerging pathogenic bacterial strains WITHOUT the need for chemical antibiotics. A major advantage of using phage to combat pathogenic bacteria is that phages can co-evolve with their bacterial host, and Sandia can be the first in the world to establish an industrial scale Synthetic Biology pipeline for phage directed evolution for safe, targeted, customizable solution to bacterial drug resistance. Since there is no existing phage directed evolution effort within or outside of Sandia, this proposal is suitable as a high-risk LDRD effort to create the first pipeline for such an endeavor. The high potential reward nature of this proposal will be the immediate impact in decontamination and restoration of surfaces and infrastructure, with longer term impact in human or animal therapeutics. The synthetic biology and screening approaches will lead to fundamental knowledge of phage/bacteria co-evolution, making Sandia a world leader in directed evolution of bacteriophages.

  6. Modeling of microstructure evolution in direct metal laser sintering: A phase field approach

    Science.gov (United States)

    Nandy, Jyotirmoy; Sarangi, Hrushikesh; Sahoo, Seshadev

    2017-02-01

    Direct Metal Laser Sintering (DMLS) is a new technology in the field of additive manufacturing, which builds metal parts in a layer by layer fashion directly from the powder bed. The process occurs within a very short time period with rapid solidification rate. Slight variations in the process parameters may cause enormous change in the final build parts. The physical and mechanical properties of the final build parts are dependent on the solidification rate which directly affects the microstructure of the material. Thus, the evolving of microstructure plays a vital role in the process parameters optimization. Nowadays, the increase in computational power allows for direct simulations of microstructures during materials processing for specific manufacturing conditions. In this study, modeling of microstructure evolution of Al-Si-10Mg powder in DMLS process was carried out by using a phase field approach. A MATLAB code was developed to solve the set of phase field equations, where simulation parameters include temperature gradient, laser scan speed and laser power. The effects of temperature gradient on microstructure evolution were studied and found that with increase in temperature gradient, the dendritic tip grows at a faster rate.

  7. Reducing hospital readmission rates: current strategies and future directions.

    Science.gov (United States)

    Kripalani, Sunil; Theobald, Cecelia N; Anctil, Beth; Vasilevskis, Eduard E

    2014-01-01

    New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel.

  8. The RNA-world and co-evolution hypothesis and the origin of life: Implications, research strategies and perspectives

    Science.gov (United States)

    Lahav, Noam

    1993-01-01

    The applicability of the RNA-world and co-evolution hypothesis to the study of the very first stages of the origin of life is discussed. The discussion focuses on the basic differences between the two hypotheses and their implications, with regard to the reconstruction methodology, ribosome emergence, balance between ribozymes and protein enzymes, and their major difficultites. Additional complexities of the two hypotheses, such as membranes and the energy source of the first reactions, are not treated in the present work. A central element in the proposed experimental strategies is the study of the catalytic activites of very small peptides and RNA-like oligomers, according to existing, as well as to yet-to-be-invented scenarios of the two hypothesis under consideration. It is suggested that the novel directed molecular evolution technology, and molecular computational modeling, can be applied to this research. This strategy is assumed to be essential for the suggested goal of future studies of the origin of life, namely, the establishment of a `Primordial Darwinian entity'.

  9. Thermally induced structural evolution and performance of mesoporous block copolymer-directed alumina perovskite solar cells.

    KAUST Repository

    Tan, Kwan Wee

    2014-04-11

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x) material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance.

  10. Thermally induced structural evolution and performance of mesoporous block copolymer-directed alumina perovskite solar cells.

    KAUST Repository

    Tan, Kwan Wee; Moore, David T; Saliba, Michael; Sai, Hiroaki; Estroff, Lara A; Hanrath, Tobias; Snaith, Henry J; Wiesner, Ulrich

    2014-01-01

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x) material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance.

  11. Thermally Induced Structural Evolution and Performance of Mesoporous Block Copolymer-Directed Alumina Perovskite Solar Cells

    Science.gov (United States)

    2015-01-01

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI3–xClx) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI3–xClx material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance. PMID:24684494

  12. Direct detection of male quality can facilitate the evolution of female choosiness and indicators of good genes: Evolution across a continuum of indicator mechanisms.

    Science.gov (United States)

    Dhole, Sumit; Stern, Caitlin A; Servedio, Maria R

    2018-04-01

    The evolution of mating displays as indicators of male quality has been the subject of extensive theoretical and empirical research for over four decades. Research has also addressed the evolution of female mate choice favoring such indicators. Yet, much debate still exists about whether displays can evolve through the indirect benefits of female mate choice. Here, we use a population genetic model to investigate how the extent to which females can directly detect male quality influences the evolution of female choosiness and male displays. We use a continuum framework that incorporates indicator mechanisms that are traditionally modeled separately. Counter to intuition, we find that intermediate levels of direct detection of male quality can facilitate, rather than impede, the evolution of female choosiness and male displays in broad regions of this continuum. We examine how this evolution is driven by selective forces on genetic quality and on the display, and find that direct detection of male quality results in stronger indirect selection favoring female choosiness. Our results imply that displays maybe more likely to evolve when female choosiness has already evolved to discriminate perceptible forms of male quality. They also highlight the importance of considering general female choosiness, as well as preference, in studies of "good genes." © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  13. Evolution of learning strategies in temporally and spatially variable environments: a review of theory.

    Science.gov (United States)

    Aoki, Kenichi; Feldman, Marcus W

    2014-02-01

    The theoretical literature from 1985 to the present on the evolution of learning strategies in variable environments is reviewed, with the focus on deterministic dynamical models that are amenable to local stability analysis, and on deterministic models yielding evolutionarily stable strategies. Individual learning, unbiased and biased social learning, mixed learning, and learning schedules are considered. A rapidly changing environment or frequent migration in a spatially heterogeneous environment favors individual learning over unbiased social learning. However, results are not so straightforward in the context of learning schedules or when biases in social learning are introduced. The three major methods of modeling temporal environmental change--coevolutionary, two-timescale, and information decay--are compared and shown to sometimes yield contradictory results. The so-called Rogers' paradox is inherent in the two-timescale method as originally applied to the evolution of pure strategies, but is often eliminated when the other methods are used. Moreover, Rogers' paradox is not observed for the mixed learning strategies and learning schedules that we review. We believe that further theoretical work is necessary on learning schedules and biased social learning, based on models that are logically consistent and empirically pertinent. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Critical dynamics in the evolution of stochastic strategies for the iterated prisoner's dilemma.

    Directory of Open Access Journals (Sweden)

    Dimitris Iliopoulos

    2010-10-01

    Full Text Available The observed cooperation on the level of genes, cells, tissues, and individuals has been the object of intense study by evolutionary biologists, mainly because cooperation often flourishes in biological systems in apparent contradiction to the selfish goal of survival inherent in Darwinian evolution. In order to resolve this paradox, evolutionary game theory has focused on the Prisoner's Dilemma (PD, which incorporates the essence of this conflict. Here, we encode strategies for the iterated Prisoner's Dilemma (IPD in terms of conditional probabilities that represent the response of decision pathways given previous plays. We find that if these stochastic strategies are encoded as genes that undergo Darwinian evolution, the environmental conditions that the strategies are adapting to determine the fixed point of the evolutionary trajectory, which could be either cooperation or defection. A transition between cooperative and defective attractors occurs as a function of different parameters such as mutation rate, replacement rate, and memory, all of which affect a player's ability to predict an opponent's behavior. These results imply that in populations of players that can use previous decisions to plan future ones, cooperation depends critically on whether the players can rely on facing the same strategies that they have adapted to. Defection, on the other hand, is the optimal adaptive response in environments that change so quickly that the information gathered from previous plays cannot usefully be integrated for a response.

  15. Evolution of learning strategies in temporally and spatially variable environments: A review of theory

    Science.gov (United States)

    Aoki, Kenichi; Feldman, Marcus W.

    2013-01-01

    The theoretical literature from 1985 to the present on the evolution of learning strategies in variable environments is reviewed, with the focus on deterministic dynamical models that are amenable to local stability analysis, and on deterministic models yielding evolutionarily stable strategies. Individual learning, unbiased and biased social learning, mixed learning, and learning schedules are considered. A rapidly changing environment or frequent migration in a spatially heterogeneous environment favors individual learning over unbiased social learning. However, results are not so straightforward in the context of learning schedules or when biases in social learning are introduced. The three major methods of modeling temporal environmental change – coevolutionary, two-timescale, and information decay – are compared and shown to sometimes yield contradictory results. The so-called Rogers’ paradox is inherent in the two-timescale method as originally applied to the evolution of pure strategies, but is often eliminated when the other methods are used. Moreover, Rogers’ paradox is not observed for the mixed learning strategies and learning schedules that we review. We believe that further theoretical work is necessary on learning schedules and biased social learning, based on models that are logically consistent and empirically pertinent. PMID:24211681

  16. Strategy evolution driven by switching probabilities in structured multi-agent systems

    Science.gov (United States)

    Zhang, Jianlei; Chen, Zengqiang; Li, Zhiqi

    2017-10-01

    Evolutionary mechanism driving the commonly seen cooperation among unrelated individuals is puzzling. Related models for evolutionary games on graphs traditionally assume that players imitate their successful neighbours with higher benefits. Notably, an implicit assumption here is that players are always able to acquire the required pay-off information. To relax this restrictive assumption, a contact-based model has been proposed, where switching probabilities between strategies drive the strategy evolution. However, the explicit and quantified relation between a player's switching probability for her strategies and the number of her neighbours remains unknown. This is especially a key point in heterogeneously structured system, where players may differ in the numbers of their neighbours. Focusing on this, here we present an augmented model by introducing an attenuation coefficient and evaluate its influence on the evolution dynamics. Results show that the individual influence on others is negatively correlated with the contact numbers specified by the network topologies. Results further provide the conditions under which the coexisting strategies can be calculated analytically.

  17. Direct aperture deformation: An interfraction image guidance strategy

    International Nuclear Information System (INIS)

    Feng Yuanming; Castro-Pareja, Carlos; Shekhar, Raj; Yu, Cedric

    2006-01-01

    A new scheme, called direct aperture deformation (DAD), for online correction of interfraction geometric uncertainties under volumetric imaging guidance is presented. Using deformable image registration, the three-dimensional geometric transformation matrix can be derived that associates the planning image set and the images acquired on the day of treatment. Rather than replanning or moving the patient, we use the deformation matrix to morph the treatment apertures as a potential online correction method. A proof-of-principle study using an intensity-modulated radiation therapy plan for a prostate cancer patient was conducted. The method, procedure, and algorithm of DAD are described. The dose-volume histograms from the original plan, reoptimized plan, and rigid-body translation plan are compared with the ones from the DAD plan. The study showed the feasibility of the DAD as a general method for both target dislocation and deformation. As compared with using couch translation to move the patient, DAD is capable of correcting both target dislocation and deformations. As compared with reoptimization, online correction using the DAD scheme could be completed within a few minutes rather than tens of minutes and the speed gain would be at a very small cost of plan quality

  18. A Novel Strategy for landslide displacement and its direction monitoring

    Science.gov (United States)

    Zhu, Z.-W.; Yuan, Q.-Y.; Liu, D.-Y.; Liu, B.; Liu, J.-C.; Luo, H.

    2013-12-01

    Landslide monitoring is important in predicting the behavior of landslides, thereby ensuring environmental, life, and property safety. On the basis of our previous studies, we conducted the double shear test by using a third-generation optical fiber transducer that uses expandable polystyrene (EPS) as base material. However, the third-generation transducer has poor performance when cohesive force is present between the grout and capillary stainless steel pipe of the transducer. Thus, the fourth-generation optical fiber transducer was invented. Similar to the third-generation transducer, the fourth-generation transducer also used EPS as its base material. Single shear test was conducted on the fourth-generation transducer after being grouted with cement mortar (1:1 mix ratio). The micro-bend loss mechanism of the optical fiber was considered, and the optical time domain reflectometry instrument was used. The fact that the loss sequence of optical fibers subjected to loading is different at various locations is found. The relationship of the loading-point displacement VS. optical fiber sliding distance and optical loss were measured. Results show that the maximum initial measurement precision of the newly proposed device is 1mm, the corresponding sliding distance is 21 mm, and the dynamic range is 0-20 mm. The fourth-generation transducer can measure the movement direction of loadings, thus making this transducer applicable for landslide monitoring.

  19. The Evolution of Diapsid Reproductive Strategy with Inferences about Extinct Taxa.

    Directory of Open Access Journals (Sweden)

    Jason R Moore

    Full Text Available Diapsids show an extremely wide range of reproductive strategies. Offspring may receive no parental care, care from only one sex, care from both parents, or care under more complex regimes. Young may vary from independent, super-precocial hatchlings to altricial neonates needing much care before leaving the nest. Parents can invest heavily in a few young, or less so in a larger number. Here we examine the evolution of these traits across a composite phylogeny spanning the extant diapsids and including the limited number of extinct taxa for which reproductive strategies can be well constrained. Generalized estimating equation(GEE-based phylogenetic comparative methods demonstrate the influences of body mass, parental care strategy and hatchling maturity on clutch volume across the diapsids. The influence of polygamous reproduction is not important despite a large sample size. Applying the results of these models to the dinosaurs supports the hypothesis of paternal care (male only in derived non-avian theropods, previously suggested based on simpler analyses. These data also suggest that sauropodomorphs did not care for their young. The evolution of parental-care occurs in an almost linear series of transitions. Paternal care rarely gives rise to other care strategies. Where hatchling condition changes, diapsids show an almost unidirectional tendency of evolution towards increased altriciality. Transitions to social monogamy from the ancestral state in diapsids, where both sexes are polygamous, are common. In contrast, once evolved, polygyny and polyandry are very evolutionarily stable. Polygyny and maternal care correlate, as do polyandry and paternal care. Ancestral-character estimation (ACE of these care strategies with the character transition likelihoods estimated from the original data gives good confidence at most important nodes. These analyses suggest that the basalmost diapsids had no parental care. Crocodilians independently evolved

  20. Co-Evolution of Opinion and Strategy in Persuasion Dynamics:. AN Evolutionary Game Theoretical Approach

    Science.gov (United States)

    Ding, Fei; Liu, Yun; Li, Yong

    In this paper, a new model of opinion formation within the framework of evolutionary game theory is presented. The model simulates strategic situations when people are in opinion discussion. Heterogeneous agents adjust their behaviors to the environment during discussions, and their interacting strategies evolve together with opinions. In the proposed game, we take into account payoff discount to join a discussion, and the situation that people might drop out of an unpromising game. Analytical and emulational results show that evolution of opinion and strategy always tend to converge, with utility threshold, memory length, and decision uncertainty parameters influencing the convergence time. The model displays different dynamical regimes when we set differently the rule when people are at a loss in strategy.

  1. Evolution of strategies and competition in the international airline industry: a practical analysis using porter's competitive forces model

    OpenAIRE

    Zannoni, Niccolò

    2013-01-01

    This master thesis describes the evolution of the competition and strategies in the international airline industry. It studies the industry before and after deregulation, using the competitive forces model.

  2. Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.

    Science.gov (United States)

    Lucas, Bronwyn A; Lavi, Eitan; Shiue, Lily; Cho, Hana; Katzman, Sol; Miyoshi, Keita; Siomi, Mikiko C; Carmel, Liran; Ares, Manuel; Maquat, Lynne E

    2018-01-30

    Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20-25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.

  3. Focused directed evolution of beta-glucosidases: theoretical versus real effectiveness of a minimal working setup and simple robust screening

    Czech Academy of Sciences Publication Activity Database

    Mazura, P.; Filipi, T.; Souček, P.; Brzobohatý, Břetislav

    2011-01-01

    Roč. 346, č. 2 (2011), s. 238-242 ISSN 0008-6215 Institutional support: RVO:68081707 Keywords : Directed evolution * beta-Glucosidase * Mutagenesis Subject RIV: BO - Biophysics Impact factor: 2.332, year: 2011

  4. The Stability Analysis and New Torque Control Strategy of Direct-Driven PMSG Wind Turbines

    OpenAIRE

    Jun Liu; Feihang Zhou; Gungyi Wang

    2016-01-01

    This paper expounds on the direct-driven PMSG wind power system control strategy, and analyses the stability conditions of the system. The direct-driven PMSG wind power system may generate the intense mechanical vibration, when wind speed changes dramatically. This paper proposes a new type of torque control strategy, which increases the system damping effectively, mitigates mechanical vibration of the system, and enhances the stability conditions of the system. The simulation results verify ...

  5. Effects of direct instruction and strategy modeling on upper-primary students' writing development

    NARCIS (Netherlands)

    López, P.; Torrance, M.; Rijlaarsdam, G.; Fidalgo, R.

    Strategy-focused instruction is one of the most effective approaches to improve writing skills. It aims to teach developing writers strategies that give them executive control over their writing processes. Programs under this kind of instruction tend to have multiple components that include direct

  6. Outward Foreign Direct Investment from Emerging Economies and National Development Strategies

    DEFF Research Database (Denmark)

    Gammeltoft, Peter; Kokko, Ari

    2013-01-01

    Foreign direct investment (FDI) is an integral part of national development strategy throughout the developing world. However, while traditionally strategies have focused on the role of inward flows only, today, outward FDI is used on a larger scale and more deliberately to access markets...

  7. Communication Strategies in Direct-to-Consumer Prescription Drug Advertising (DTCA): Application of the Six Segment Message Strategy Wheel.

    Science.gov (United States)

    Ju, Ilwoo; Park, Jin Seong

    2015-01-01

    This study addresses a void in the literature on direct-to-consumer prescription drug advertising (DTCA) with a theory-based content analysis. The findings indicate that Taylor's communication strategy wheel provides insight into what and how pharmaceutical marketers communicate with consumers by means of DTCA. Major findings are summarized as follows: (a) In most DTC ads, informational and transformational message themes and creative approaches were simultaneously used, indicating a combination strategy; (b) DTCA message themes were associated with creative strategies in alignment with Taylor's framework; and (c) message themes and creative strategies varied across therapeutic categories and DTCA categories with different levels of ad spending. Theoretical and practical implications of the findings are discussed.

  8. No evidence for directional evolution of body mass in herbivorous theropod dinosaurs

    Science.gov (United States)

    Zanno, Lindsay E.; Makovicky, Peter J.

    2013-01-01

    The correlation between large body size and digestive efficiency has been hypothesized to have driven trends of increasing mass in herbivorous clades by means of directional selection. Yet, to date, few studies have investigated this relationship from a phylogenetic perspective, and none, to our knowledge, with regard to trophic shifts. Here, we reconstruct body mass in the three major subclades of non-avian theropod dinosaurs whose ecomorphology is correlated with extrinsic evidence of at least facultative herbivory in the fossil record—all of which also achieve relative gigantism (more than 3000 kg). Ordinary least-squares regressions on natural log-transformed mean mass recover significant correlations between increasing mass and geological time. However, tests for directional evolution in body mass find no support for a phylogenetic trend, instead favouring passive models of trait evolution. Cross-correlation of sympatric taxa from five localities in Asia reveals that environmental influences such as differential habitat sampling and/or taphonomic filtering affect the preserved record of dinosaurian body mass in the Cretaceous. Our results are congruent with studies documenting that behavioural and/or ecological factors may mitigate the benefit of increasing mass in extant taxa, and suggest that the hypothesis can be extrapolated to herbivorous lineages across geological time scales. PMID:23193135

  9. Directed Evolution to Engineer Monobody for FRET Biosensor Assembly and Imaging at Live-Cell Surface.

    Science.gov (United States)

    Limsakul, Praopim; Peng, Qin; Wu, Yiqian; Allen, Molly E; Liang, Jing; Remacle, Albert G; Lopez, Tyler; Ge, Xin; Kay, Brian K; Zhao, Huimin; Strongin, Alex Y; Yang, Xiang-Lei; Lu, Shaoying; Wang, Yingxiao

    2018-04-19

    Monitoring enzymatic activities at the cell surface is challenging due to the poor efficiency of transport and membrane integration of fluorescence resonance energy transfer (FRET)-based biosensors. Therefore, we developed a hybrid biosensor with separate donor and acceptor that assemble in situ. The directed evolution and sequence-function analysis technologies were integrated to engineer a monobody variant (PEbody) that binds to R-phycoerythrin (R-PE) dye. PEbody was used for visualizing the dynamic formation/separation of intercellular junctions. We further fused PEbody with the enhanced CFP and an enzyme-specific peptide at the extracellular surface to create a hybrid FRET biosensor upon R-PE capture for monitoring membrane-type-1 matrix metalloproteinase (MT1-MMP) activities. This biosensor revealed asymmetric distribution of MT1-MMP activities, which were high and low at loose and stable cell-cell contacts, respectively. Therefore, directed evolution and rational design are promising tools to engineer molecular binders and hybrid FRET biosensors for monitoring molecular regulations at the surface of living cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    Science.gov (United States)

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

  11. Imitative and Direct Learning as Interacting Factors in Life History Evolution.

    Science.gov (United States)

    Bullinaria, John A

    2017-01-01

    The idea that lifetime learning can have a significant effect on life history evolution has recently been explored using a series of artificial life simulations. These involved populations of competing individuals evolving by natural selection to learn to perform well on simplified abstract tasks, with the learning consisting of identifying regularities in their environment. In reality, there is more to learning than that type of direct individual experience, because it often includes a substantial degree of social learning that involves various forms of imitation of what other individuals have learned before them. This article rectifies that omission by incorporating memes and imitative learning into revised versions of the previous approach. To do this reliably requires formulating and testing a general framework for meme-based simulations that will enable more complete investigations of learning as a factor in any life history evolution scenarios. It does that by simulating imitative information transfer in terms of memes being passed between individuals, and developing a process for merging that information with the (possibly inconsistent) information acquired by direct experience, leading to a consistent overall body of learning. The proposed framework is tested on a range of learning variations and a representative set of life history factors to confirm the robustness of the approach. The simulations presented illustrate the types of interactions and tradeoffs that can emerge, and indicate the kinds of species-specific models that could be developed with this approach in the future.

  12. Evolution of learned strategy choice in a frequency-dependent game.

    Science.gov (United States)

    Katsnelson, Edith; Motro, Uzi; Feldman, Marcus W; Lotem, Arnon

    2012-03-22

    In frequency-dependent games, strategy choice may be innate or learned. While experimental evidence in the producer-scrounger game suggests that learned strategy choice may be common, a recent theoretical analysis demonstrated that learning by only some individuals prevents learning from evolving in others. Here, however, we model learning explicitly, and demonstrate that learning can easily evolve in the whole population. We used an agent-based evolutionary simulation of the producer-scrounger game to test the success of two general learning rules for strategy choice. We found that learning was eventually acquired by all individuals under a sufficient degree of environmental fluctuation, and when players were phenotypically asymmetric. In the absence of sufficient environmental change or phenotypic asymmetries, the correct target for learning seems to be confounded by game dynamics, and innate strategy choice is likely to be fixed in the population. The results demonstrate that under biologically plausible conditions, learning can easily evolve in the whole population and that phenotypic asymmetry is important for the evolution of learned strategy choice, especially in a stable or mildly changing environment.

  13. Implementation of Evolution Strategies (ES Algorithm to Optimization Lovebird Feed Composition

    Directory of Open Access Journals (Sweden)

    Agung Mustika Rizki

    2017-05-01

    Full Text Available Lovebird current society, especially popular among bird lovers. Some people began to try to develop the cultivation of these birds. In the cultivation process to consider the composition of feed to produce a quality bird. Determining the feed is not easy because it must consider the cost and need for vitamin Lovebird. This problem can be solved by the algorithm Evolution Strategies (ES. Based on test results obtained optimal fitness value of 0.3125 using a population size of 100 and optimal fitness value of 0.3267 in the generation of 1400. 

  14. Academic Self-Concept and Learning Strategies: Direction of Effect on Student Academic Achievement

    Science.gov (United States)

    McInerney, Dennis M.; Cheng, Rebecca Wing-yi; Mok, Magdalena Mo Ching; Lam, Amy Kwok Hap

    2012-01-01

    This study examined the prediction of academic self-concept (English and Mathematics) and learning strategies (deep and surface), and their direction of effect, on academic achievement (English and Mathematics) of 8,354 students from 16 secondary schools in Hong Kong. Two competing models were tested to ascertain the direction of effect: Model A…

  15. Laboratory Evolution to Alternating Substrate Environments Yields Distinct Phenotypic and Genetic Adaptive Strategies

    DEFF Research Database (Denmark)

    Sandberg, Troy E.; Lloyd, Colton J.; Palsson, Bernhard O.

    2017-01-01

    conditions and different adaptation strategies depending on the substrates being switched between; in some environments, a persistent "generalist" strain developed, while in another, two "specialist" subpopulations arose that alternated dominance. Diauxic lag phenotype varied across the generalists...... maintain simple, static culturing environments so as to reduce selection pressure complexity. In this study, we investigated the adaptive strategies underlying evolution to fluctuating environments by evolving Escherichia coli to conditions of frequently switching growth substrate. Characterization...... of evolved strains via a number of different data types revealed the various genetic and phenotypic changes implemented in pursuit of growth optimality and how these differed across the different growth substrates and switching protocols. This work not only helps to establish general principles of adaptation...

  16. Effect of migration based on strategy and cost on the evolution of cooperation

    International Nuclear Information System (INIS)

    Li, Yan; Ye, Hang

    2015-01-01

    Highlights: •Propose a migration based on strategy and cost in the Prisoner’s Dilemma Game. •The level of cooperation without mutation is higher than that with mutation. •Increased costs have no effect on the level of cooperation without mutation. •The level of cooperation decreases with the increase in cost with mutation. •An optimal density value ρ resulting in the maximum level of cooperation exists. -- Abstract: Humans consider not only their own ability but also the environment around them during the process of migration. Based on this fact, we introduce migration based on strategy and cost into the Spatial Prisoner’s Dilemma Game on a two-dimensional grid. The migration means that agents cannot move when all of the neighbors are cooperators; otherwise, agents move with a probability related to payoff and cost. The result obtained by the computer simulation shows that the moving mechanism based on strategy and cost improves the level of cooperation in a wide parameter space. This occurs because movement based on strategy effectively keeps the cooperative clusters and because movement based on cost effectively regulates the rate of movement. Both types of movement provide a favorable guarantee for the evolution of stable cooperation under the mutation rate q = 0.0. In addition, we discuss the effectiveness of the migration mechanism in the evolution of cooperation under the mutation rate q = 0.001. The result indicates that a higher level of cooperation is obtained at a lower migration cost, whereas cooperation is suppressed at a higher migration cost. Our work may provide an effective method for understanding the emergence of cooperation in our society

  17. Improving Glyphosate Oxidation Activity of Glycine Oxidase from Bacillus cereus by Directed Evolution

    Science.gov (United States)

    Zhan, Tao; Zhang, Kai; Chen, Yangyan; Lin, Yongjun; Wu, Gaobing; Zhang, Lili; Yao, Pei; Shao, Zongze; Liu, Ziduo

    2013-01-01

    Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO) has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate. Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO), we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution. Six mutants exhibiting enhanced activity toward glyphosate were screened from two rounds of error-prone PCR combined with site directed mutagenesis, and the beneficial mutations of the six evolved variants were recombined by DNA shuffling. Four recombinants were generated and, when compared with the wild-type BceGO, the most active mutant B3S1 showed the highest activity, exhibiting a 160-fold increase in substrate affinity, a 326-fold enhancement in catalytic efficiency against glyphosate, with little difference between their pH and temperature stabilities. The role of these mutations was explored through structure modeling and molecular docking, revealing that the Arg51 mutation is near the active site and could be an important residue contributing to the stabilization of glyphosate binding, while the role of the remaining mutations is unclear. These results provide insight into the application of directed evolution in optimizing glycine oxidase function and have laid a foundation for the development of glyphosate-tolerant crops. PMID:24223901

  18. Improving glyphosate oxidation activity of glycine oxidase from Bacillus cereus by directed evolution.

    Directory of Open Access Journals (Sweden)

    Tao Zhan

    Full Text Available Glyphosate, a broad spectrum herbicide widely used in agriculture all over the world, inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, and glycine oxidase (GO has been reported to be able to catalyze the oxidative deamination of various amines and cleave the C-N bond in glyphosate. Here, in an effort to improve the catalytic activity of the glycine oxidase that was cloned from a glyphosate-degrading marine strain of Bacillus cereus (BceGO, we used a bacteriophage T7 lysis-based method for high-throughput screening of oxidase activity and engineered the gene encoding BceGO by directed evolution. Six mutants exhibiting enhanced activity toward glyphosate were screened from two rounds of error-prone PCR combined with site directed mutagenesis, and the beneficial mutations of the six evolved variants were recombined by DNA shuffling. Four recombinants were generated and, when compared with the wild-type BceGO, the most active mutant B3S1 showed the highest activity, exhibiting a 160-fold increase in substrate affinity, a 326-fold enhancement in catalytic efficiency against glyphosate, with little difference between their pH and temperature stabilities. The role of these mutations was explored through structure modeling and molecular docking, revealing that the Arg(51 mutation is near the active site and could be an important residue contributing to the stabilization of glyphosate binding, while the role of the remaining mutations is unclear. These results provide insight into the application of directed evolution in optimizing glycine oxidase function and have laid a foundation for the development of glyphosate-tolerant crops.

  19. [The evolution of nursing shortage and strategies to face it: a longitudinal study in 11 hospitals].

    Science.gov (United States)

    Stringhetta, Francesca; Dal Ponte, Adriana; Palese, Alvisa

    2012-01-01

    To describe the perception of the evolution of nursing shortage from 2000 to 2009 according to Nursing Coordinators and the strategies to face it. Nursing coordinators of 11 hospitals or districts of Friuli Venezia Giulia, Trentino Alto Adige and Veneto regions were interviewed in 2000, 2004 and 2009 to collect data and assess their perception on nurses' shortage. In the first interview the medium gap between staff planned and in service was -5.4%; in 2004 -9.4% and in 2009 -3.3%. The shortage, once with a seasonal trend is now constant and appreciated in all the wards. In years 2000 and 2004 on average 5 strategies to face the shortage were implemented, in 2009 7. No systematic strategies have been used with the exception of the unification of wards, mainly during summer for letting people go on holydays. According to Nursing Coordinators the effects of the shortage are already observable (although not quantified) on patients and nurses. The nurses' shortage has been one of the challenges of the last 10 years. Its causes have changed but not the strategies implemented.

  20. Evolution of the heteroharmonic strategy for target-range computation in the echolocation of Mormoopidae.

    Directory of Open Access Journals (Sweden)

    Emanuel C Mora

    2013-06-01

    Full Text Available Echolocating bats use the time elapsed from biosonar pulse emission to the arrival of echo (defined as echo-delay to assess target-distance. Target-distance is represented in the brain by delay-tuned neurons that are classified as either heteroharmonic or homoharmormic. Heteroharmonic neurons respond more strongly to pulse-echo pairs in which the timing of the pulse is given by the fundamental biosonar harmonic while the timing of echoes is provided by one (or several of the higher order harmonics. On the other hand, homoharmonic neurons are tuned to the echo delay between similar harmonics in the emitted pulse and echo. It is generally accepted that heteroharmonic computations are advantageous over homoharmonic computations; i.e. heteroharmonic neurons receive information from call and echo in different frequency-bands which helps to avoid jamming between pulse and echo signals. Heteroharmonic neurons have been found in two species of the family Mormoopidae (Pteronotus parnellii and Pteronotus quadridens and in Rhinolophus rouxi. Recently, it was proposed that heteroharmonic target-range computations are a primitive feature of the genus Pteronotus that was preserved in the evolution of the genus. Here we review recent findings on the evolution of echolocation in Mormoopidae, and try to link those findings to the evolution of the heteroharmonic computation strategy. We stress the hypothesis that the ability to perform heteroharmonic computations evolved separately from the ability of using long constant-frequency echolocation calls, high duty cycle echolocation and Doppler Shift Compensation. Also, we present the idea that heteroharmonic computations might have been of advantage for categorizing prey size, hunting eared insects and living in large conspecific colonies. We make five testable predictions that might help future investigations to clarify the evolution of the heteroharmonic echolocation in Mormoopidae and other families.

  1. The use of benthic indicators in Europe: from the Water Framework Directive to the Marine Strategy Framework Directive.

    Science.gov (United States)

    Van Hoey, Gert; Borja, Angel; Birchenough, Silvana; Buhl-Mortensen, Lene; Degraer, Steven; Fleischer, Dirk; Kerckhof, Francis; Magni, Paolo; Muxika, Iñigo; Reiss, Henning; Schröder, Alexander; Zettler, Michael L

    2010-12-01

    The Water Framework Directive (WFD) and the Marine Strategy Framework Directive (MSFD) are the European umbrella regulations for water systems. It is a challenge for the scientific community to translate the principles of these directives into realistic and accurate approaches. The aim of this paper, conducted by the Benthos Ecology Working Group of ICES, is to describe how the principles have been translated, which were the challenges and best way forward. We have tackled the following principles: the ecosystem-based approach, the development of benthic indicators, the definition of 'pristine' or sustainable conditions, the detection of pressures and the development of monitoring programs. We concluded that testing and integrating the different approaches was facilitated during the WFD process, which led to further insights and improvements, which the MSFD can rely upon. Expert involvement in the entire implementation process proved to be of vital importance. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. LONG-TERM EVOLUTION OF DOUBLE WHITE DWARF BINARIES ACCRETING THROUGH DIRECT IMPACT

    International Nuclear Information System (INIS)

    Kremer, Kyle; Kalogera, Vassiliki; Sepinsky, Jeremy

    2015-01-01

    We calculate the long-term evolution of angular momentum in double white dwarf binaries undergoing direct impact accretion over a broad range of parameter space. We allow the rotation rate of both components to vary and account for the exchange of angular momentum between the spins of the white dwarfs and the orbit, while conserving the total angular momentum. We include gravitational, tidal, and mass transfer effects in the orbital evolution, and allow the Roche radius of the donor star to vary with both the stellar mass and the rotation rate. We examine the long-term stability of these systems, focusing in particular on those systems that may be progenitors of AM CVn or SNe Ia. We find that our analysis yields an increase in the predicted number of stable systems compared to that in previous studies. Additionally, we find that by properly accounting for the effects of asynchronism between the donor and the orbit on the Roche-lobe size, we eliminate oscillations in the orbital parameters, which were found in previous studies. Removing these oscillations can reduce the peak mass transfer rate in some systems, keeping them from entering an unstable mass transfer phase

  3. Limits to behavioral evolution: the quantitative genetics of a complex trait under directional selection.

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2013-11-01

    Replicated selection experiments provide a powerful way to study how "multiple adaptive solutions" may lead to differences in the quantitative-genetic architecture of selected traits and whether this may translate into differences in the timing at which evolutionary limits are reached. We analyze data from 31 generations (n=17,988) of selection on voluntary wheel running in house mice. The rate of initial response, timing of selection limit, and height of the plateau varied significantly between sexes and among the four selected lines. Analyses of litter size and realized selection differentials seem to rule out counterposing natural selection as a cause of the selection limits. Animal-model analyses showed that although the additive genetic variance was significantly lower in selected than control lines, both before and after the limits, the decrease was not sufficient to explain the limits. Moreover, directional selection promoted a negative covariance between additive and maternal genetic variance over the first 10 generations. These results stress the importance of replication in selection studies of higher-level traits and highlight the fact that long-term predictions of response to selection are not necessarily expected to be linear because of the variable effects of selection on additive genetic variance and maternal effects. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  4. Biocatalysts for the pharmaceutical industry created by structure-guided directed evolution of stereoselective enzymes.

    Science.gov (United States)

    Li, Guangyue; Wang, Jian-Bo; Reetz, Manfred T

    2018-04-01

    Enzymes have been used for a long time as catalysts in the asymmetric synthesis of chiral intermediates needed in the production of therapeutic drugs. However, this alternative to man-made catalysts has suffered traditionally from distinct limitations, namely the often observed wrong or insufficient enantio- and/or regioselectivity, low activity, narrow substrate range, and insufficient thermostability. With the advent of directed evolution, these problems can be generally solved. The challenge is to develop and apply the most efficient mutagenesis methods which lead to highest-quality mutant libraries requiring minimal screening. Structure-guided saturation mutagenesis and its iterative form have emerged as the method of choice for evolving stereo- and regioselective mutant enzymes needed in the asymmetric synthesis of chiral intermediates. The number of (industrial) applications in the preparation of chiral pharmaceuticals is rapidly increasing. This review features and analyzes typical case studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Studying fatigue damage evolution in uni-directional composites using x-ray computed tomography

    DEFF Research Database (Denmark)

    Mikkelsen, Lars Pilgaard

    , it will be possible to lower the costs of energy for wind energy based electricity. In the present work, a lab-source x-ray computed tomography equipment (Zeiss Xradia 520 Versa) has been used in connection with ex-situ fatigue testing of uni-directional composites in order to identify fibre failure during...... comparable x-ray studies) have been used in order to ensure a representative test volume during the ex-situ fatigue testing. Using the ability of the x-ray computed tomography to zoom into regions of interest, non-destructive, the fatigue damage evolution in a repeating ex-situ fatigue loaded test sample has...... improving the fatigue resistance of non-crimp fabric used in the wind turbine industry can be made....

  6. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution.

    Science.gov (United States)

    Renata, Hans; Wang, Z Jane; Arnold, Frances H

    2015-03-09

    High selectivity and exquisite control over the outcome of reactions entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature's known repertoire. In this Review, we outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progression has been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been exploited for chemical synthesis, with an emphasis on reactions that do not have natural counterparts. Non-natural activities can be improved by directed evolution, thus mimicking the process used by nature to create new catalysts. Finally, we describe the discovery of non-native catalytic functions that may provide future opportunities for the expansion of the enzyme universe. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. SNAP dendrimers: multivalent protein display on dendrimer-like DNA for directed evolution.

    Science.gov (United States)

    Kaltenbach, Miriam; Stein, Viktor; Hollfelder, Florian

    2011-09-19

    Display systems connect a protein with the DNA encoding it. Such systems (e.g., phage or ribosome display) have found widespread application in the directed evolution of protein binders and constitute a key element of the biotechnological toolkit. In this proof-of-concept study we describe the construction of a system that allows the display of multiple copies of a protein of interest in order to take advantage of avidity effects during affinity panning. To this end, dendrimer-like DNA is used as a scaffold with docking points that can join the coding DNA with multiple protein copies. Each DNA construct is compartmentalised in water-in-oil emulsion droplets. The corresponding protein is expressed, in vitro, inside the droplets as a SNAP-tag fusion. The covalent bond between DNA and the SNAP-tag is created by reaction with dendrimer-bound benzylguanine (BG). The ability to form dendrimer-like DNA straightforwardly from oligonucleotides bearing BG allowed the comparison of a series of templates differing in size, valency and position of BG. In model selections the most efficient constructs show recoveries of up to 0.86 % and up to 400-fold enrichments. The comparison of mono- and multivalent constructs suggests that the avidity effect enhances enrichment by up to fivefold and recovery by up to 25-fold. Our data establish a multivalent format for SNAP-display based on dendrimer-like DNA as the first in vitro display system with defined tailor-made valencies and explore a new application for DNA nanostructures. These data suggest that multivalent SNAP dendrimers have the potential to facilitate the selection of protein binders especially during early rounds of directed evolution, allowing a larger diversity of candidate binders to be recovered. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. TRADE AND FOREIGN DIRECT INVESTMENT MANAGEMENT STRATEGIES FOR U.S. PROCESSED FOOD FIRMS IN CHINA

    OpenAIRE

    Marchant, Mary A.; Saghaian, Sayed H.; Vickner, Steven S.

    1999-01-01

    This research examines the relationship between U.S. foreign direct investment (FDI) and exports of processed foods to China and identifies management strategies to enhance U.S. competitiveness. Two-stage least-squares empirical econometric results from a simultaneous equation system indicate that there exists a strong complementary relationship between U.S exports and FDI into China. Therefore, the appropriate managerial strategy to access Chinese processed foods markets is to increase overa...

  10. Nurses' use of pliable and directed strategies when encountering children in child and school healthcare.

    Science.gov (United States)

    Harder, Maria; Enskär, Karin; Golsäter, Marie

    2017-03-01

    Nurses in Swedish child and school healthcare need to balance their assignment of promoting children's health and development based on the national health-monitoring programme with their responsibility to consider each child's needs. In this balancing act, they encounter children through directed and pliable strategies to fulfil their professional obligations. The aim of this study was to analyse the extent to which nurses use different strategies when encountering children during their recurrent health visits throughout childhood. A quantitative descriptive content analysis was used to code 30 video recordings displaying nurses' encounters with children (3-16 years of age). A constructed observation protocol was used to identify the codes. The results show that nurses use pliable strategies (58%) and directed strategies (42%) in encounters with children. The action they use the most within the pliable strategy is encouraging (51%), while in the directed strategy, the action they use most is instructing (56%). That they primarily use these opposing actions can be understood as trying to synthesize their twofold assignment. However, they seem to act pliably to be able to fulfil their public function as dictated by the national health-monitoring programme, rather than to meet each child's needs.

  11. The skeletal ontogeny of Astatotilapia burtoni - a direct-developing model system for the evolution and development of the teleost body plan.

    Science.gov (United States)

    Woltering, Joost M; Holzem, Michaela; Schneider, Ralf F; Nanos, Vasilios; Meyer, Axel

    2018-04-03

    The experimental approach to the evolution and development of the vertebrate skeleton has to a large extent relied on "direct-developing" amniote model organisms, such as the mouse and the chicken. These organisms can however only be partially informative where it concerns secondarily lost features or anatomical novelties not present in their lineages. The widely used anamniotes Xenopus and zebrafish are "indirect-developing" organisms that proceed through an extended time as free-living larvae, before adopting many aspects of their adult morphology, complicating experiments at these stages, and increasing the risk for lethal pleiotropic effects using genetic strategies. Here, we provide a detailed description of the development of the osteology of the African mouthbrooding cichlid Astatotilapia burtoni, primarily focusing on the trunk (spinal column, ribs and epicentrals) and the appendicular skeleton (pectoral, pelvic, dorsal, anal, caudal fins and scales), and to a lesser extent on the cranium. We show that this species has an extremely "direct" mode of development, attains an adult body plan within 2 weeks after fertilization while living off its yolk supply only, and does not pass through a prolonged larval period. As husbandry of this species is easy, generation time is short, and the species is amenable to genetic targeting strategies through microinjection, we suggest that the use of this direct-developing cichlid will provide a valuable model system for the study of the vertebrate body plan, particularly where it concerns the evolution and development of fish or teleost specific traits. Based on our results we comment on the development of the homocercal caudal fin, on shared ontogenetic patterns between pectoral and pelvic girdles, and on the evolution of fin spines as novelty in acanthomorph fishes. We discuss the differences between "direct" and "indirect" developing actinopterygians using a comparison between zebrafish and A. burtoni development.

  12. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation

    Science.gov (United States)

    Mackey, Tim K.

    2016-01-01

    The adoption and use of digital forms of direct-to-consumer advertising (also known as "eDTCA") is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA) notices of violations (NOVs) and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the "disruptive" qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored. PMID:27239871

  13. Volatility measurement with directional change in Chinese stock market: Statistical property and investment strategy

    Science.gov (United States)

    Ma, Junjun; Xiong, Xiong; He, Feng; Zhang, Wei

    2017-04-01

    The stock price fluctuation is studied in this paper with intrinsic time perspective. The event, directional change (DC) or overshoot, are considered as time scale of price time series. With this directional change law, its corresponding statistical properties and parameter estimation is tested in Chinese stock market. Furthermore, a directional change trading strategy is proposed for invest in the market portfolio in Chinese stock market, and both in-sample and out-of-sample performance are compared among the different method of model parameter estimation. We conclude that DC method can capture important fluctuations in Chinese stock market and gain profit due to the statistical property that average upturn overshoot size is bigger than average downturn directional change size. The optimal parameter of DC method is not fixed and we obtained 1.8% annual excess return with this DC-based trading strategy.

  14. Win-win strategies in directing low-carbon resilient development path

    International Nuclear Information System (INIS)

    Masui, Toshihiko; Kainuma, Mikiko

    2015-01-01

    This section explores big win-win strategies in directing low carbon resilient development path. There are lots of “leapfrog” development possibilities in developing countries, which go directly from a status of under-development through to efficient and environmentally benign lifestyle. To achieve low carbon resilient paths, not only technology development but also institutional and behavioral changes are required. Science-policy nexus is also discussed.

  15. Relationship between self-directed learning with learning styles and strategies in medical students

    OpenAIRE

    Márquez U, Carolina; Fasce H, Eduardo; Pérez V, Cristhian; Ortega B, Javiera; Parra P, Paula; Ortiz M, Liliana; Matus B, Olga; Ibáñez G, Pilar

    2014-01-01

    Background: Self-directed learning (SDL) skills are particularly important in medical education, considering that physicians should be able to regulate their own learning experiences. Aim: To evaluate the relationship between learning styles and strategies and self-directed learning in medical students. Material and Methods: One hundred ninety nine first year medical students (120 males) participated in the study. Preparation for Independent Learning (EPAI) scale was used to assess self-direc...

  16. The evolution of pattern camouflage strategies in waterfowl and game birds.

    Science.gov (United States)

    Marshall, Kate L A; Gluckman, Thanh-Lan

    2015-05-01

    Visual patterns are common in animals. A broad survey of the literature has revealed that different patterns have distinct functions. Irregular patterns (e.g., stipples) typically function in static camouflage, whereas regular patterns (e.g., stripes) have a dual function in both motion camouflage and communication. Moreover, irregular and regular patterns located on different body regions ("bimodal" patterning) can provide an effective compromise between camouflage and communication and/or enhanced concealment via both static and motion camouflage. Here, we compared the frequency of these three pattern types and traced their evolutionary history using Bayesian comparative modeling in aquatic waterfowl (Anseriformes: 118 spp.), which typically escape predators by flight, and terrestrial game birds (Galliformes: 170 spp.), which mainly use a "sit and hide" strategy to avoid predation. Given these life histories, we predicted that selection would favor regular patterning in Anseriformes and irregular or bimodal patterning in Galliformes and that pattern function complexity should increase over the course of evolution. Regular patterns were predominant in Anseriformes whereas regular and bimodal patterns were most frequent in Galliformes, suggesting that patterns with multiple functions are broadly favored by selection over patterns with a single function in static camouflage. We found that the first patterns to evolve were either regular or bimodal in Anseriformes and either irregular or regular in Galliformes. In both orders, irregular patterns could evolve into regular patterns but not the reverse. Our hypothesis of increasing complexity in pattern camouflage function was supported in Galliformes but not in Anseriformes. These results reveal a trajectory of pattern evolution linked to increasing function complexity in Galliformes although not in Anseriformes, suggesting that both ecology and function complexity can have a profound influence on pattern evolution.

  17. Application of Evolution Strategies to the Design of Tracking Filters with a Large Number of Specifications

    Directory of Open Access Journals (Sweden)

    Jesús García Herrero

    2003-07-01

    Full Text Available This paper describes the application of evolution strategies to the design of interacting multiple model (IMM tracking filters in order to fulfill a large table of performance specifications. These specifications define the desired filter performance in a thorough set of selected test scenarios, for different figures of merit and input conditions, imposing hundreds of performance goals. The design problem is stated as a numeric search in the filter parameters space to attain all specifications or at least minimize, in a compromise, the excess over some specifications as much as possible, applying global optimization techniques coming from evolutionary computation field. Besides, a new methodology is proposed to integrate specifications in a fitness function able to effectively guide the search to suitable solutions. The method has been applied to the design of an IMM tracker for a real-world civil air traffic control application: the accomplishment of specifications defined for the future European ARTAS system.

  18. Cloud computing task scheduling strategy based on differential evolution and ant colony optimization

    Science.gov (United States)

    Ge, Junwei; Cai, Yu; Fang, Yiqiu

    2018-05-01

    This paper proposes a task scheduling strategy DEACO based on the combination of Differential Evolution (DE) and Ant Colony Optimization (ACO), aiming at the single problem of optimization objective in cloud computing task scheduling, this paper combines the shortest task completion time, cost and load balancing. DEACO uses the solution of the DE to initialize the initial pheromone of ACO, reduces the time of collecting the pheromone in ACO in the early, and improves the pheromone updating rule through the load factor. The proposed algorithm is simulated on cloudsim, and compared with the min-min and ACO. The experimental results show that DEACO is more superior in terms of time, cost, and load.

  19. The evolution of competitive settlement strategies in Fijian prehistory : results of excavations and radiometric dating

    International Nuclear Information System (INIS)

    Field, J.S.

    2003-01-01

    A series of excavations were completed between June 2001 and March 2002 in the Fiji Islands. The goal of this research was to investigate the evolution of competitive settlement strategies in Fijian prehistory from an archaeological and evolutionary ecological perspective. Twelve sites were excavated and mapped in the Sigatoka Valley, located in the southwestern corner of the main island of Viti Levu. Excavations were focused on determining the chronology of fortifications in the region, and the collected samples were compared to expectations based on GIS-based analyses of land productivity and historical documents pertaining to late-period warfare. Over four hundred archaeological sites have been identified in the Sigatoka Valley, and of these roughly one-third are purely defensive in configuration, with no immediate access to water or arable land. The Waikato Archaeological Dating Fund provided four radiometric dates for three defensive sites, and one site associated with a production area. (author). 6 refs., 1 fig

  20. Convergent adaptive evolution in marginal environments: unloading transposable elements as a common strategy among mangrove genomes.

    Science.gov (United States)

    Lyu, Haomin; He, Ziwen; Wu, Chung-I; Shi, Suhua

    2018-01-01

    Several clades of mangrove trees independently invade the interface between land and sea at the margin of woody plant distribution. As phenotypic convergence among mangroves is common, the possibility of convergent adaptation in their genomes is quite intriguing. To study this molecular convergence, we sequenced multiple mangrove genomes. In this study, we focused on the evolution of transposable elements (TEs) in relation to the genome size evolution. TEs, generally considered genomic parasites, are the most common components of woody plant genomes. Analyzing the long terminal repeat-retrotransposon (LTR-RT) type of TE, we estimated their death rates by counting solo-LTRs and truncated elements. We found that all lineages of mangroves massively and convergently reduce TE loads in comparison to their nonmangrove relatives; as a consequence, genome size reduction happens independently in all six mangrove lineages; TE load reduction in mangroves can be attributed to the paucity of young elements; the rarity of young LTR-RTs is a consequence of fewer births rather than access death. In conclusion, mangrove genomes employ a convergent strategy of TE load reduction by suppressing element origination in their independent adaptation to a new environment. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  1. Mini-review: Strategies for Variation and Evolution of Bacterial Antigens

    Science.gov (United States)

    Foley, Janet

    2015-01-01

    Across the eubacteria, antigenic variation has emerged as a strategy to evade host immunity. However, phenotypic variation in some of these antigens also allows the bacteria to exploit variable host niches as well. The specific mechanisms are not shared-derived characters although there is considerable convergent evolution and numerous commonalities reflecting considerations of natural selection and biochemical restraints. Unlike in viruses, mechanisms of antigenic variation in most bacteria involve larger DNA movement such as gene conversion or DNA rearrangement, although some antigens vary due to point mutations or modified transcriptional regulation. The convergent evolution that promotes antigenic variation integrates various evolutionary forces: these include mutations underlying variant production; drift which could remove alleles especially early in infection or during life history phases in arthropod vectors (when the bacterial population size goes through a bottleneck); selection not only for any particular variant but also for the mechanism for the production of variants (i.e., selection for mutability); and overcoming negative selection against variant production. This review highlights the complexities of drivers of antigenic variation, in particular extending evaluation beyond the commonly cited theory of immune evasion. A deeper understanding of the diversity of purpose and mechanisms of antigenic variation in bacteria will contribute to greater insight into bacterial pathogenesis, ecology and coevolution with hosts. PMID:26288700

  2. Directed evolution of xylose isomerase for improved xylose catabolism and fermentation in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Lee, Sun-Mi; Jellison, Taylor; Alper, Hal S

    2012-08-01

    The heterologous expression of a highly functional xylose isomerase pathway in Saccharomyces cerevisiae would have significant advantages for ethanol yield, since the pathway bypasses cofactor requirements found in the traditionally used oxidoreductase pathways. However, nearly all reported xylose isomerase-based pathways in S. cerevisiae suffer from poor ethanol productivity, low xylose consumption rates, and poor cell growth compared with an oxidoreductase pathway and, additionally, often require adaptive strain evolution. Here, we report on the directed evolution of the Piromyces sp. xylose isomerase (encoded by xylA) for use in yeast. After three rounds of mutagenesis and growth-based screening, we isolated a variant containing six mutations (E15D, E114G, E129D, T142S, A177T, and V433I) that exhibited a 77% increase in enzymatic activity. When expressed in a minimally engineered yeast host containing a gre3 knockout and tal1 and XKS1 overexpression, the strain expressing this mutant enzyme improved its aerobic growth rate by 61-fold and both ethanol production and xylose consumption rates by nearly 8-fold. Moreover, the mutant enzyme enabled ethanol production by these yeasts under oxygen-limited fermentation conditions, unlike the wild-type enzyme. Under microaerobic conditions, the ethanol production rates of the strain expressing the mutant xylose isomerase were considerably higher than previously reported values for yeast harboring a xylose isomerase pathway and were also comparable to those of the strains harboring an oxidoreductase pathway. Consequently, this study shows the potential to evolve a xylose isomerase pathway for more efficient xylose utilization.

  3. Using biological effects tools to define Good Environmental Status under the Marine Strategy Framework Directive

    NARCIS (Netherlands)

    Lyons, B.P.; Thain, J.E.; Hylland, K.; Davis, I.; Vethaak, A.D.

    2010-01-01

    The use of biological effects tools offer enormous potential to meet the challenges outlined by the European Union Marine Strategy Framework Directive (MSFD) whereby Member States are required to develop a robust set of tools for defining 11 qualitative descriptors of Good Environmental Status

  4. The Application of Self-Directed Learning in a Marketing Strategy Capstone Course

    Science.gov (United States)

    Gray, David M.

    2011-01-01

    Capstone courses can create a space for students and educators to act as co-producers of desired learning outcomes which are directly relevant to the world of work. This study uses an auto-ethnographic case study approach to demonstrate how a mixed model learning approach evolved in a capstone marketing strategy unit in a marketing major at an…

  5. EFL Learners' Use of Direct Strategies in Competitive and Cooperative Learning Contexts

    Science.gov (United States)

    Zarei, Abbas Ali; Layeq, Hamide

    2016-01-01

    This study investigated the effects of competitive and cooperative teaching techniques on Iranian adult EFL learners' use of direct strategies. To this end, a sample of 88 non-English major university students at Sohrevardi Nonprofit College in Qazvin were assigned to two groups, and each group received instruction under one of the treatment…

  6. INTERNATIONALIZATION STRATEGIES OF THE BRAZILIAN MEAT AGRIBUSINESS SECTOR: EXPORTS OR DIRECT INVESTMENT ABROAD?

    Directory of Open Access Journals (Sweden)

    Eva Stal

    2010-11-01

    Full Text Available The article analyzes the internationalization strategies of the four largest Brazilian companies in the meat (beef, pork and poultry agribusiness sector, by considering the comparative and competitive advantages of the country and the companies. JBS, Marfrig, Sadia and Perdigão were studied, of which the last two merged in May 2009, forming Brasil Foods. The authors looked into what led these companies to start investing  abroad directly, as from 2005, as a complement to their exports, the preferred strategy for placing products in foreign markets. The research method used was the multiple case study, drawing on primary data (interviews, corporate annual reports, financial statements, press releases and shareholder information and secondary data (theses, dissertations, academic articles, reports in newspapers and business journals, using bibliographic and documentary research. Everything was analyzed in the light of international business and strategy theories. The results show that exports still predominate and that investing directly abroad was, in principle, a reactive strategy to sanitary barriers against Brazilian products. However, the acquisition of companies in restriction-free countries has increased as part of a forward-looking strategy for gaining access to new markets and strengthening brands. Key-words: Agribusiness. Internationalization. Strategy

  7. Evolved α-factor prepro-leaders for directed laccase evolution in Saccharomyces cerevisiae.

    Science.gov (United States)

    Mateljak, Ivan; Tron, Thierry; Alcalde, Miguel

    2017-11-01

    Although the functional expression of fungal laccases in Saccharomyces cerevisiae has proven to be complicated, the replacement of signal peptides appears to be a suitable approach to enhance secretion in directed evolution experiments. In this study, twelve constructs were prepared by fusing native and evolved α-factor prepro-leaders from S. cerevisiae to four different laccases with low-, medium- and high-redox potential (PM1L from basidiomycete PM1; PcL from Pycnoporus cinnabarinus; TspC30L from Trametes sp. strain C30; and MtL from Myceliophthora thermophila). Microcultures of the prepro-leader:laccase fusions were grown in selective expression medium that used galactose as both the sole carbon source and as the inducer of expression so that the secretion and activity were assessed with low- and high-redox potential mediators in a high-throughput screening context. With total activity improvements as high as sevenfold over those obtained with the native α-factor prepro-leader, the evolved prepro-leader from PcL (α PcL ) most strongly enhanced secretion of the high- and medium-redox potential laccases PcL, PM1L and TspC30L in the microtiter format with an expression pattern driven by prepro-leaders in the order α PcL  > α PM 1L  ~ α native . By contrast, the pattern of the low-redox potential MtL was α native  > α PcL  > α PM 1L . When produced in flask with rich medium, the evolved prepro-leaders outperformed the α native signal peptide irrespective of the laccase attached, enhancing secretion over 50-fold. Together, these results highlight the importance of using evolved α-factor prepro-leaders for functional expression of fungal laccases in directed evolution campaigns. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  8. Directed evolution of an LBP/CD14 inhibitory peptide and its anti-endotoxin activity.

    Directory of Open Access Journals (Sweden)

    Li Fang

    Full Text Available BACKGROUND: LPS-binding protein (LBP and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12 for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity. In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity. METHODS: We used error-prone PCR (ep-PCR and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12. RESULTS: 11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T to methionine (M mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (P<0.05. Compared to MP12, P1 significantly improved arterial oxygen pressure, an oxygenation index, and lung pathology scores in LPS-induced ARDS rats (P<0.05. CONCLUSION: By in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1 with a threonine (T-to-methionine (M mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.

  9. Host-parasite coevolution can promote the evolution of seed banking as a bet-hedging strategy.

    Science.gov (United States)

    Verin, Mélissa; Tellier, Aurélien

    2018-04-20

    Seed (egg) banking is a common bet-hedging strategy maximizing the fitness of organisms facing environmental unpredictability by the delayed emergence of offspring. Yet, this condition often requires fast and drastic stochastic shifts between good and bad years. We hypothesize that the host seed banking strategy can evolve in response to coevolution with parasites because the coevolutionary cycles promote a gradually changing environment over longer times than seed persistence. We study the evolution of host germination fraction as a quantitative trait using both pairwise competition and multiple mutant competition methods, while the germination locus can be genetically linked or unlinked with the host locus under coevolution. In a gene-for-gene model of coevolution, hosts evolve a seed bank strategy under unstable coevolutionary cycles promoted by moderate to high costs of resistance or strong disease severity. Moreover, when assuming genetic linkage between coevolving and germination loci, the resistant genotype always evolves seed banking in contrast to susceptible hosts. Under a matching-allele interaction, both hosts' genotypes exhibit the same seed banking strategy irrespective of the genetic linkage between loci. We suggest host-parasite coevolution as an additional hypothesis for the evolution of seed banking as a temporal bet-hedging strategy. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  10. PREDIKSI CHURN DAN SEGMENTASI PELANGGAN MENGGUNAKAN BACKPROPAGATION NEURAL NETWORK BERBASIS EVOLUTION STRATEGIES

    Directory of Open Access Journals (Sweden)

    Junta Zeniarja

    2015-05-01

    Full Text Available Pelanggan merupakan bagian penting dalam memastikan keunggulan dan kelangsungan hidup perusahaan. Oleh karena itu perlu untuk memiliki sistem manajemen untuk memastikan pelanggan tetap setia dan tidak pindah ke pesaing lain, yang dikenal sebagai manajemen churn. Prediksi churn pelanggan adalah bagian dari manajemen churn, yang memprediksi perilaku pelanggan dengan klasifikasi pelanggan setia dan mana yang cenderung pindah ke kompetitor lain. Keakuratan prediksi ini mutlak diperlukan karena tingginya tingkat migrasi pelanggan ke perusahaan pesaing. Hal ini penting karena biaya yang digunakan untuk meraih pelanggan baru jauh lebih tinggi dibandingkan dengan mempertahankan loyalitas pelanggan yang sudah ada. Meskipun banyak studi tentang prediksi churn pelanggan yang telah dilakukan, penelitian lebih lanjut masih diperlukan untuk meningkatkan akurasi prediksi. Penelitian ini akan membahas penggunaan teknik data mining Backpropagation Neural Network (BPNN in hybrid dengan Strategi Evolution (ES untuk atribut bobot. Validasi model dilakukan dengan menggunakan validasi Palang 10-Fold dan evaluasi pengukuran dilakukan dengan menggunakan matriks kebingungan dan Area bawah ROC Curve (AUC. Hasil percobaan menunjukkan bahwa hibrida BPNN dengan ES mencapai kinerja yang lebih baik daripada Basic BPNN. Kata kunci: data mining, churn, prediksi, backpropagation neural network, strategi evolusi.

  11. Agent-based models of strategies for the emergence and evolution of grammatical agreement.

    Directory of Open Access Journals (Sweden)

    Katrien Beuls

    Full Text Available Grammatical agreement means that features associated with one linguistic unit (for example number or gender become associated with another unit and then possibly overtly expressed, typically with morphological markers. It is one of the key mechanisms used in many languages to show that certain linguistic units within an utterance grammatically depend on each other. Agreement systems are puzzling because they can be highly complex in terms of what features they use and how they are expressed. Moreover, agreement systems have undergone considerable change in the historical evolution of languages. This article presents language game models with populations of agents in order to find out for what reasons and by what cultural processes and cognitive strategies agreement systems arise. It demonstrates that agreement systems are motivated by the need to minimize combinatorial search and semantic ambiguity, and it shows, for the first time, that once a population of agents adopts a strategy to invent, acquire and coordinate meaningful markers through social learning, linguistic self-organization leads to the spontaneous emergence and cultural transmission of an agreement system. The article also demonstrates how attested grammaticalization phenomena, such as phonetic reduction and conventionalized use of agreement markers, happens as a side effect of additional economizing principles, in particular minimization of articulatory effort and reduction of the marker inventory. More generally, the article illustrates a novel approach for studying how key features of human languages might emerge.

  12. Fusing enacted and expected mimicry generates a winning strategy that promotes the evolution of cooperation.

    Science.gov (United States)

    Fischer, Ilan; Frid, Alex; Goerg, Sebastian J; Levin, Simon A; Rubenstein, Daniel I; Selten, Reinhard

    2013-06-18

    Although cooperation and trust are essential features for the development of prosperous populations, they also put cooperating individuals at risk for exploitation and abuse. Empirical and theoretical evidence suggests that the solution to the problem resides in the practice of mimicry and imitation, the expectation of opponent's mimicry and the reliance on similarity indices. Here we fuse the principles of enacted and expected mimicry and condition their application on two similarity indices to produce a model of mimicry and relative similarity. Testing the model in computer simulations of behavioral niches, populated with agents that enact various strategies and learning algorithms, shows how mimicry and relative similarity outperforms all the opponent strategies it was tested against, pushes noncooperative opponents toward extinction, and promotes the development of cooperative populations. The proposed model sheds light on the evolution of cooperation and provides a blueprint for intentional induction of cooperation within and among populations. It is suggested that reducing conflict intensities among human populations necessitates (i) instigation of social initiatives that increase the perception of similarity among opponents and (ii) efficient lowering of the similarity threshold of the interaction, the minimal level of similarity that makes cooperation advisable.

  13. Surface spintronics enhanced photo-catalytic hydrogen evolution: Mechanisms, strategies, challenges and future

    Science.gov (United States)

    Zhang, Wenyan; Gao, Wei; Zhang, Xuqiang; Li, Zhen; Lu, Gongxuan

    2018-03-01

    Hydrogen is a green energy carrier with high enthalpy and zero environmental pollution emission characteristics. Photocatalytic hydrogen evolution (HER) is a sustainable and promising way to generate hydrogen. Despite of great achievements in photocatalytic HER research, its efficiency is still limited due to undesirable electron transfer loss, high HER over-potential and low stability of some photocatalysts, which lead to their unsatisfied performance in HER and anti-photocorrosion properties. In recent years, many spintronics works have shown their enhancing effects on photo-catalytic HER. For example, it was reported that spin polarized photo-electrons could result in higher photocurrents and HER turn-over frequency (up to 200%) in photocatalytic system. Two strategies have been developed for electron spin polarizing, which resort to heavy atom effect and magnetic induction respectively. Both theoretical and experimental studies show that controlling spin state of OHrad radicals in photocatalytic reaction can not only decrease OER over-potential (even to 0 eV) of water splitting, but improve stability and charge lifetime of photocatalysts. A convenient strategy have been developed for aligning spin state of OHrad by utilizing chiral molecules to spin filter photo-electrons. By chiral-induced spin filtering, electron polarization can approach to 74%, which is significantly larger than some traditional transition metal devices. Those achievements demonstrate bright future of spintronics in enhancing photocatalytic HER, nevertheless, there is little work systematically reviewing and analysis this topic. This review focuses on recent achievements of spintronics in photocatalytic HER study, and systematically summarizes the related mechanisms and important strategies proposed. Besides, the challenges and developing trends of spintronics enhanced photo-catalytic HER research are discussed, expecting to comprehend and explore such interdisciplinary research in

  14. Expanding the Enzyme Universe: Accessing Non-Natural Reactions by Mechanism-Guided Directed Evolution

    Science.gov (United States)

    Renata, Hans; Wang, Z. Jane

    2015-01-01

    High selectivities and exquisite control over reaction outcomes entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature’s known repertoire. We will use this review to outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progressions have been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been discovered and exploited for chemical synthesis, emphasizing reactions that do not have natural counterparts. The new functions have mechanistic parallels to the native reaction mechanisms that often manifest as catalytic promiscuity and the ability to convert from one function to the other with minimal mutation. We present examples of how non-natural activities have been improved by directed evolution, mimicking the process used by nature to create new catalysts. Examples of new enzyme functions include epoxide opening reactions with non-natural nucleophiles catalyzed by a laboratory-evolved halohydrin dehalogenase, cyclopropanation and other carbene transfer reactions catalyzed by cytochrome P450 variants, and non-natural modes of cyclization by a modified terpene synthase. Lastly, we describe discoveries of non-native catalytic functions that may provide future opportunities for expanding the enzyme universe. PMID:25649694

  15. Luminescence evolution from alumina ceramic surface before flashover under direct and alternating current voltage in vacuum

    Energy Technology Data Exchange (ETDEWEB)

    Su, Guo-Qiang; Wang, Yi-Bo; Song, Bai-Peng; Mu, Hai-Bao, E-mail: haibaomu@xjtu.edu.cn, E-mail: gjzhang@xjtu.edu.cn; Zhang, Guan-Jun, E-mail: haibaomu@xjtu.edu.cn, E-mail: gjzhang@xjtu.edu.cn [State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Li, Feng; Wang, Meng [Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China)

    2016-06-15

    The luminescence evolution phenomena from alumina ceramic surface in vacuum under high voltage of direct and alternating current are reported, with the voltage covering a large range from far below to close to the flashover voltage. Its time resolved and spatial distributed behaviors are examined by a photon counting system and an electron-multiplying charge-coupled device (EMCCD) together with a digital camera, respectively. The luminescence before flashover exhibits two stages as voltage increasing, i.e., under a relative low voltage (Stage A), the luminescence is ascribed to radiative recombination of hetero-charges injected into the sample surface layer by Schottky effect; under a higher voltage (Stage B), a stable secondary electron emission process, resulting from the Fowler-Nordheim emission at the cathode triple junction (CTJ), is responsible for the luminescence. Spectrum analysis implies that inner secondary electrons within the surface layer of alumina generated during the SSEE process also participate in the luminescence of Stage B. A comprehensive interpretation of the flashover process is formulated, which might promote a better understanding of flashover issue in vacuum.

  16. Directed evolution of a model primordial enzyme provides insights into the development of the genetic code.

    Directory of Open Access Journals (Sweden)

    Manuel M Müller

    Full Text Available The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.

  17. HIV Surveillance Among Pregnant Women Attending Antenatal Clinics: Evolution and Current Direction.

    Science.gov (United States)

    Dee, Jacob; Garcia Calleja, Jesus M; Marsh, Kimberly; Zaidi, Irum; Murrill, Christopher; Swaminathan, Mahesh

    2017-12-05

    Since the late 1980s, human immunodeficiency virus (HIV) sentinel serosurveillance among pregnant women attending select antenatal clinics (ANCs) based on unlinked anonymous testing (UAT) has provided invaluable information for tracking HIV prevalence and trends and informing global and national HIV models in most countries with generalized HIV epidemics. However, increased coverage of HIV testing, prevention of mother-to-child transmission (PMTCT), and antiretroviral therapy has heightened ethical concerns about UAT. PMTCT programs now routinely collect demographic and HIV testing information from the same pregnant women as serosurveillance and therefore present an alternative to UAT-based ANC serosurveillance. This paper reports on the evolution and current direction of the global approach to HIV surveillance among pregnant women attending ANCs, including the transition away from traditional UAT-based serosurveillance and toward new guidance from the World Health Organization and the Joint United Nations Programme on HIV/AIDS on the implementation of surveillance among pregnant women attending ANCs based on routine PMTCT program data. ©Jacob Dee, Jesus M Garcia Calleja, Kimberly Marsh, Irum Zaidi, Christopher Murrill, Mahesh Swaminathan. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 05.12.2017.

  18. Using directed evolution to probe the substrate specificity of mandelamide hydrolase.

    Science.gov (United States)

    Wang, Pan-Fen; Yep, Alejandra; Kenyon, George L; McLeish, Michael J

    2009-02-01

    Mandelamide hydrolase (MAH), a member of the amidase signature family, catalyzes the hydrolysis of mandelamide to mandelate and ammonia. X-ray structures of several members of this family, but not that of MAH, have been reported. These reveal nearly superimposable conformations of the unusual Ser-cisSer-Lys catalytic triad. Conversely, the residues involved in substrate recognition are not conserved, implying that the binding pocket could be modified to change the substrate specificity, perhaps by directed evolution. Here we show that MAH is able to hydrolyze small aliphatic substrates such as lactamide, albeit with low efficiency. A selection method to monitor changes in mandelamide/lactamide preference was developed and used to identify several mutations affecting substrate binding. A homology model places some of these mutations close to the catalytic triad, presumably in the MAH active site. In particular, Gly202 appears to control the preference for aromatic substrates as the G202A variant showed three orders of magnitude decrease in k(cat)/K(m) for (R)- and (S)-mandelamide. This reduction in activity increased to six orders of magnitude for the G202V variant.

  19. THE EVOLUTION OF FOREIGN DIRECT INVESTMENT THEORIES: HOW CAN INSTITUTIONS RELATE?

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Bényei

    2016-07-01

    Full Text Available Theories of Foreign Direct Investment (FDI have evolved over the past few decades. There are theories which try to explain the motivation behind investments, and there are others to explain why companies go abroad. To understand the motivations of firms in today’s economic environment, we have to trace the evolution of these theories. At first, researchers tried to explain capital movements with trade theories. However, because of the strict conditionality, they only explained a small part of FDI. To extend the validity of the models, researchers started to examine investments from the firms’ point of view. The models evolved from Vernon’s product life cycle model, through Hymer’s monopolistic advantage model, to Dunning’s eclectic theory. These firm-based theories highlighted the importance of entrepreneurs. Dunning’s theory includes the statements which featured in previous models. We can find monopolistic advantage, localization and internalization models in this argument. This study is an attempt to relate the issue of FDI to institutions. There is a rapidly growing literature on the subject of new institutional economics, which indicates that the effect of institutions can appear in any economic situation. These effects can be shown in Dunning’s theory, too. The consensus view seems to be that institutions play a significant role in ownership, in localization and in internalization advantages. Consequently, we can find them in the other models, too. The purpose of this paper is to ident

  20. Identification of a carotenoid oxygenase synthesizing acyclic xanthophylls: combinatorial biosynthesis and directed evolution.

    Science.gov (United States)

    Mijts, Benjamin N; Lee, Pyung Cheon; Schmidt-Dannert, Claudia

    2005-04-01

    A carotenoid desaturase homolog from Staphylococcus aureus (CrtOx) was identified. When expressed in engineered E. coli cells synthesizing linear C(30) carotenoids, polar carotenoid products were generated, identified as aldehyde and carboxylic acid C(30) carotenoid derivatives. The major product in this engineered pathway is the fully desaturated C(30) dialdehyde carotenoid 4,4'-diapolycopen-4,4'-dial. Very low carotenoid yields were observed when CrtOx was complemented with the C(40) carotenoid lycopene pathway. But extension of an in vitro evolved pathway of the fully desaturated 2,4,2',4'-tetradehydrolycopene produced the structurally novel fully desaturated C(40) dialdehyde carotenoid 2,4,2',4'-tetradehydrolycopendial. Directed evolution of CrtOx by error-prone PCR resulted in a number of variants with higher activity on C(40) carotenoid substrates and improved product profiles. These findings may provide new biosynthetic routes to highly polar carotenoids with unique spectral properties desirable for a number of industrial and pharmaceutical applications.

  1. Moving in the Right Direction: Evolution of Protein Structural Vibrations with Functional State and Mutation

    Science.gov (United States)

    Niessen, Katherine; Xu, Mengyang; Snell, Edward; Markelz, Andrea

    Long-range intramolecular vibrations may enable efficient access to functionally important conformations. We examine how these motions change with inhibitor binding and mutation using terahertz anisotropic absorption and molecular modeling. The measured anisotropic absorption dramatically changes with 3NAG inhibitor binding for wild type (WT) free chicken egg white lysozyme (CEWL). We examine the evolution of internal motions with binding using normal mode analysis to calculate an ensemble averaged vibrational density of states (VDOS) and isotropic and anisotropic absorptions for both WT and a two residue (R14 and H15) deletion mutant which has a 1.4 higher activity rate. While the VDOS and isotropic response are largely unchanged with inhibitor binding, the anisotropic response changes dramatically with binding. However, for the mutant the calculated unbound anisotropic absorption more closely resembles its bound spectrum, and it has increased calculated mean squared fluctuations in regions overlapping those in its bound state. These results indicate that the mutant's enhanced activity may be due to a shift in the direction of vibrations toward those of the bound state, increasing the sampling rate of the bound conformation.

  2. Strategy Dynamics through a Demand-Based Lens: The Evolution of Market Boundaries, Resource Rents and Competitive Positions

    OpenAIRE

    Adner, Ron; Zemsky, Peter

    2003-01-01

    We develop a novel approach to the dynamics of business strategy that is grounded in an explicit treatment of consumer choice when technologies improve over time. We address the evolution of market boundaries, resource rents and competitive positions by adapting models of competition with differentiated products. Our model is consistent with the central strategy assertion that competitive interactions are governed by superior value creation and competitive advantage. More importantly, it show...

  3. Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

    KAUST Repository

    Shi, Yanshu; Cairns, Amy; Liu, Yunling; Belmabkhout, Youssef; Cai, Xuechao; Pang, Maolin; Eddaoudi, Mohamed

    2017-01-01

    In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

  4. Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

    KAUST Repository

    Shi, Yanshu

    2017-06-23

    In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

  5. Computing Gowdy spacetimes via spectral evolution in future and past directions

    International Nuclear Information System (INIS)

    Amorim, Paulo; Bernardi, Christine; LeFloch, Philippe G

    2009-01-01

    We consider a system of nonlinear wave equations with constraints that arises from the Einstein equations of general relativity and describes the geometry of the so-called Gowdy symmetric spacetimes on T 3 . We introduce two numerical methods, which are based on the pseudo-spectral approximation. The first approach relies on marching in the future timelike direction and toward the singularity t = 0 and is based on a novel nonlinear transformation, which allows us to reduce the nonlinear source terms to simple quadratic products of the unknown variables. The second approach is designed from asymptotic formulae that are available near this singularity, and evolves the solutions in the past timelike direction from the 'final' data given at t = 0. Numerical experiments are presented in various regimes, including cases where 'spiky' structures are observed as the singularity is approached. The proposed backward strategy leads to a robust numerical method which allows us to accurately simulate the long-time behavior of a large class of Gowdy spacetimes.

  6. Direct fitness of group living mammals varies with breeding strategy, climate and fitness estimates.

    Science.gov (United States)

    Ebensperger, Luis A; Rivera, Daniela S; Hayes, Loren D

    2012-09-01

    1. Understanding how variation in fitness relates to variation in group living remains critical to determine whether this major aspect of social behaviour is currently adaptive. 2. Available evidence in social mammals aimed to examine this issue remains controversial. Studies show positive (i.e. potentially adaptive), neutral or even negative fitness effects of group living. 3. Attempts to explain this variation rely on intrinsic and extrinsic factors to social groups. Thus, relatively more positive fitness effects are predicted in singularly breeding as opposed to plural breeding species. Fitness effects of sociality in turn may depend on ecological conditions (i.e. extrinsic factors) that influence associated benefits and costs. 4. We used meta-analytic tools to review how breeding strategy or ecological conditions influence the effect size associated with direct fitness-sociality relationships reported in the mammalian literature. Additionally, we determined how taxonomic affiliation of species studied, different fitness and sociality measures used, and major climatic conditions of study sites explained any variation in direct fitness effect size. 5. We found group living had modest, yet positive effects on direct fitness. This generally adaptive scenario was contingent not only upon breeding strategy and climate of study sites, but also on fitness measures examined. Thus, positive and significant effects characterized singular as opposed to plural breeding strategies. 6. We found more positive fitness effects on studies conducted in tropical as opposed to temperate or arid climates. More positive and significant effects were noted on studies that relied on group fecundity, male fecundity and offspring survival as measures of fitness. 7. To conclude, direct fitness consequences of mammalian group living are driven by interspecific differences in breeding strategy and climate conditions. Other factors not examined in this study, namely individual variation in

  7. Flexibility to contingency changes distinguishes habitual and goal-directed strategies in humans.

    Science.gov (United States)

    Lee, Julie J; Keramati, Mehdi

    2017-09-01

    Decision-making in the real world presents the challenge of requiring flexible yet prompt behavior, a balance that has been characterized in terms of a trade-off between a slower, prospective goal-directed model-based (MB) strategy and a fast, retrospective habitual model-free (MF) strategy. Theory predicts that flexibility to changes in both reward values and transition contingencies can determine the relative influence of the two systems in reinforcement learning, but few studies have manipulated the latter. Therefore, we developed a novel two-level contingency change task in which transition contingencies between states change every few trials; MB and MF control predict different responses following these contingency changes, allowing their relative influence to be inferred. Additionally, we manipulated the rate of contingency changes in order to determine whether contingency change volatility would play a role in shifting subjects between a MB and MF strategy. We found that human subjects employed a hybrid MB/MF strategy on the task, corroborating the parallel contribution of MB and MF systems in reinforcement learning. Further, subjects did not remain at one level of MB/MF behaviour but rather displayed a shift towards more MB behavior over the first two blocks that was not attributable to the rate of contingency changes but rather to the extent of training. We demonstrate that flexibility to contingency changes can distinguish MB and MF strategies, with human subjects utilizing a hybrid strategy that shifts towards more MB behavior over blocks, consequently corresponding to a higher payoff.

  8. "Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Lukas Fenner

    Full Text Available Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as "Beijing" has repeatedly been associated with drug resistance and has been emerging in some parts of the world. "Beijing" strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC strains exhibiting the typical "Beijing" spoligotyping pattern.MTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS rather than to Lineage 2 (also known as East-Asian lineage. Sequencing of the RD207 in one of these strains showed that the deletion responsible for this "Pseudo-Beijing" spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical "Beijing" strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR region of MTBC.We provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of "Beijing" strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes.

  9. Footprints of directional selection in wild Atlantic salmon populations: evidence for parasite-driven evolution?

    Science.gov (United States)

    Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Lien, Sigbjørn; Primmer, Craig R

    2014-01-01

    Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved.

  10. Improving the thermal stability of cellobiohydrolase Cel7A from Hypocrea jecorina by directed evolution.

    Science.gov (United States)

    Goedegebuur, Frits; Dankmeyer, Lydia; Gualfetti, Peter; Karkehabadi, Saeid; Hansson, Henrik; Jana, Suvamay; Huynh, Vicky; Kelemen, Bradley R; Kruithof, Paulien; Larenas, Edmund A; Teunissen, Pauline J M; Ståhlberg, Jerry; Payne, Christina M; Mitchinson, Colin; Sandgren, Mats

    2017-10-20

    Secreted mixtures of Hypocrea jecorina cellulases are able to efficiently degrade cellulosic biomass to fermentable sugars at large, commercially relevant scales. H. jecorina Cel7A, cellobiohydrolase I, from glycoside hydrolase family 7, is the workhorse enzyme of the process. However, the thermal stability of Cel7A limits its use to processes where temperatures are no higher than 50 °C. Enhanced thermal stability is desirable to enable the use of higher processing temperatures and to improve the economic feasibility of industrial biomass conversion. Here, we enhanced the thermal stability of Cel7A through directed evolution. Sites with increased thermal stability properties were combined, and a Cel7A variant (FCA398) was obtained, which exhibited a 10.4 °C increase in T m and a 44-fold greater half-life compared with the wild-type enzyme. This Cel7A variant contains 18 mutated sites and is active under application conditions up to at least 75 °C. The X-ray crystal structure of the catalytic domain was determined at 2.1 Å resolution and showed that the effects of the mutations are local and do not introduce major backbone conformational changes. Molecular dynamics simulations revealed that the catalytic domain of wild-type Cel7A and the FCA398 variant exhibit similar behavior at 300 K, whereas at elevated temperature (475 and 525 K), the FCA398 variant fluctuates less and maintains more native contacts over time. Combining the structural and dynamic investigations, rationales were developed for the stabilizing effect at many of the mutated sites. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Biodegradation of 1,2,3-trichloropropane through directed evolution and heterologous expression of a haloalkane dehalogenase gene.

    Science.gov (United States)

    Bosma, Tjibbe; Damborský, Jirí; Stucki, Gerhard; Janssen, Dick B

    2002-07-01

    Using a combined strategy of random mutagenesis of haloalkane dehalogenase and genetic engineering of a chloropropanol-utilizing bacterium, we constructed an organism that is capable of growth on 1,2,3-trichloropropane (TCP). This highly toxic and recalcitrant compound is a waste product generated from the manufacture of the industrial chemical epichlorohydrin. Attempts to select and enrich bacterial cultures that can degrade TCP from environmental samples have repeatedly been unsuccessful, prohibiting the development of a biological process for groundwater treatment. The critical step in the aerobic degradation of TCP is the initial dehalogenation to 2,3-dichloro-1-propanol. We used random mutagenesis and screening on eosin-methylene blue agar plates to improve the activity on TCP of the haloalkane dehalogenase from Rhodococcus sp. m15-3 (DhaA). A second-generation mutant containing two amino acid substitutions, Cys176Tyr and Tyr273Phe, was nearly eight times more efficient in dehalogenating TCP than wild-type dehalogenase. Molecular modeling of the mutant dehalogenase indicated that the Cys176Tyr mutation has a global effect on the active-site structure, allowing a more productive binding of TCP within the active site, which was further fine tuned by Tyr273Phe. The evolved haloalkane dehalogenase was expressed under control of a constitutive promoter in the 2,3-dichloro-1-propanol-utilizing bacterium Agrobacterium radiobacter AD1, and the resulting strain was able to utilize TCP as the sole carbon and energy source. These results demonstrated that directed evolution of a key catabolic enzyme and its subsequent recruitment by a suitable host organism can be used for the construction of bacteria for the degradation of a toxic and environmentally recalcitrant chemical.

  12. Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming.

    Science.gov (United States)

    Budniatzky, Inbar; Gepstein, Lior

    2014-04-01

    Myocardial cell-replacement therapies are emerging as novel therapeutic paradigms for myocardial repair but are hampered by the lack of sources of autologous human cardiomyocytes. The recent advances in stem cell biology and in transcription factor-based reprogramming strategies may provide exciting solutions to this problem. In the current review, we describe the different reprogramming strategies that can give rise to cardiomyocytes for regenerative medicine purposes. Initially, we describe induced pluripotent stem cell technology, a method by which adult somatic cells can be reprogrammed to yield pluripotent stem cells that could later be coaxed ex vivo to differentiate into cardiomyocytes. The generated induced pluripotent stem cell-derived cardiomyocytes could then be used for myocardial cell transplantation and tissue engineering strategies. We also describe the more recent direct reprogramming approaches that aim to directly convert the phenotype of one mature cell type (fibroblast) to another (cardiomyocyte) without going through a pluripotent intermediate cell type. The advantages and shortcomings of each strategy for cardiac regeneration are discussed, along with the hurdles that need to be overcome on the road to clinical translation.

  13. Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

    Science.gov (United States)

    Leininger, Elizabeth C; Kelley, Darcy B

    2013-04-07

    Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors.

  14. Evolution of post-deployment indicators of oral health on the Family Health Strategy

    Science.gov (United States)

    Palacio, Danielle da Costa; Vazquez, Fabiana de Lima; Ramos, Danielle Viana Ribeiro; Peres, Stela Verzinhasse; Pereira, Antonio Carlos; Guerra, Luciane Miranda; Cortellazzi, Karine Laura; Bulgareli, Jaqueline Vilela

    2014-01-01

    Objective To evaluate the evolution of indicators after the implementation of 21 Oral Healthcare Teams in the Family Health Strategy. Methods We used data from outpatient services of Oral Healthcare Teams to evaluate efficiency, access, percentage of absences and emergencies of oral healthcare professionals who worked in the partnership between the Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein and the Secretaria Municipal de Saúde de São Paulo, during the period 2009-2011. Results Percentages of emergencies, income, and access showed a significant difference during the period analyzed, but no difference for percentage of absences was found. When monthly analysis was made, it is noteworthy that at the beginning of service implementation a fluctuation occurred, which may indicate that the work was consolidated over the months, becoming capable of receiving new professionals and increasing the population served. Comparison of the indicators in that period with the goals agreed upon between the Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein and the Secretaria Municipal de Saúde de São Paulo made it possible to notice that the Oral Health Teams had a good performance. Conclusion The results showed that the goals were achieved reflecting the increasing number of professionals, the maturing of work processes in the Oral Health Teams, and optimization of the manpower available to perform the activities. Understanding these results will be important to guide the actions of Oral Health Teams for the following years and to assess the achievement of goals. PMID:25295445

  15. Governance of sustainable development: co-evolution of corporate and political strategies

    International Nuclear Information System (INIS)

    Bleischwitz, R.; College of Europe, Bruges

    2004-01-01

    This article proposes a policy framework for analysing corporate governance toward sustainable development. The aim is to set up a framework for analysing market evolution toward sustainability. In the first section, the paper briefly refers to recent theories about both market and government failures that express scepticism about the way that framework conditions for market actors are set. For this reason, multi-layered governance structures seem advantageous if new solutions are to be developed in policy areas concerned with long-term change and stepwise internalisation of externalities. The paper introduces the principle of regulated self-regulation. With regard to corporate actors' interests, it presents recent insights from theories about the knowledge-based firm, where the creation of new knowledge is based on the absorption of societal views. The result is greater scope for the endogenous internalisation of externalities, which leads to a variety of new and different corporate strategies. Because governance has to set incentives for quite a diverse set of actors in their daily operations, the paper finally discusses innovation-inducing regulation. In both areas, regulated self-regulation and innovation-inducing regulation, corporate and political governance co-evolve. The paper concludes that these co-evolutionary mechanisms may assume some of the stabilising and orientating functions previously exercised by framing activities of the state. In such a view, the government's main function is to facilitate learning processes, thus departing from the state's function as known from welfare economics. (author)

  16. Endocasts-the direct evidence and recent advances in the study of human brain evolution

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Brain evolution is one of the most important aspects of human evolution, usually studied through endocasts. Analysis of fossil hominid endocasts allows inferences on functional anatomy, physiology, and phylogeny. In this paper, we describe the general features of endocast studies and review some of the major topics in paleoneurology. These are: absolute and relative brain size evolution; brain shape variation; brain asymmetry and lateralization; middle meningeal vessels and venous sinuses; application of computed tomography and virtual imaging; the history of Chinese brain endocast studies. In particular, this review emphasizes endocast studies on Chinese hominin fossils.

  17. Depressurization as an accident management strategy to minimize the consequences of direct containment heating

    International Nuclear Information System (INIS)

    Hanson, D.J.; Golden, D.W.; Chambers, R.; Miller, J.D.; Hallbert, B.P.; Dobbe, C.A.

    1990-10-01

    Probabilistic Risk Assessments (PRAs) have identified severe accidents for nuclear power plants that have the potential to cause failure of the containment through direct containment heating (DCH). Prevention of DCH or mitigation of its effects may be possible using accident management strategies that intentionally depressurize the reactor coolant system (RCS). The effectiveness of intentional depressurization during a station blackout TMLB' sequence was evaluated considering the phenomenological behavior, hardware performance, and operational performance. Phenomenological behavior was calculated using the SCDAP/RELAP5 severe accident analysis code. Two strategies to mitigate DCH by depressurization of the RCS were considered. One strategy, called early depressurization, assumed that the reactor head vent and pressurizer power-operated relief valves (PORVs) were latched open at steam generator dryout. The second strategy, called late depression, assumed that the head vent and PORVs were latched open at a core exit temperature of ∼922 K (1200 degree F). Depressurization of the RCS to a low value that may mitigate DCH was predicted prior to reactor pressure vessel breach for both early and late depressurization. The strategy of late depressurization is preferred over early depressurization because there are greater opportunities to recover plant functions prior to core damage and because failure uncertainties are lessened. 22 refs., 38 figs., 6 tabs

  18. Depressurization as an accident management strategy to minimize the consequences of direct containment heating

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, D.J.; Golden, D.W.; Chambers, R.; Miller, J.D.; Hallbert, B.P.; Dobbe, C.A. (EG and G Idaho, Inc., Idaho Falls, ID (USA))

    1990-10-01

    Probabilistic Risk Assessments (PRAs) have identified severe accidents for nuclear power plants that have the potential to cause failure of the containment through direct containment heating (DCH). Prevention of DCH or mitigation of its effects may be possible using accident management strategies that intentionally depressurize the reactor coolant system (RCS). The effectiveness of intentional depressurization during a station blackout TMLB' sequence was evaluated considering the phenomenological behavior, hardware performance, and operational performance. Phenomenological behavior was calculated using the SCDAP/RELAP5 severe accident analysis code. Two strategies to mitigate DCH by depressurization of the RCS were considered. One strategy, called early depressurization, assumed that the reactor head vent and pressurizer power-operated relief valves (PORVs) were latched open at steam generator dryout. The second strategy, called late depression, assumed that the head vent and PORVs were latched open at a core exit temperature of {approximately}922 K (1200{degree}F). Depressurization of the RCS to a low value that may mitigate DCH was predicted prior to reactor pressure vessel breach for both early and late depressurization. The strategy of late depressurization is preferred over early depressurization because there are greater opportunities to recover plant functions prior to core damage and because failure uncertainties are lessened. 22 refs., 38 figs., 6 tabs.

  19. Implementing the European Marine Strategy Framework Directive: Scientific challenges and opportunities

    Science.gov (United States)

    Newton, Alice; Borja, Angel; Solidoro, Cosimo; Grégoire, Marilaure

    2015-10-01

    The Marine Strategy Framework Directive (MSFD; EC, 2008) is an ambitious European policy instrument that aims to achieve Good Environmental Status (GES) in the 5,720,000 km2 of European seas by 2020, using an Ecosystem Approach. GES is to be assessed using 11 descriptors and up to 56 indicators (European Commission, 2010), and the goal is for clean, healthy and productive seas that are the basis for marine-based development, known as Blue-Growth. The MSFD is one of many policy instruments, such as the Water Framework Directive, the Common Fisheries Policy and the Habitats Directive that, together, should result in "Healthy Oceans and Productive Ecosystems - HOPE". Researchers working together with stakeholders such as the Member States environmental agencies, the European Environmental Agency, and the Regional Sea Conventions, are to provide the scientific knowledge basis for the implementation of the MSFD. This represents both a fascinating challenge and a stimulating opportunity.

  20. Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

    Science.gov (United States)

    Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

    2005-01-01

    The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

  1. A STUDY ON STUDENTS’ DIRECT LISTENING STRATEGIES IN COMPREHENDING A PASSAGE AT THE SECOND GRADE STUDENTS OF SMAN OLAHRAGA RIAU

    Directory of Open Access Journals (Sweden)

    Kurniawan Kurniawan

    2016-04-01

    Full Text Available The purpose of this research was to identify the students’ directlistening strategies in comprehending a passage at the second grade students ofSMAN Olahraga Riau. The design of this research was survey attitudes andpractices. Sample of the research was 50 students at the second grade students ofSMAN Olahraga Riau. The instrument that was used was questionnaire. Thequestionnaire was design the students’ direct listening. The questionnaire wasanalyzed by using descriptive statistics and Likert scale. The result of analyzingdata in terms of memory strategy, the students’ mean score was 3.99 in moderatelevel. In terms of cognitive strategy, the students’ mean score was 3.74 inmoderate level, while in terms of compensation strategy, the students had meanscore 3.86 in moderate level. In conclusion, the students were interested usingmemory strategy as the main direct strategy in comprehending a passage at thesecond grade students of SMAN Olahraga Riau.Keywords : Direct Listening Strategy, Comprehension, and Passage

  2. Direct Detection of Protein Biomarkers in Human Fluids Using Site-Specific Antibody Immobilization Strategies

    Directory of Open Access Journals (Sweden)

    Maria Soler

    2014-01-01

    Full Text Available Design of an optimal surface biofunctionalization still remains an important challenge for the application of biosensors in clinical practice and therapeutic follow-up. Optical biosensors offer real-time monitoring and highly sensitive label-free analysis, along with great potential to be transferred to portable devices. When applied in direct immunoassays, their analytical features depend strongly on the antibody immobilization strategy. A strategy for correct immobilization of antibodies based on the use of ProLinker™ has been evaluated and optimized in terms of sensitivity, selectivity, stability and reproducibility. Special effort has been focused on avoiding antibody manipulation, preventing nonspecific adsorption and obtaining a robust biosurface with regeneration capabilities. ProLinker™-based approach has demonstrated to fulfill those crucial requirements and, in combination with PEG-derivative compounds, has shown encouraging results for direct detection in biological fluids, such as pure urine or diluted serum. Furthermore, we have implemented the ProLinker™ strategy to a novel nanoplasmonic-based biosensor resulting in promising advantages for its application in clinical and biomedical diagnosis.

  3. Coordinated Low Voltage Ride through strategies for Permanent Magnet Direct Drive Synchronous Generators

    Directory of Open Access Journals (Sweden)

    Zhang Ge

    2016-01-01

    Full Text Available By analyzing the mechanism of the low voltage ride through on the permanent magnet direct drive synchronous wind power generating units, this paper proposes a coordinated control strategy for permanent magnet synchronous generator. In order to avoid over speed operation of the generation units, over voltage on DC capacitor and over current on convert, the improved pitch angle control and inverter control are used. When the grid voltage drops, the captured wind power is cut down by the variable pitch system, which limits the speed of the generator, the generator side converter keeps the DC capacitor voltage stabile; and the grid side converter provides reactive power to the grid to help the grid voltage recover. The control strategy does not require any additional hardware equipment, with existing control means, the unit will be able to realize low voltage ride through. Finally, based on Matlab/Simulink to build permanent magnet direct drive wind power generation system, the simulation results verify the correctness and effectiveness of the control strategy.

  4. Direct detection of protein biomarkers in human fluids using site-specific antibody immobilization strategies.

    Science.gov (United States)

    Soler, Maria; Estevez, M-Carmen; Alvarez, Mar; Otte, Marinus A; Sepulveda, Borja; Lechuga, Laura M

    2014-01-29

    Design of an optimal surface biofunctionalization still remains an important challenge for the application of biosensors in clinical practice and therapeutic follow-up. Optical biosensors offer real-time monitoring and highly sensitive label-free analysis, along with great potential to be transferred to portable devices. When applied in direct immunoassays, their analytical features depend strongly on the antibody immobilization strategy. A strategy for correct immobilization of antibodies based on the use of ProLinker™ has been evaluated and optimized in terms of sensitivity, selectivity, stability and reproducibility. Special effort has been focused on avoiding antibody manipulation, preventing nonspecific adsorption and obtaining a robust biosurface with regeneration capabilities. ProLinker™-based approach has demonstrated to fulfill those crucial requirements and, in combination with PEG-derivative compounds, has shown encouraging results for direct detection in biological fluids, such as pure urine or diluted serum. Furthermore, we have implemented the ProLinker™ strategy to a novel nanoplasmonic-based biosensor resulting in promising advantages for its application in clinical and biomedical diagnosis.

  5. Regenerating the human heart: direct reprogramming strategies and their current limitations.

    Science.gov (United States)

    Ghiroldi, Andrea; Piccoli, Marco; Ciconte, Giuseppe; Pappone, Carlo; Anastasia, Luigi

    2017-10-27

    Cardiovascular diseases are the leading cause of death in the Western world. Unfortunately, current therapies are often only palliative, consequently essentially making heart transplantation necessary for many patients. However, several novel therapeutic approaches in the past two decades have yielded quite encouraging results. The generation of induced pluripotent stem cells, through the forced expression of stem cell-specific transcription factors, has inspired the most promising strategies for heart regeneration by direct reprogramming of cardiac fibroblasts into functional cardiomyocytes. Initial attempts at this reprogramming were conducted using a similar approach to the one used with transcription factors, but during years, novel strategies have been tested, e.g., miRNAs, recombinant proteins and chemical molecules. Although preliminary results on animal models are promising, the low reprogramming efficiency, as well as the incomplete maturation of the cardiomyocytes, still represents important obstacles. This review covers direct transdifferentiation strategies that have been proposed and developed and illustrates the pros and cons of each approach. Indeed, as described in the manuscript, there are still many unanswered questions and drawbacks that require a better understanding of the basic signaling pathways and transcription factor networks before functional cells, suitable for cardiac regeneration and safe for the patients, can be generated and used for human therapies.

  6. Comparing Different Strategies in Directed Evolution of Enzyme Stereoselectivity: Single- versus Double-Code Saturation Mutagenesis.

    Science.gov (United States)

    Sun, Zhoutong; Lonsdale, Richard; Li, Guangyue; Reetz, Manfred T

    2016-10-04

    Saturation mutagenesis at sites lining the binding pockets of enzymes constitutes a viable protein engineering technique for enhancing or inverting stereoselectivity. Statistical analysis shows that oversampling in the screening step (the bottleneck) increases astronomically as the number of residues in the randomization site increases, which is the reason why reduced amino acid alphabets have been employed, in addition to splitting large sites into smaller ones. Limonene epoxide hydrolase (LEH) has previously served as the experimental platform in these methodological efforts, enabling comparisons between single-code saturation mutagenesis (SCSM) and triple-code saturation mutagenesis (TCSM); these employ either only one or three amino acids, respectively, as building blocks. In this study the comparative platform is extended by exploring the efficacy of double-code saturation mutagenesis (DCSM), in which the reduced amino acid alphabet consists of two members, chosen according to the principles of rational design on the basis of structural information. The hydrolytic desymmetrization of cyclohexene oxide is used as the model reaction, with formation of either (R,R)- or (S,S)-cyclohexane-1,2-diol. DCSM proves to be clearly superior to the likewise tested SCSM, affording both R,R- and S,S-selective mutants. These variants are also good catalysts in reactions of further substrates. Docking computations reveal the basis of enantioselectivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Flexibility to contingency changes distinguishes habitual and goal-directed strategies in humans.

    Directory of Open Access Journals (Sweden)

    Julie J Lee

    2017-09-01

    Full Text Available Decision-making in the real world presents the challenge of requiring flexible yet prompt behavior, a balance that has been characterized in terms of a trade-off between a slower, prospective goal-directed model-based (MB strategy and a fast, retrospective habitual model-free (MF strategy. Theory predicts that flexibility to changes in both reward values and transition contingencies can determine the relative influence of the two systems in reinforcement learning, but few studies have manipulated the latter. Therefore, we developed a novel two-level contingency change task in which transition contingencies between states change every few trials; MB and MF control predict different responses following these contingency changes, allowing their relative influence to be inferred. Additionally, we manipulated the rate of contingency changes in order to determine whether contingency change volatility would play a role in shifting subjects between a MB and MF strategy. We found that human subjects employed a hybrid MB/MF strategy on the task, corroborating the parallel contribution of MB and MF systems in reinforcement learning. Further, subjects did not remain at one level of MB/MF behaviour but rather displayed a shift towards more MB behavior over the first two blocks that was not attributable to the rate of contingency changes but rather to the extent of training. We demonstrate that flexibility to contingency changes can distinguish MB and MF strategies, with human subjects utilizing a hybrid strategy that shifts towards more MB behavior over blocks, consequently corresponding to a higher payoff.

  8. Optimization of Key Parameters of Energy Management Strategy for Hybrid Electric Vehicle Using DIRECT Algorithm

    Directory of Open Access Journals (Sweden)

    Jingxian Hao

    2016-11-01

    Full Text Available The rule-based logic threshold control strategy has been frequently used in energy management strategies for hybrid electric vehicles (HEVs owing to its convenience in adjusting parameters, real-time performance, stability, and robustness. However, the logic threshold control parameters cannot usually ensure the best vehicle performance at different driving cycles and conditions. For this reason, the optimization of key parameters is important to improve the fuel economy, dynamic performance, and drivability. In principle, this is a multiparameter nonlinear optimization problem. The logic threshold energy management strategy for an all-wheel-drive HEV is comprehensively analyzed and developed in this study. Seven key parameters to be optimized are extracted. The optimization model of key parameters is proposed from the perspective of fuel economy. The global optimization method, DIRECT algorithm, which has good real-time performance, low computational burden, rapid convergence, is selected to optimize the extracted key parameters globally. The results show that with the optimized parameters, the engine operates more at the high efficiency range resulting into a fuel savings of 7% compared with non-optimized parameters. The proposed method can provide guidance for calibrating the parameters of the vehicle energy management strategy from the perspective of fuel economy.

  9. Development of goods movement strategic transportation directions : Workshop on opportunities and strategies : final workshop report

    Energy Technology Data Exchange (ETDEWEB)

    Advokaat, E. [Lura Consulting, Toronto, ON (Canada)

    2003-04-01

    This paper presents a newly developed strategy for the movement of goods that will support economic development and competitiveness in Central Ontario. The strategy was developed at a workshop which examined current and emerging conditions that influence the movement of goods in Central Ontario along with the challenges and opportunities for goods movement. Possible short-term actions and long-term directions that can be incorporated into a strategy were also discussed. Attendees included representatives from all levels of government as well as shippers, trucking firms, rail, air and marine carriers, and port authorities. The study area included the Greater Toronto Area, Hamilton, the Regional Municipality of Niagara, the Regional Municipality of Waterloo and surrounding counties. It was recommended that any movement of goods strategy should consider population increases, land use planning, cross-border issues, the Kyoto Protocol, traffic issues, rail transport, e-commerce and market competition. The workshop also provided a forum to discuss coordination efforts, intergovernmental complexity, lack of funding, data gaps, marine transport, travel demand management, the problem with 'business-as-usual' scenarios, and inconsistent support from the province of Ontario. Participants expressed the need for an institution such as the Freight Council which is dedicated to issues regarding the movement of goods. The notion of expanding and maintaining a rail network was also supported by many participants.

  10. Recent progress in the direct synthesis of hierarchical zeolites: synthetic strategies and characterization methods

    KAUST Repository

    Liu, Zhaohui

    2017-06-16

    Hierarchically structured zeolites combine the merits of microporous zeolites and mesoporous materials to offer enhanced molecular diffusion and mass transfer without compromising the inherent catalytic activities and selectivity of zeolites. This short review gives an introduction to the synthesis strategies for hierarchically structured zeolites with emphasis on the latest progress in the route of ‘direct synthesis’ using various templates. Several characterization methods that allow us to evaluate the ‘quality’ of complex porous structures are also introduced. At the end of this review, an outlook is given to discuss some critical issues and challenges regarding the development of novel hierarchically structured zeolites as well as their applications.

  11. Surveillance indicators and their use in implementation of the Marine Strategy Framework Directive

    DEFF Research Database (Denmark)

    Shephard, Samuel; Greenstreet, Simon P. R.; Piet, GerJan J.

    2015-01-01

    The European Union Marine Strategy Framework Directive (MSFD) uses indicators to track ecosystem state in relation to Good Environmental Status (GES). These indicators were initially expected to be “operational”, i.e. to have well-understood relationships between state and specified anthropogenic...... pressure(s), and to have defined targets. Recent discussion on MSFD implementation has highlighted an additional class of “surveillance” indicators. Surveillance indicators monitor key aspects of the ecosystem for which there is: first, insufficient evidence to define targets and support formal state...

  12. Experimental evolution and the adjustment of metabolic strategies in lactic acid bacteria

    NARCIS (Netherlands)

    Bachmann, Herwig; Molenaar, Douwe; Branco dos Santos, Filipe; Teusink, Bas

    2017-01-01

    Experimental evolution of microbes has gained lots of interest in recent years, mainly due to the ease of strain characterisation through next-generation sequencing. While evolutionary and systems biologists use experimental evolution to address fundamental questions in their respective fields,

  13. Direct marketing of parenting programs: comparing a promotion-focused and a prevention-focused strategy.

    Science.gov (United States)

    Salari, Raziye; Backman, Anna

    2017-06-01

    : For parenting programs to achieve a public health impact, it is necessary to develop more effective marketing strategies to increase public awareness of these programs and promote parental participation. In this article, we compared a promotion-focused and a prevention-focused strategy via two studies. : We designed two ads inviting parents to participate in a universal parenting program; one ad focused on the program increasing the likelihood of positive outcomes for children (promotion-focused) and the other on the program reducing the likelihood of negative outcomes (prevention-focused). In study I, the two ads were run online simultaneously. Those who clicked on an ad were directed to a website where they could read about and sign up for the program. In study II, a community sample of 706 parents answered a questionnaire about the ads. : In study I, over 85 days, the prevention ad generated more clicks. There was no difference in the number of pages visited on the website nor in the number of parents who signed up for the program. In study II, parents showed a preference for the promotion ad, perceiving it as more relevant and rating it as more effective in getting them interested in the program. : A prevention strategy may be more effective in drawing public attention, in general. However, a promotion strategy is more likely to reach parents, in particular, and inspire them to consider participating in parenting programs. These strategies should be developed further and tested in both general and clinical populations. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  14. Direct benefits and the evolution of female-biased cooperative breeding in Seychelles warblers

    NARCIS (Netherlands)

    Richardson, David S.; Burke, Terry; Komdeur, Jan; Dunn, P.

    2002-01-01

    Inclusive fitness benefits have been suggested to be a major selective force behind the evolution of cooperative breeding. We investigated the fitness benefits selecting for cooperative breeding in the Seychelles warbler, Acroccphalus sechellensis. A microsatellite-based genotyping method was used

  15. Parameter Improved Particle Swarm Optimization Based Direct-Current Vector Control Strategy for Solar PV System

    Directory of Open Access Journals (Sweden)

    NAMMALVAR, P.

    2018-02-01

    Full Text Available This paper projects Parameter Improved Particle Swarm Optimization (PIPSO based direct current vector control technology for the integration of photovoltaic array in an AC micro-grid to enhance the system performance and stability. A photovoltaic system incorporated with AC micro-grid is taken as the pursuit of research study. The test system features two power converters namely, PV side converter which consists of DC-DC boost converter with Perturbation and Observe (P&O MPPT control to reap most extreme power from the PV array, and grid side converter which consists of Grid Side-Voltage Source Converter (GS-VSC with proposed direct current vector control strategy. The gain of the proposed controller is chosen from a set of three values obtained using apriori test and tuned through the PIPSO algorithm so that the Integral of Time multiplied Absolute Error (ITAE between the actual and the desired DC link capacitor voltage reaches a minimum and allows the system to extract maximum power from PV system, whereas the existing d-q control strategy is found to perform slowly to control the DC link voltage under varying solar insolation and load fluctuations. From simulation results, it is evident that the proposed optimal control technique provides robust control and improved efficiency.

  16. Evaluation of a Tailored Direct-Mail Marketing Strategy for Recruiting the 19- to 23-Year-Old Market.

    Science.gov (United States)

    1983-05-01

    17AD-A12.9 860 EVALUATION OF A TAILORED DIRECT-MAIL MARKETING STRATEGY 1/ FOR RECRUITNG TH.U) WESAT INC ROCKVILLE MD K FERNANDES ET AL MAY 83 NPRDC...STANDARDS-1963-A EVALUATION OF A TAILORED DIRECT-MAIL MARKETING STRATEGY FOR RECRUITING THE 19- TO 23-YEAR-OLD MARKET APPRVEDFORPUBLIC RELE AnE [B...EVALUATION OF A TAILORED DIRECT-MAIL MARKETING STRATEGY FOR RECRUITING THE 19- TO 23-YEAR-OLD MARKET Kathleen Fernandes Navy Personnel Research and

  17. Evaluation of the implementation of the directly observed treatment strategy for tuberculosis in a large city.

    Science.gov (United States)

    Lavôr, Débora Cristina Brasil da Silva; Pinheiro, Jair Dos Santos; Gonçalves, Maria Jacirema Ferreira

    2016-04-01

    To assess the degree of implementation of the Directly Observed Treatment, Short-course - DOTS for tuberculosis (TB) in a large city. Assessment of the implementation of the logic model, whose new cases of infectious pulmonary TB were recruited from specialized clinics and followed-up in basic health units. The judgment matrix covering the five components of the DOTS strategy were used. The result of the logic model indicates DOTS was partially implemented. In external, organizational and implementation contexts, the DOTS strategy was partially implemented; and, the effectiveness was not implemented. The partial implementation of the DOTS strategy in the city of Manaus did not reflect in TB control compliance, leading to low effectiveness of the program. Avaliar o grau de implantação da estratégia de tratamento diretamente observado (Directly Observed Treatment, Short-course - DOTS) para tuberculose (TB) em um município de grande porte. Avaliação de implantação por meio de modelo lógico, cujos casos novos de TB pulmonar bacilífera foram recrutados em ambulatórios especializados e acompanhados nas unidades básicas de saúde. Utilizou-se matriz de julgamento que abrange os cinco componentes da estratégia DOTS. O resultado do modelo lógico indica DOTS implantada parcialmente. Nos contextos externo, organizacional e de implantação, a estratégia DOTS está implantada parcialmente; e, na efetividade não está implantada. A implantação parcial da estratégia DOTS, na cidade de Manaus, reflete na não conformidade do controle da TB, levando à baixa efetividade do programa.

  18. Directed evolution of the periodic table: probing the electronic structure of late actinides.

    Science.gov (United States)

    Marsh, M L; Albrecht-Schmitt, T E

    2017-07-25

    Recent investigations of the coordination chemistry and physical properties of berkelium (Z = 97) and californium (Z = 98) have revealed fundamental differences between post-curium elements and lighter members of the actinide series. This review highlights these developments and chronicles key findings and concepts from the last half-century that have helped usher in a new understanding of the evolution of electronic structure in the periodic table.

  19. Direct Analysis as a historical documentation tool of the remains of the Castielfabib ramparts and their evolution (Valencian Community, Spain

    Directory of Open Access Journals (Sweden)

    Álvaro Vázquez Esparza

    2017-12-01

    Full Text Available   Castielfabib is a small town on the frontier between the old Spanish kingdoms of Castilla and Aragon. Due to the fact that the few remaining segments of its old walls are widely separated from each other, it is not possible to establish with any certainty a plan of the original ramparts. There is also the added complication of the wide variety of materials of which the different segments are composed, which makes it difficult to date or establish relationships between them. This meant that direct analysis of the masonry and paraments by digital tools was the only practical method of obtaining scientific data on the evolution of the different remains as a basis for forming sound hypotheses on their construction and evolution.

  20. Impact of weed control strategies on resistance evolution in Alopecurus myosuroides – a long-term field trial

    Directory of Open Access Journals (Sweden)

    Ulber, Lena

    2016-02-01

    Full Text Available The impact of various herbicide strategies on populations of Alopecurus myosuroides is investigated in a longterm field trial situated in Wendhausen (Germany since 2009. In the initial years of the field experiment, resistant populations were selected by means of repeated application of the same herbicide active ingredients. For the selection of different resistance profiles, herbicides with actives from different HRAC groups were used. The herbicide actives flupyrsulfuron, isoproturon und fenoxaprop-P were applied for two years on large plots. In a succeeding field trial starting in 2011, it was investigated if the now existing resistant field populations could be controlled by various herbicide strategies. Eight different strategies consisting of various herbicide combinations were tested. Resistance evolution was investigated by means of plant counts and molecular genetic analysis.

  1. Directed evolution of a β-mannanase from Rhizomucor miehei to improve catalytic activity in acidic and thermophilic conditions.

    Science.gov (United States)

    Li, Yan-Xiao; Yi, Ping; Yan, Qiao-Juan; Qin, Zhen; Liu, Xue-Qiang; Jiang, Zheng-Qiang

    2017-01-01

    β-Mannanase randomly cleaves the β-1,4-linked mannan backbone of hemicellulose, which plays the most important role in the enzymatic degradation of mannan. Although the industrial applications of β-mannanase have tremendously expanded in recent years, the wild-type β-mannanases are still defective for some industries. The glycoside hydrolase (GH) family 5 β-mannanase ( Rm Man5A) from Rhizomucor miehei shows many outstanding properties, such as high specific activity and hydrolysis property. However, owing to the low catalytic activity in acidic and thermophilic conditions, the application of Rm Man5A to the biorefinery of mannan biomasses is severely limited. To overcome the limitation, Rm Man5A was successfully engineered by directed evolution. Through two rounds of screening, a mutated β-mannanase (m Rm Man5A) with high catalytic activity in acidic and thermophilic conditions was obtained, and then characterized. The mutant displayed maximal activity at pH 4.5 and 65 °C, corresponding to acidic shift of 2.5 units in optimal pH and increase by 10 °C in optimal temperature. The catalytic efficiencies ( k cat / K m ) of m Rm Man5A towards many mannan substrates were enhanced more than threefold in acidic and thermophilic conditions. Meanwhile, the high specific activity and excellent hydrolysis property of Rm Man5A were inherited by the mutant m Rm Man5A after directed evolution. According to the result of sequence analysis, three amino acid residues were substituted in m Rm Man5A, namely Tyr233His, Lys264Met, and Asn343Ser. To identify the function of each substitution, four site-directed mutations (Tyr233His, Lys264Met, Asn343Ser, and Tyr233His/Lys264Met) were subsequently generated, and the substitutions at Tyr233 and Lys264 were found to be the main reason for the changes of m Rm Man5A. Through directed evolution of Rm Man5A, two key amino acid residues that controlled its catalytic efficiency under acidic and thermophilic conditions were identified

  2. Niche-driven evolution of metabolic and life-history strategies in natural and domesticated populations of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Sicard Delphine

    2009-12-01

    Full Text Available Abstract Background Variation of resource supply is one of the key factors that drive the evolution of life-history strategies, and hence the interactions between individuals. In the yeast Saccharomyces cerevisiae, two life-history strategies related to different resource utilization have been previously described in strains from different industrial origins. In this work, we analyzed metabolic traits and life-history strategies in a broader collection of yeast strains sampled in various ecological niches (forest, human body, fruits, laboratory and industrial environments. Results By analysing the genetic and plastic variation of six life-history and three metabolic traits, we showed that S. cerevisiae populations harbour different strategies depending on their ecological niches. On one hand, the forest and laboratory strains, referred to as extreme "ants", reproduce quickly, reach a large carrying capacity and a small cell size in fermentation, but have a low reproduction rate in respiration. On the other hand, the industrial strains, referred to as extreme "grasshoppers", reproduce slowly, reach a small carrying capacity but have a big cell size in fermentation and a high reproduction rate in respiration. "Grasshoppers" have usually higher glucose consumption rate than "ants", while they produce lower quantities of ethanol, suggesting that they store cell resources rather than secreting secondary products to cross-feed or poison competitors. The clinical and fruit strains are intermediate between these two groups. Conclusions Altogether, these results are consistent with a niche-driven evolution of S. cerevisiae, with phenotypic convergence of populations living in similar habitat. They also revealed that competition between strains having contrasted life-history strategies ("ants" and "grasshoppers" seems to occur at low frequency or be unstable since opposite life-history strategies appeared to be maintained in distinct ecological niches.

  3. Effects of Embedded and Direct Language Strategies on Prekindergarten Students' Cognitive and Social Emotional Development

    Science.gov (United States)

    Dominy, Matthew L.

    2012-01-01

    The purpose of this study is to measure the effect of a standard of care embedded language strategies program utilized in combination with direct language strategy instruction on the measured expressive language, cognitive development, social emotional development, and language development of prekindergarten students attending three neighborhood…

  4. Microplastics in seawater: Recommendations from the Marine Strategy Framework Directive implementation process

    Directory of Open Access Journals (Sweden)

    Jesus Gago

    2016-11-01

    Full Text Available Microplastic litter is a pervasive pollutant present in marine systems across the globe. The legacy of microplastics pollution in the marine environment today may remain for years to come due to the persistence of these materials. Microplastics are emerging contaminants of potential concern and as yet there are few recognised approaches for monitoring. In 2008, the EU Marine Strategy Framework Directive (MSFD, 2008/56/EC included microplastics as an aspect to be measured. Here we outline the approach as discussed by the European Union expert group on marine litter, the technical Subgroup on Marine litter (TSG-ML, with a focus on the implementation of monitoring microplastics in seawater in European seas. It is concluded that harmonization and coherence is needed to achieve reliable monitoring.

  5. Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

    Science.gov (United States)

    Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

    2018-05-01

    NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

  6. A Practical Teaching Course in Directed Protein Evolution Using the Green Fluorescent Protein as a Model

    Science.gov (United States)

    Ruller, Roberto; Silva-Rocha, Rafael; Silva, Artur; Schneider, Maria Paula Cruz; Ward, Richard John

    2011-01-01

    Protein engineering is a powerful tool, which correlates protein structure with specific functions, both in applied biotechnology and in basic research. Here, we present a practical teaching course for engineering the green fluorescent protein (GFP) from "Aequorea victoria" by a random mutagenesis strategy using error-prone polymerase…

  7. Co-evolution of Industry Strategies and Government Policies: The Case of the Brazilian Automotive Industry

    Directory of Open Access Journals (Sweden)

    Roberto Gonzalez Duarte

    2017-07-01

    Full Text Available This study examines the evolution of the automotive industry in Brazil and its key drivers. We argue that the rules of the game – industry policies – are an outcome of exchanges between the host government and industry. These arise from changes in economic and political environments and interdependence between industry and the country’s economy. To this end, we draw upon literature on institutions and co-evolution to understand the industry footprint over a 50-year period, as well as its relationship with changes in government policies. This study generates new insights on institutional and co-evolution political perspectives by showing that the rules of the game are not only the making of the government, but are also the result of interdependencies between industry and government.

  8. Routing Protocols for Underwater Wireless Sensor Networks: Taxonomy, Research Challenges, Routing Strategies and Future Directions.

    Science.gov (United States)

    Khan, Anwar; Ali, Ihsan; Ghani, Abdullah; Khan, Nawsher; Alsaqer, Mohammed; Rahman, Atiq Ur; Mahmood, Hasan

    2018-05-18

    Recent research in underwater wireless sensor networks (UWSNs) has gained the attention of researchers in academia and industry for a number of applications. They include disaster and earthquake prediction, water quality and environment monitoring, leakage and mine detection, military surveillance and underwater navigation. However, the aquatic medium is associated with a number of limitations and challenges: long multipath delay, high interference and noise, harsh environment, low bandwidth and limited battery life of the sensor nodes. These challenges demand research techniques and strategies to be overcome in an efficient and effective fashion. The design of routing protocols for UWSNs is one of the promising solutions to cope with these challenges. This paper presents a survey of the routing protocols for UWSNs. For the ease of description, the addressed routing protocols are classified into two groups: localization-based and localization-free protocols. These groups are further subdivided according to the problems they address or the major parameters they consider during routing. Unlike the existing surveys, this survey considers only the latest and state-of-the-art routing protocols. In addition, every protocol is described in terms of its routing strategy and the problem it addresses and solves. The merit(s) of each protocol is (are) highlighted along with the cost. A description of the protocols in this fashion has a number of advantages for researchers, as compared to the existing surveys. Firstly, the description of the routing strategy of each protocol makes its routing operation easily understandable. Secondly, the demerit(s) of a protocol provides (provide) insight into overcoming its flaw(s) in future investigation. This, in turn, leads to the foundation of new protocols that are more intelligent, robust and efficient with respect to the desired parameters. Thirdly, a protocol can be selected for the appropriate application based on its described

  9. Main-chain-directed strategy for the assignment of 1H NMR spectra of proteins

    International Nuclear Information System (INIS)

    Englander, S.W.; Wand, A.J.

    1987-01-01

    A strategy for assigning the resonances in two-dimensional (2D) NMR spectra of proteins is described. The method emphasizes the analysis of through-space relationships between protons by use of the two-dimensional nuclear Overhauser effect (NOE) experiment. NOE patterns used in the algorithm were derived from a statistical analysis of the combinations of short proton-proton distances observed in the high-resolution crystal structures of 21 proteins. One starts with a search for authentic main-chain NH-C/sub α/H-C/sub β/H J-coupled units, which can be found with high reliability. The many main-chain units of a protein are then placed in their proper juxtaposition by recognition of predefined NOE connectivity patterns. To discover these connectivities, the 2D NOE spectrum is examined, in a prescribed order, for the distinct NOE patterns characteristic of helices, sheets, turns, and extended chain. Finally, the recognition of a few amino acid side-chain types places the discovered secondary structure elements within the polypeptide sequences. Unlike the sequential assignment approach, the main-chain-directed strategy does not rely on the difficult task of recognizing many side-chain spin systems in J-correlated spectra, the assignment process is not in general sequential with the polypeptide chain, and the prescribed connectivity patterns are cyclic rather than linear. The latter characteristic avoids ambiguous branch points in the analysis and imposed an internally confirmatory property on each forward step

  10. Library Learning: Undergraduate Students’ Informal, Self-directed, and Information Sharing Strategies

    Directory of Open Access Journals (Sweden)

    Jo Ann Murphy

    2014-04-01

    Full Text Available A focus group study of fourteen University of Saskatchewan second to fourth year humanities and social science undergraduate students was conducted in the fall of 2011. The purpose of the research was to determine how students learn about library resources and services. Findings indicate that the participants often use a variety of informal, self-directed and information sharing strategies. Seeking help from professors, peers, friends, and family members is a common practice. Convenience, familiarity, and perceived knowledge are key factors that determine who and how these students learn about the library. Formal instruction and seeking assistance from librarians did not resonate for participants as a typical approach for learning about the library. The author suggests that undergraduate students engage in informal learning and information sharing as many ‘adult learners’ do, similar to an employment setting. The library, within the formal educational structure, lends itself to a more informal learning context. The study concludes that libraries must continue to develop resources, services, and innovative programs that support students’ informal learning styles, while also providing formal instruction as part of the undergraduate curriculum ensuring students are exposed early on to core foundational skills that contribute to their success as informal and self-directed learners.

  11. The implementation of the EU renewable directive in Spain. Strategies and challenges

    International Nuclear Information System (INIS)

    Labriet, Maryse; Cabal, Helena; Lechon, Yolanda; Giannakidis, George; Kanudia, Amit

    2010-01-01

    Based on the European project RES2020, the analysis evaluates the energy strategies to be implemented in Spain in order to satisfy the EU Renewable Directive. The modelling framework relies on the technico-economic model TIMES-Spain, part of the Pan-European TIMES model used in the project. TIMES is a bottom-up technology rich optimisation model representing the whole energy systems of the countries. Among the results, it appears that the gap regarding the renewable deployment in Spain between the Business-as-Usual case (including the existing policies) and the EU Directive should be compensated mainly by the penetration of bioenergy in transport and industry, and by the implementation of conservation measures, which contribute to reduce the total energy demand and thus makes useless additional investments in renewable power plants compared to the Business-as-Usual case. Only higher climate mitigation ambitions result in an absolute increase in the renewable-based electricity generation compared to the Business-as-Usual case. Moreover, when allowed, Spain is offering renewable energy credits under the statistical transfer mechanism to other European countries. The cost increase of the modelled renewable and climate policies compared to the Business-as-Usual remains relatively minor.

  12. Using direct-to-consumer marketing strategies with obsessive-compulsive disorder in the nonprofit sector.

    Science.gov (United States)

    Szymanski, Jeff

    2012-06-01

    Three to four million individuals struggle with obsessive-compulsive disorder (OCD) in the United States at any given time. OCD can be a debilitating disorder associated with significant quality-of-life and occupational impairment. First-line treatments for OCD (selective serotonin reuptake inhibitors and exposure and response prevention therapy) have been shown to be effective; yet, many individuals suffering from OCD experience multiple barriers to accessing these treatments. In fact, it can take as many as 17 years from onset of symptoms to effective treatment. Given the need to increase access to and utilization of effective treatments, direct-to-consumer marketing in the context of OCD appears crucial. The International OCD Foundation (formerly the Obsessive Compulsive Foundation) was established as a nonprofit organization with a mission to educate the public and mental health professionals about appropriate practice guidelines, raise awareness of the disorder, and ensure that individuals looking for treatment find the necessary resources. This paper reviews the obstacles those struggling with OCD face in their attempts to alleviate suffering, as well as the direct-to-consumer strategies and tactics used by the International OCD Foundation to improve access to empirically supported, effective treatment. Copyright © 2011. Published by Elsevier Ltd.

  13. Novel Naphthalene Based Lariat-Type Crown Ethers Using Direct Single Electron Transfer Photochemical Strategy

    International Nuclear Information System (INIS)

    Park, Hea Jung; Sung, Nam Kyung; Kim, Su Rhan; Kim, Su Rhan; Ahn, So Hyun; Yoon, Ung Chan; Cho, Dae Won; Mariano, Patrick S.

    2013-01-01

    This study explored a direct SET-photochemical strategy to construct a new family of thioene conjugated-naphthalamide fluorophore based lariat-crown ethers which show strong binding properties towards heavy metal ions. Irradiations of designed nitrogen branched (trimethylsilyl)methylthio-terminated polyethylenoxy-tethered naphthalimides in acidic methanol solutions have led to highly efficient photocyclization reactions to generate naphthalamide based lariat type thiadiazacrown ethers directly in chemo- and regio-selective manners which undergo very facile secondary dehydration reactions during separation processes to produce their corresponding amidoenethio ether cyclic products tethered with electron donating diethyleneoxy- and diethyenethio-side arm chains. Fluorescence and metal cation binding properties of the lariat type enamidothio products were examined. The photocyclized amidoenethio products, thioene conjugated naphthalamide fluorophore containing lariat-thiadiazacrowns exhibited strong fluorescence emissions in region of 330-450 nm along with intramolecular exciplex emissions in region of 450-560 nm with their maxima at 508 nm. Divalent cation Hg 2+ and Pb 2+ showed strong binding to sulfur atom(s) in side arm chain and atoms in enethiadiazacrown ether rings which led to significant enhancement of fluorescence from its chromophore singlet excited state and concomitant quenching of exciplex emission. The dual fluorescence emission responses towards divalent cations might provide a new guide for design and development of fluorescence sensors for detecting those metals

  14. Novel Naphthalene Based Lariat-Type Crown Ethers Using Direct Single Electron Transfer Photochemical Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hea Jung; Sung, Nam Kyung; Kim, Su Rhan; Kim, Su Rhan; Ahn, So Hyun; Yoon, Ung Chan [Pusan National Univ., Busan (Korea, Republic of); Cho, Dae Won [Yeungnam Univ., Geoungsan (Korea, Republic of); Mariano, Patrick S. [Univ. of New Mexico, Albuquerque (United States)

    2013-12-15

    This study explored a direct SET-photochemical strategy to construct a new family of thioene conjugated-naphthalamide fluorophore based lariat-crown ethers which show strong binding properties towards heavy metal ions. Irradiations of designed nitrogen branched (trimethylsilyl)methylthio-terminated polyethylenoxy-tethered naphthalimides in acidic methanol solutions have led to highly efficient photocyclization reactions to generate naphthalamide based lariat type thiadiazacrown ethers directly in chemo- and regio-selective manners which undergo very facile secondary dehydration reactions during separation processes to produce their corresponding amidoenethio ether cyclic products tethered with electron donating diethyleneoxy- and diethyenethio-side arm chains. Fluorescence and metal cation binding properties of the lariat type enamidothio products were examined. The photocyclized amidoenethio products, thioene conjugated naphthalamide fluorophore containing lariat-thiadiazacrowns exhibited strong fluorescence emissions in region of 330-450 nm along with intramolecular exciplex emissions in region of 450-560 nm with their maxima at 508 nm. Divalent cation Hg{sup 2+} and Pb{sup 2+} showed strong binding to sulfur atom(s) in side arm chain and atoms in enethiadiazacrown ether rings which led to significant enhancement of fluorescence from its chromophore singlet excited state and concomitant quenching of exciplex emission. The dual fluorescence emission responses towards divalent cations might provide a new guide for design and development of fluorescence sensors for detecting those metals.

  15. Strategies for specifically directing metal functionalization of protein nanotubes: constructing protein coated silver nanowires

    International Nuclear Information System (INIS)

    Carreño-Fuentes, Liliana; Palomares, Laura A; Ramírez, Octavio T; Ascencio, Jorge A; Medina, Ariosto; Aguila, Sergio

    2013-01-01

    Biological molecules that self-assemble in the nanoscale range are useful multifunctional materials. Rotavirus VP6 protein self-assembles into tubular structures in the absence of other rotavirus proteins. Here, we present strategies for selectively directing metal functionalization to the lumen of VP6 nanotubes. The specific in situ metal reduction in the inner surface of nanotube walls was achieved by the simple modification of a method previously reported to functionalize the nanotube outer surface. Silver nanorods and nanowires as long as 1.5 μm were formed inside the nanotubes by coalescence of nanoparticles. Such one-dimensional structures were longer than others previously obtained using bioscaffolds. The interactions between silver ions and the nanotube were simulated to understand the conditions that allowed nanowire formation. Molecular docking showed that a naturally occurring arrangement of aspartate residues enabled the stabilization of silver ions on the internal surface of the VP6 nanotubes. This is the first time that such a spatial arrangement has been proposed for the nucleation of silver nanoparticles, opening the possibility of using such an array to direct functionalization of other biomolecules. These results demonstrate the natural capabilities of VP6 nanotubes to function as a versatile biotemplate for nanomaterials. (paper)

  16. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Science.gov (United States)

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  17. A Video Game for Learning Brain Evolution: A Resource or a Strategy?

    Science.gov (United States)

    Barbosa Gomez, Luisa Fernanda; Bohorquez Sotelo, Maria Cristina; Roja Higuera, Naydu Shirley; Rodriguez Mendoza, Brigitte Julieth

    2016-01-01

    Learning resources are part of the educational process of students. However, how video games act as learning resources in a population that has not selected the virtual formation as their main methodology? The aim of this study was to identify the influence of a video game in the learning process of brain evolution. For this purpose, the opinions…

  18. Co-evolution of industry strategies and government policies: The case of the brazilian automotive industry

    NARCIS (Netherlands)

    Duarte, R.G. (Roberto Gonzalez); S.B. Rodrigues (Suzana)

    2017-01-01

    textabstractThis study examines the evolution of the automotive industry in Brazil and its key drivers. We argue that the rules of the game – industry policies – are an outcome of exchanges between the host government and industry. These arise from changes in economic and political environments and

  19. Evolution of Learning among Pavlov Strategies in a Competitive Environment with Noise.

    Science.gov (United States)

    Kraines, David; Kraines, Vivian

    1995-01-01

    Pavlov denotes a family of stochastic learning strategies that achieves the mutually cooperative outcome in the iterated prisoner's dilemma against a wide variety of strategies. Although faster learners will eventually dominate a given homogeneous Pavlov population, the process must proceed through a gradual increase in the rate of learning. (JBJ)

  20. Changes in motor unit recruitment strategy during pain alters force direction.

    Science.gov (United States)

    Tucker, Kylie J; Hodges, Paul W

    2010-10-01

    Motor unit (MU) recruitment is altered (decreased discharge rate and cessation of discharge in some units, and recruitment of new units) in force-matched contractions during pain compared to contractions performed before pain. As MU's within a motoneurone pool have different force direction properties we hypothesised that altered MU recruitment during experimental knee pain would change the force vector (total force (F(T)): amplitude and angle) generated by the quadriceps. Force was produced at two levels during 1 × 60-s and 3 × 10-s isometric contractions of knee extensors, and recorded by two force transducers at right angles. This enabled calculation of both F(E) (extension force) and F(T). MU recruitment was recorded from the medial and lateral vastii with four fine-wire electrodes. Pain was induced by hypertonic saline injection in the infra-patella fat pad. Nine subjects matched F(E) and six subjects also matched both medial and lateral forces (F(T)) before and during pain. Changes in MU discharge pattern (decreased discharge rate (Precruitment of new units) during pain were associated with a ∼5° change in absolute force angle. As force angle changed in both directions (left/right) for individual subjects with pain there was no change in average F(T) amplitude between conditions. When both medial and lateral forces were matched MU discharge rate decreased (Punits ceased firing or were newly recruited during pain. Change in motoneurone recruitment during pain alters direction of muscle force. This may be a strategy to avoid pain or protect the painful part. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  1. Directed divergent evolution of a thermostable D-tagatose epimerase towards improved activity for two hexose substrates.

    Science.gov (United States)

    Bosshart, Andreas; Hee, Chee Seng; Bechtold, Matthias; Schirmer, Tilman; Panke, Sven

    2015-03-02

    Functional promiscuity of enzymes can often be harnessed as the starting point for the directed evolution of novel biocatalysts. Here we describe the divergent morphing of an engineered thermostable variant (Var8) of a promiscuous D-tagatose epimerase (DTE) into two efficient catalysts for the C3 epimerization of D-fructose to D-psicose and of L-sorbose to L-tagatose. Iterative single-site randomization and screening of 48 residues in the first and second shells around the substrate-binding site of Var8 yielded the eight-site mutant IDF8 (ninefold improved kcat for the epimerization of D-fructose) and the six-site mutant ILS6 (14-fold improved epimerization of L-sorbose), compared to Var8. Structure analysis of IDF8 revealed a charged patch at the entrance of its active site; this presumably facilitates entry of the polar substrate. The improvement in catalytic activity of variant ILS6 is thought to relate to subtle changes in the hydration of the bound substrate. The structures can now be used to select additional sites for further directed evolution of the ketohexose epimerase. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Host-directed strategies using lipid nanoparticles to reduce mycobacteria survival

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L. [Faculty of Sciences and Technology of the New University of Lisbon (Portugal); Diogo, J.; Mateus, R.; Pimentel, M.; Videira, M., E-mail: mvideira@ff.ul.pt [iMed.UL - Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy of the University of Lisbon, Intracellular Trafficking Modulation for Advanced Drug Delivery InTraCell-ADD Research Group (Portugal)

    2015-02-15

    Antibiotic-resistant infections and the stagnations in the development of new drugs have increased the demand for new therapeutic approaches against Mycobacterium tuberculosis. Innovative systems that are able to target and eradicate the bacteria in the infected host cells may represent a therapeutic breakthrough while avoiding latency. The development of nanosystems aiming a controlled and targeted intracellular drug release, have proved to increase cytosolic therapeutic concentration while reducing undesired side effects. This work’s main goal was to develop a host-directed strategy against mycobacterial infection through the design of a biocompatible nanocarrier for phage-derived protein delivery, using M. smegmatis as model. Since mycobacterial pathogenicity is strongly supported by the presence of lipids in the cell wall, their degradation induces bacterial destruction through cell wall hydrolysis. Phage-based lipolytic enzymes such as, LysB a mycolylarabinogalactan esterase, represent an appealing therapeutic approach. The herein proposed Ms6 LysB-containing lipid nanocarrier (SLN-LysB) explores the known advantages of nanomedicine-based systems for phagocytic cells selectively targeting thus allowing LysB intracellular accumulation and a more pronounced mycobacterial infection eradication. Adsorption efficiency value indicates the potential of this system as a protein nanocarrier. Moreover, promising outcomes were obtained in host-infected macrophages treated with SLN-LysB. The results show that the herein proposed strategy was more effective in inhibiting the growth of M. smegmatis than free LysB, which might be related to the nanocarrier internalization. Acting as effective protein nanocarriers, the protein-guided delivery in the infected phagocytic cells allows it to exert its hydrolytic action on the lipid layer of the Mycobacterium.

  3. Host-directed strategies using lipid nanoparticles to reduce mycobacteria survival

    Science.gov (United States)

    Pereira, L.; Diogo, J.; Mateus, R.; Pimentel, M.; Videira, M.

    2015-02-01

    Antibiotic-resistant infections and the stagnations in the development of new drugs have increased the demand for new therapeutic approaches against Mycobacterium tuberculosis. Innovative systems that are able to target and eradicate the bacteria in the infected host cells may represent a therapeutic breakthrough while avoiding latency. The development of nanosystems aiming a controlled and targeted intracellular drug release, have proved to increase cytosolic therapeutic concentration while reducing undesired side effects. This work's main goal was to develop a host-directed strategy against mycobacterial infection through the design of a biocompatible nanocarrier for phage-derived protein delivery, using M. smegmatis as model. Since mycobacterial pathogenicity is strongly supported by the presence of lipids in the cell wall, their degradation induces bacterial destruction through cell wall hydrolysis. Phage-based lipolytic enzymes such as, LysB a mycolylarabinogalactan esterase, represent an appealing therapeutic approach. The herein proposed Ms6 LysB-containing lipid nanocarrier (SLN_LysB) explores the known advantages of nanomedicine-based systems for phagocytic cells selectively targeting thus allowing LysB intracellular accumulation and a more pronounced mycobacterial infection eradication. Adsorption efficiency value indicates the potential of this system as a protein nanocarrier. Moreover, promising outcomes were obtained in host-infected macrophages treated with SLN_LysB. The results show that the herein proposed strategy was more effective in inhibiting the growth of M. smegmatis than free LysB, which might be related to the nanocarrier internalization. Acting as effective protein nanocarriers, the protein-guided delivery in the infected phagocytic cells allows it to exert its hydrolytic action on the lipid layer of the Mycobacterium.

  4. Host-directed strategies using lipid nanoparticles to reduce mycobacteria survival

    International Nuclear Information System (INIS)

    Pereira, L.; Diogo, J.; Mateus, R.; Pimentel, M.; Videira, M.

    2015-01-01

    Antibiotic-resistant infections and the stagnations in the development of new drugs have increased the demand for new therapeutic approaches against Mycobacterium tuberculosis. Innovative systems that are able to target and eradicate the bacteria in the infected host cells may represent a therapeutic breakthrough while avoiding latency. The development of nanosystems aiming a controlled and targeted intracellular drug release, have proved to increase cytosolic therapeutic concentration while reducing undesired side effects. This work’s main goal was to develop a host-directed strategy against mycobacterial infection through the design of a biocompatible nanocarrier for phage-derived protein delivery, using M. smegmatis as model. Since mycobacterial pathogenicity is strongly supported by the presence of lipids in the cell wall, their degradation induces bacterial destruction through cell wall hydrolysis. Phage-based lipolytic enzymes such as, LysB a mycolylarabinogalactan esterase, represent an appealing therapeutic approach. The herein proposed Ms6 LysB-containing lipid nanocarrier (SLN-LysB) explores the known advantages of nanomedicine-based systems for phagocytic cells selectively targeting thus allowing LysB intracellular accumulation and a more pronounced mycobacterial infection eradication. Adsorption efficiency value indicates the potential of this system as a protein nanocarrier. Moreover, promising outcomes were obtained in host-infected macrophages treated with SLN-LysB. The results show that the herein proposed strategy was more effective in inhibiting the growth of M. smegmatis than free LysB, which might be related to the nanocarrier internalization. Acting as effective protein nanocarriers, the protein-guided delivery in the infected phagocytic cells allows it to exert its hydrolytic action on the lipid layer of the Mycobacterium

  5. The Evolution of Airpower Theory and Future Air Strategies for Employment in the Gap

    National Research Council Canada - National Science Library

    Brown, Francis M

    2005-01-01

    .... In regards to future military involvement and specifically the application of airpower, what are the best air strategies to pursue, not only to achieve the strategic objectives, but to facilitate...

  6. An in vivo system for directed experimental evolution of rabbit haemorrhagic disease virus.

    Science.gov (United States)

    Hall, Robyn N; Capucci, Lorenzo; Matthaei, Markus; Esposito, Simona; Kerr, Peter J; Frese, Michael; Strive, Tanja

    2017-01-01

    The calicivirus Rabbit haemorrhagic disease virus (RHDV) is widely used in Australia as a biocontrol agent to manage wild European rabbit (Oryctolagus cuniculus) populations. However, widespread herd immunity limits the effectiveness of the currently used strain, CAPM V-351. To overcome this, we developed an experimental platform for the selection and characterisation of novel RHDV strains. As RHDV does not replicate in cell culture, variant viruses were selected by serially passaging a highly virulent RHDV field isolate in immunologically naïve laboratory rabbits that were passively immunised 18-24 hours post-challenge with a neutralising monoclonal antibody. After seven passages, two amino acid substitutions in the P2 domain of the capsid protein became fixed within the virus population. Furthermore, a synonymous substitution within the coding sequence of the viral polymerase appeared and was also maintained in all subsequent passages. These findings demonstrate proof-of-concept that RHDV evolution can be experimentally manipulated to select for virus variants with altered phenotypes, in this case partial immune escape.

  7. Metabolic Recruitment and Directed Evolution of Nucleoside Triphosphate Uptake in Escherichia coli.

    Science.gov (United States)

    Pezo, Valérie; Hassan, Camille; Louis, Dominique; Sargueil, Bruno; Herdewijn, Piet; Marlière, Philippe

    2018-05-18

    We report the design and elaboration of a selection protocol for importing a canonical substrate of DNA polymerase, thymidine triphosphate (dTTP) in Escherichia coli. Bacterial strains whose growth depend on dTTP uptake, through the action of an algal plastid transporter expressed from a synthetic gene inserted in the chromosome, were constructed and shown to withstand the simultaneous loss of thymidylate synthase and thymidine kinase. Such thyA tdk dual deletant strains provide an experimental model of tight nutritional containment for preventing dissemination of microbial GMOs. Our strains transported the four canonical dNTPs, in the following order of preference: dCTP > dATP ≥ dGTP > dTTP. Prolonged cultivation under limitation of exogenous dTTP led to the enhancement of dNTP transport by adaptive evolution. We investigated the uptake of dCTP analogues with altered sugar or nucleobase moieties, which were found to cause a loss of cell viability and an increase of mutant frequency, respectively. E. coli strains equipped with nucleoside triphosphate transporters should be instrumental for evolving organisms whose DNA genome is morphed chemically by fully substituting its canonical nucleotide components.

  8. Directed evolution improves the fibrinolytic activity of nattokinase from Bacillus natto.

    Science.gov (United States)

    Yongjun, Cai; Wei, Bao; Shujun, Jiang; Meizhi, Weng; Yan, Jia; Yan, Yin; Zhongliang, Zheng; Goulin, Zou

    2011-12-01

    Nattokinase (subtilisin NAT, NK) is a relatively effective microbial fibrinolytic enzyme that has been identified and characterized from Bacillus natto. In the current report, DNA family shuffling was used to improve the fibrinolytic activity of nattokinase. Three homologous genes from B. natto AS 1.107, Bacillus amyloliquefaciens CICC 20164 and Bacillus licheniformis CICC 10092 were shuffled to generate a mutant library. A plate-based method was used to screen the mutant libraries for improved activity. After three rounds of DNA shuffling, one desirable mutant with 16 amino acid substitutions was obtained. The mutant enzyme was purified and characterized. The kinetic measurements showed that the catalytic efficiency of the mutant NK was approximately 2.3 times higher than that of the wild-type nattokinase. In addition, the molecular modeling analysis suggested that the mutations affect the enzymatic function by changing the surface conformation of the substrate-binding pocket. The current study shows that the evolution of nattokinase with improved fibrinolytic activity by DNA family shuffling is feasible and provides useful references to facilitate the application of nattokinase in thrombolytic therapy. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  9. Evolution in nuclear strategy in US and Russia and its implications in arms control

    Energy Technology Data Exchange (ETDEWEB)

    Sokov, N

    2003-07-01

    Today, there is a growing tendency in war-fighting scenarios to include limited use of nuclear weapons. New developments in nuclear policy could be attributed to changes in the international situation like the multiplication of low level conflicts and the threat of terrorism. This paper analyzes the evolution of the Russian nuclear doctrine, the transformation of the US nuclear policy and their consequences on arms control. (J.S.)

  10. Pricing Strategy and the Formation and Evolution of Reference Price Perceptions in New Product Categories

    OpenAIRE

    Lowe, Ben; Alpert, Frank

    2010-01-01

    This study examines the formation and evolution of reference price perceptions in new product categories. It contributes to our understanding of pricing new products by integrating two important research streams in marketing-reference price theory and the theory of pioneer brand advantage. Prior research has focused solely on products in existing or incrementally new categories, and has typically examined fast-moving consumer goods. Using a cross-sectional experiment to study the formation of...

  11. Evolution in nuclear strategy in US and Russia and its implications in arms control

    International Nuclear Information System (INIS)

    Sokov, N.

    2003-01-01

    Today, there is a growing tendency in war-fighting scenarios to include limited use of nuclear weapons. New developments in nuclear policy could be attributed to changes in the international situation like the multiplication of low level conflicts and the threat of terrorism. This paper analyzes the evolution of the Russian nuclear doctrine, the transformation of the US nuclear policy and their consequences on arms control. (J.S.)

  12. Evolution Of The Operational Energy Strategy And Its Consideration In The Defense Acquisition Process

    Science.gov (United States)

    2016-09-01

    Figure 12. PPBE Process Flowchart . Source: AcqNotes (2016). We comment above that once a program manager has completed his major Defense...acquisition system: 1) acquisition, 2) requirements and 3) planning, programming , budgeting, and execution (PPBE). We looked at the evolution of...to gain traction or improve promulgation of key guidance and documentation for new-starts and/or upgrades to weapon system acquisition programs

  13. Temperature and direction dependence of internal strain and texture evolution during deformation of uranium

    Energy Technology Data Exchange (ETDEWEB)

    Brown, D.W., E-mail: dbrown@lanl.gov [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Bourke, M.A.M.; Clausen, B.; Korzekwa, D.R.; Korzekwa, R.C.; McCabe, R.J.; Sisneros, T.A.; Teter, D.F. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2009-06-25

    Depleted uranium is of current programmatic interest at Los Alamos National Lab due to its high density and nuclear applications. At room temperature, depleted uranium displays an orthorhombic crystal structure with highly anisotropic mechanical and thermal properties. For instance, the coefficient of thermal expansion is roughly 20 x 10{sup -6} deg. C{sup -1} in the a and c directions, but near zero or slightly negative in the b direction. The innate anisotropy combined with thermo-mechanical processing during manufacture results in spatially varying residual stresses and crystallographic texture, which can cause distortion, and failure in completed parts, effectively wasting resources. This paper focuses on the development of residual stresses and textures during deformation at room and elevated temperatures with an eye on the future development of computational polycrystalline plasticity models based on the known micro-mechanical deformation mechanisms of the material.

  14. The space-time evolution of an electrical discharge directed by a laser spark

    International Nuclear Information System (INIS)

    Asinovskii, E.I.; Vasilyak, L.M.; Unkovskii, S.Yu.

    1992-01-01

    The study of electrical discharges directed by a laser spark has been made necessary by the creation of new types of switches, plasma antennas, and lightning rods, channels for the transport of charged particle beams in inertial thermonuclear fusion devices, and also for modeling the processes in streak lightning. For the most part, previous studies have explored the feasibility of creating such discharges, depending on experimental conditions, and proposed possible mechanisms for the development of discharges, e.g., the stepwise nature of its propagation. A model was proposed in which the discharge front propagates as an ionization wave. This model was based on measurements of the electric potential along the trajectory of a directed discharge. To construct a model and obtain directed discharges with prescribed parameters, one must know the mechanisms of discharge development. In this work, the authors report the results of an electrooptical study of the origin and motion of luminous fronts of ionization waves in an electrical discharge during its initiation, both for a single breakdown site and for a long laser spark with a large number of laser breakdown sites. Results are presented of our study of the stability of a discharge for a current flow of long duration

  15. Particularities Regarding the Evolution and Role of Foreign Direct Investments in Romania’s Economy

    Directory of Open Access Journals (Sweden)

    Ion Botescu

    2016-01-01

    Full Text Available Criticized by some, praised by others foreign direct investments are a financial flow with amajor impact on the economies of many countries. In an increasingly globalized world, the processthrough which multinationals open production and distribution branches over the entire surface ofthe globe is something as natural as possible. After the fall of communism in Europe, Romania has been a favorite destination for manyforeign investors, fact which requires a careful analysis on the dynamics and structure of foreigndirect investment flows attracted by Romania. I have also tried to highlight the nature of the linkbetween the flow of foreign direct investment attracted by Romania and the variations recorded inthe economic development of our country. Given all the positive and negative aspects presented, foreign direct investments are a realityfor Romania, and future policies promoted in the area should stimulate the entry foreign capitalfirms whose work will generate a high level of content of knowledge and technology directlyimpacting the improvement of the economic efficiency at national level.

  16. Directional selection can drive the evolution of modularity in complex traits.

    Science.gov (United States)

    Melo, Diogo; Marroig, Gabriel

    2015-01-13

    Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

  17. The RNA-world and co-evolution hypotheses and the origin of life: Implications, research strategies and perspectives

    Science.gov (United States)

    Lahav, Noam

    1993-12-01

    The applicability of the RNA-world and co-evolution hypotheses to the study of the very first stages of the origin of life is discussed. The discussion focuses on the basic differences between the two hypotheses and their implications, with regard to the reconstruction methodology, ribosome emergence, balance between ribozymes and protein enzymes, and their major difficulties. Additional complexities of the two hypotheses, such as membranes and the energy source of the first reactions, are not treated in the present work. A central element in the proposed experimental strategies is the study of the catalytic activities of very small peptides and RNA-like oligomers, according to existing, as well as to yet-to-be-invented scenarios of the two hypotheses under consideration. It is suggested that the noveldirected molecular evolution technology, andmolecular computational modeling, can be applied to this research. This strategy is assumed to be essential for the suggested goal of future studies of the origin of life, namely, the establishment of a ‘Primordial Darwinian entity’.

  18. Adaptive co-evolution of strategies and network leading to optimal cooperation level in spatial prisoner's dilemma game

    International Nuclear Information System (INIS)

    Han-Shuang, Chen; Zhong-Huai, Hou; Hou-Wen, Xin; Ji-Qian, Zhang

    2010-01-01

    We study evolutionary prisoner's dilemma game on adaptive networks where a population of players co-evolves with their interaction networks. During the co-evolution process, interacted players with opposite strategies either rewire the link between them with probability p or update their strategies with probability 1 – p depending on their payoffs. Numerical simulation shows that the final network is either split into some disconnected communities whose players share the same strategy within each community or forms a single connected network in which all nodes are in the same strategy. Interestingly, the density of cooperators in the final state can be maximised in an intermediate range of p via the competition between time scale of the network dynamics and that of the node dynamics. Finally, the mean-field analysis helps to understand the results of numerical simulation. Our results may provide some insight into understanding the emergence of cooperation in the real situation where the individuals' behaviour and their relationship adaptively co-evolve. (general)

  19. Shopping for food with children: A strategy for directing their choices toward novel foods containing vegetables.

    Science.gov (United States)

    Allirot, Xavier; Maiz, Edurne; Urdaneta, Elena

    2018-01-01

    Involving children in the different steps of meal preparation has been suggested as a strategy for enhancing dietary habits in childhood. It has previously been shown that involving children in cooking can increase their willingness to taste novel foods and direct their food choices towards foods containing vegetables. The objective of the present study was to assess the effect of involving children in food purchasing on food choices, intake, liking and appetite. A between-subject experiment was conducted with 86 children (from 8 to 10 years old). Forty-three children (PURCHASE group) participated in a workshop dedicated to purchasing the necessary ingredients online for the preparation of three unfamiliar foods containing vegetables: apple and beetroot juice, zucchini tortilla sandwich and spinach cookies. Forty-three children (CONTROL group) participated instead in a creativity workshop. Afterwards, all the children were invited to choose, for an afternoon snack, between three familiar vs. unfamiliar foods: orange vs. apple and beetroot juice, potatoes vs. zucchini tortilla sandwich and chocolate vs. spinach cookie. The mean number of unfamiliar foods chosen per child was higher in the PURCHASE (0.70 ± 0.14) vs. CONTROL (0.19 ± 0.07) group (P = 0.003). The liking for 1 of the 3 unfamiliar foods was higher in the PURCHASE group (P < 0.05). We did not find any difference between the two groups in food intake estimation and in the levels of subjective appetite. This study demonstrates that involving children in purchasing food can help in directing their food choices towards unfamiliar foods containing vegetables. It highlights the importance of involving children in the different steps of meal preparation for decreasing food neophobia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Enabling tools for high-throughput detection of metabolites: Metabolic engineering and directed evolution applications.

    Science.gov (United States)

    Lin, Jyun-Liang; Wagner, James M; Alper, Hal S

    2017-12-01

    Within the Design-Build-Test Cycle for strain engineering, rapid product detection and selection strategies remain challenging and limit overall throughput. Here we summarize a wide variety of modalities that transduce chemical concentrations into easily measured absorbance, luminescence, and fluorescence signals. Specifically, we cover protein-based biosensors (including transcription factors), nucleic acid-based biosensors, coupled enzyme reactions, bioorthogonal chemistry, and fluorescent and chromogenic dyes and substrates as modalities for detection. We focus on the use of these methods for strain engineering and enzyme discovery and conclude with remarks on the current and future state of biosensor development for application in the metabolic engineering field. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Functional mapping of protein-protein interactions in an enzyme complex by directed evolution.

    Directory of Open Access Journals (Sweden)

    Kathrin Roderer

    Full Text Available The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS. The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84-90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84-86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes.

  2. Functional mapping of protein-protein interactions in an enzyme complex by directed evolution.

    Science.gov (United States)

    Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

    2014-01-01

    The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84-90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84-86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes.

  3. Evolution des modèles mathématiques directs appliqués aux moteurs à combustion interne Evolution of Direct Mathematical Models Applied to Internal-Combustion Engines

    Directory of Open Access Journals (Sweden)

    Rumiano N.

    2006-11-01

    Full Text Available Cet article rend compte de l'évolution présente et future des modèles mathématiques directs de simulation dans les moteurs. Ceux-ci sont basés sur la résolution des équations de Navier-Stokes, et deviennent peu à peu une nécessité surtout en ce qui concerne la combustion hétérogène. Après un aperçu sur l'état actuel des algorithmes de calcul et des sous-modèles physiques utilisés, on présente une revue des principaux codes de calcul appliqués au moteur, avec quelques-uns de leurs résultats. Après avoir évoqué les obstacles rencontrés lors de leur mise en oeuvre, on aborde l'évolution prévisible lors des prochaines années, tant pour les techniques de calcul que pour les codes eux-mêmes. This article describes the present and future evolution of direct mathematical models used for engine simulation. These models are based on the solving of Navier-Stokes equations and are gradually becoming an absolute necessity, especially with regard to heterogeneous combustion. Alter briefly describing the present state of the computing algorithms and physical submodels used, the leading computing codes applied to engines are reviewed, with some of their results. Then the stumbling blocks encountered during the implementation of these codes are described, followed by the foresable evolution in the next few years, for both computing techniques and the codes themselves.

  4. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg.

    Science.gov (United States)

    Westerbeek, R E; Van Rooden, C J; Tan, M; Van Gils, A P G; Kok, S; De Bats, M J; De Roos, A; Huisman, M V

    2008-07-01

    Accurate diagnosis of acute recurrent deep vein thrombosis (DVT) is relevant to avoid improper diagnosis and unnecessary life-long anticoagulant treatment. Compression ultrasound has high accuracy for a first episode of DVT, but is often unreliable in suspected recurrent disease. Magnetic resonance direct thrombus imaging (MR DTI) has been shown to accurately detect acute DVT. The purpose of this prospective study was to determine the MR signal change during 6 months follow-up in patients with acute DVT. This study was a prospective study of 43 consecutive patients with a first episode of acute DVT demonstrated by compression ultrasound. All patients underwent MR DTI. Follow-up was performed with MR-DTI and compression ultrasound at 3 and 6 months respectively. All data were coded, stored and assessed by two blinded observers. MR direct thrombus imaging identified acute DVT in 41 of 43 patients (sensitivity 95%). There was no abnormal MR-signal in controls, or in the contralateral extremity of patients with DVT (specificity 100%). In none of the 39 patients available at 6 months follow-up was the abnormal MR-signal at the initial acute DVT observed, whereas in 12 of these patients (30.8%) compression ultrasound was still abnormal. Magnetic resonance direct thrombus imaging normalizes over a period of 6 months in all patients with diagnosed DVT, while compression ultrasound remains abnormal in a third of these patients. MR-DTI may potentially allow for accurate detection in patients with acute suspected recurrent DVT, and this should be studied prospectively.

  5. Improved thermostability and enzyme activity of a recombinant phyA mutant phytase from Aspergillus niger N25 by directed evolution and site-directed mutagenesis.

    Science.gov (United States)

    Tang, Zizhong; Jin, Weiqiong; Sun, Rong; Liao, Yan; Zhen, Tianrun; Chen, Hui; Wu, Qi; Gou, Lin; Li, Chenlei

    2018-01-01

    We previously constructed three recombinant phyA mutant strains (PP-NP m -8, PP-NP ep -6A and I44E/T252R-PhyA), showing improved catalytic efficiency or thermostability of Aspergillus niger N25 phytase, by error-prone PCR or site-directed mutagenesis. In this study, directed evolution and site-directed mutagenesis were further applied to improve the modified phytase properties. After one-round error-prone PCR for phytase gene of PP-NP ep -6A, a single transformant, T195L/Q368E/F376Y, was obtained with the significant improvements in catalytic efficiency and thermostability. The phytase gene of T195L/Q368E/F376Y, combined with the previous mutant phytase genes of PP-NP ep -6A, PP-NP m -8 and I44E/T252R-PhyA, was then sequentially modified by DNA shuffling. Three genetically engineered strains with desirable properties were then obtained, namedQ172R, Q172R/K432R andQ368E/K432R. Among them, Q172R/K432R showed the highest thermostability with the longest half-life and the greatest remaining phytase activity after heat treatment, while Q368E/K432R showed the highest catalytic activity. Five substitutions (Q172R, T195L, Q368E, F376Y, K432R) identified from random mutagenesis were added sequentially to the phytase gene of PP-NP ep -6A to investigate how the mutant sites influence the properties of phytase. Characterization and structural analysis demonstrated that these mutations could produce cumulative or synergistic improvements in thermostability or catalytic efficiency of phytase. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Multi-omics Analysis Sheds Light on the Evolution and the Intracellular Lifestyle Strategies of Spotted Fever Group Rickettsia spp.

    Science.gov (United States)

    El Karkouri, Khalid; Kowalczewska, Malgorzata; Armstrong, Nicholas; Azza, Said; Fournier, Pierre-Edouard; Raoult, Didier

    2017-01-01

    Arthropod-borne Rickettsia species are obligate intracellular bacteria which are pathogenic for humans. Within this genus, Rickettsia slovaca and Rickettsia conorii cause frequent and potentially severe infections, whereas Rickettsia raoultii and Rickettsia massiliae cause rare and milder infections. All four species belong to spotted fever group (SFG) rickettsiae. However, R. slovaca and R. raoultii cause scalp eschar and neck lymphadenopathy (SENLAT) and are mainly associated with Dermacentor ticks, whereas the other two species cause Mediterranean spotted fever (MSF) and are mainly transmitted by Rhipicephalus ticks. To identify the potential genes and protein profiles and to understand the evolutionary processes that could, comprehensively, relate to the differences in virulence and pathogenicity observed between these four species, we compared their genomes and proteomes. The virulent and milder agents displayed divergent phylogenomic evolution in two major clades, whereas either SENLAT or MSF disease suggests a discrete convergent evolution of one virulent and one milder agent, despite their distant genetic relatedness. Moreover, the two virulent species underwent strong reductive genomic evolution and protein structural variations, as well as a probable loss of plasmid(s), compared to the two milder species. However, an abundance of mobilome genes was observed only in the less pathogenic species. After infecting Xenopus laevis cells, the virulent agents displayed less up-regulated than down-regulated proteins, as well as less number of identified core proteins. Furthermore, their similar and distinct protein profiles did not contain some genes (e.g., omp A/B and rick A) known to be related to rickettsial adhesion, motility and/or virulence, but may include other putative virulence-, antivirulence-, and/or disease-related proteins. The identified evolutionary forces herein may have a strong impact on intracellular expressions and strategies in these

  7. Environmental quality of Italian marine water by means of marine strategy framework directive (MSFD descriptor 9.

    Directory of Open Access Journals (Sweden)

    Chiara Maggi

    Full Text Available ISPRA, on behalf of the Italian Ministry of Environment, carried out the initial assessment of environmental quality status of the 3 Italian subregions (Mediterranean Sea Region on Descriptor 9. The approach adopted to define the GES started to verify that contaminants in fish and other seafood for human consumption did not exceed levels established by Community legislation (Reg. 1881/2006 and further updates. As the Marine Strategy Framework Directive (MSFD requires to use health tools to assess the environment, Italy decided to adopt a statistical range of acceptance of thresholds identified by national (D.Lgs. 152/2006 concerning water quality required for mussel farms and international legislation (Reg. 1881/2006 and further updates, which allowed to use the health results and to employ them for the assessment of environmental quality. Italy proposed that Good Environmental Status (GES is achieved when concentrations are lower than statistical range of acceptance, estimated on samples of fish and fishery products coming from only national waters. GIS-based approach a to perform different integration levels for station, cell's grid and years, was used; the elaborations allowed to judge the environmental quality good.

  8. Bilingual teaching in nursing education in China: evolution, status, and future directions.

    Science.gov (United States)

    He, Wei; Xu, Yu; Zhu, Jianhua

    2011-09-01

    Based on Chinese published literature and personal observations, this article reviews the history of bilingual teaching in nursing education in China, describes its current status and challenges, and predicts its future directions. Bilingual teaching in nursing education enjoys increasing popularity in China. The major factors that affect bilingual teaching are bilingual educators, students' English-language levels, bilingual teaching materials, and teaching models. Based on surveys of nursing schools, the English-language proficiency of the nursing educators varies greatly. The main issues with the teaching methods lie in over-translation, cramming, and limited interaction between the students and the teachers. Despite relatively inadequate English-language proficiency among Chinese nursing students, their interest can be strengthened greatly if international exchanges are available and promoted. Bilingual textbooks are more suitable in China's national context because of pricing and relevance. Although immersive bilingual teaching is the ideal, it is more feasible to begin with infiltrative bilingual teaching and move progressively towards increased English-language penetration. Future directions for improving bilingual teaching include training teaching faculty members, strengthening international exchanges, providing better bilingual study atmospheres, and gradually implementing bilingual textbooks. © 2011 Blackwell Publishing Asia Pty Ltd.

  9. Laser aided direct metal deposition of Inconel 625 superalloy: Microstructural evolution and thermal stability

    International Nuclear Information System (INIS)

    Dinda, G.P.; Dasgupta, A.K.; Mazumder, J.

    2009-01-01

    Direct metal deposition technology is an emerging laser aided manufacturing technology based on a new additive manufacturing principle, which combines laser cladding with rapid prototyping into a solid freeform fabrication process that can be used to manufacture near net shape components from their CAD files. In the present study, direct metal deposition technology was successfully used to fabricate a series of samples of the Ni-based superalloy Inconel 625. A high power CO 2 laser was used to create a molten pool on the Inconel 625 substrate into which an Inconel 625 powder stream was delivered to create a 3D object. The structure and properties of the deposits were investigated using optical and scanning electron microscopy, X-ray diffraction and microhardness test. The microstructure has been found to be columnar dendritic in nature, which grew epitaxially from the substrate. The thermal stability of the dendritic morphology was investigated in the temperature range 800-1200 deg. C. These studies demonstrate that Inconel 625 is an attractive material for laser deposition as all samples produced in this study are free from relevant defects such as cracks, bonding error and porosity.

  10. Prescription drug coupons: evolution and need for regulation in direct-to-consumer advertising.

    Science.gov (United States)

    Mackey, Tim K; Yagi, Nozomi; Liang, Bryan A

    2014-01-01

    Pharmaceutical marketing in the United States had undergone a shift from largely exclusively targeting physicians to considerable efforts in targeting patients through various forms of direct-to-consumer advertising ("DTCA"). This includes the use of DTCA in prescription drug coupons ("PDCs"), a new form of DTCA that offers discounts and rebates directly to consumers to lower costs of drug purchasing. Our examination of PDCs reveals that the use and types of PDC programs is expanding and includes promotion of the vast majority of top grossing pharmaceuticals. However, controversy regarding this emerging form of DTCA has given rise to health policy concerns about their overall impact on prescription drug expenditures for consumers, payers, and the health care system, and whether they lead to optimal long-term utilization of pharmaceuticals. In response to these concerns and the growing popularity of PDCs, what we propose here are clearer regulation and regulatory guidance for PDC DTCA use. This would include review for appropriate disclosure of marketing claims, increased transparency in PDC use for pharmaceutical pricing, and leveraging potential positive benefits of PDC use for vulnerable or underserved patient populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Laser aided direct metal deposition of Inconel 625 superalloy: Microstructural evolution and thermal stability

    Energy Technology Data Exchange (ETDEWEB)

    Dinda, G.P., E-mail: dindag@focushope.edu [Center for Advanced Technologies, Focus: HOPE, Detroit, MI 48238 (United States); Center for Laser Aided Intelligent Manufacturing, University of Michigan, Ann Arbor, MI 48109 (United States); Dasgupta, A.K. [Center for Advanced Technologies, Focus: HOPE, Detroit, MI 48238 (United States); Mazumder, J. [Center for Laser Aided Intelligent Manufacturing, University of Michigan, Ann Arbor, MI 48109 (United States)

    2009-05-25

    Direct metal deposition technology is an emerging laser aided manufacturing technology based on a new additive manufacturing principle, which combines laser cladding with rapid prototyping into a solid freeform fabrication process that can be used to manufacture near net shape components from their CAD files. In the present study, direct metal deposition technology was successfully used to fabricate a series of samples of the Ni-based superalloy Inconel 625. A high power CO{sub 2} laser was used to create a molten pool on the Inconel 625 substrate into which an Inconel 625 powder stream was delivered to create a 3D object. The structure and properties of the deposits were investigated using optical and scanning electron microscopy, X-ray diffraction and microhardness test. The microstructure has been found to be columnar dendritic in nature, which grew epitaxially from the substrate. The thermal stability of the dendritic morphology was investigated in the temperature range 800-1200 deg. C. These studies demonstrate that Inconel 625 is an attractive material for laser deposition as all samples produced in this study are free from relevant defects such as cracks, bonding error and porosity.

  12. Reverse transcriptase directs viral evolution in a deep ocean methane seep

    Science.gov (United States)

    Paul, B. G.; Bagby, S. C.

    2013-12-01

    Deep ocean methane seeps are sites of intense microbial activity, with complex communities fueled by aerobic and anaerobic methanotrophy. Methane consumption in these communities has a substantial impact on the global carbon cycle, yet little is known about their evolutionary history or their likely evolutionary trajectories in a warming ocean. As in other marine systems, viral predation and virally mediated horizontal gene transfer are expected to be major drivers of evolutionary change in these communities; however, the host cells' resistance to cultivation has impeded direct study of the viral population. We conducted a metagenomic study of viruses in the anoxic sediments of a deep methane seep in the Santa Monica Basin in the Southern California Bight. We retrieved 1660 partial viral genomes, tentatively assigning 1232 to bacterial hosts and 428 to archaea. One abundant viral genome, likely hosted by Clostridia species present in the sediment, was found to encode a diversity-generating retroelement (DGR), a module for reverse transcriptase-mediated directed mutagenesis of a distal tail fiber protein. While DGRs have previously been described in the viruses of human pathogens, where diversification of viral tail fibers permits infection of a range of host cell types, to our knowledge this is the first description of such an element in a marine virus. By providing a mechanism for massively broadening potential host range, the presence of DGRs in these systems may have a major impact on the prevalence of virally mediated horizontal gene transfer, and even on the phylogenetic distances across which genes are moved.

  13. Social evolution in micro-organisms and a Trojan horse approach to medical intervention strategies.

    Science.gov (United States)

    Brown, Sam P; West, Stuart A; Diggle, Stephen P; Griffin, Ashleigh S

    2009-11-12

    Medical science is typically pitted against the evolutionary forces acting upon infective populations of bacteria. As an alternative strategy, we could exploit our growing understanding of population dynamics of social traits in bacteria to help treat bacterial disease. In particular, population dynamics of social traits could be exploited to introduce less virulent strains of bacteria, or medically beneficial alleles into infective populations. We discuss how bacterial strains adopting different social strategies can invade a population of cooperative wild-type, considering public good cheats, cheats carrying medically beneficial alleles (Trojan horses) and cheats carrying allelopathic traits (anti-competitor chemical bacteriocins or temperate bacteriophage viruses). We suggest that exploitation of the ability of cheats to invade cooperative, wild-type populations is a potential new strategy for treating bacterial disease.

  14. Prevalence of child-directed and general audience marketing strategies on the front of beverage packaging: the case of Chile.

    Science.gov (United States)

    Mediano Stoltze, Fernanda; Barker, Joshua O; Kanter, Rebecca; Corvalán, Camila; Reyes, Marcela; Taillie, Lindsey Smith; Dillman Carpentier, Francesca R

    2018-02-01

    Front-of-package (FOP) marketing strategies of a wide variety of beverages were catalogued to examine the prevalence of each strategy prior to a sweeping Chilean restriction of child-directed marketing aimed at reducing obesity-related disease among Chile's youth. Photographs of 1005 beverage packages were quantitatively content-analysed to code whether a variety of child-directed, health-oriented and other marketing strategies (e.g. sales promotions) were present on each product's FOP. Strategies were then analysed based on beverages' product category, total sugar, energy and tax status (beverages with added sugars are taxed at different rates). Photographs were taken in six urban supermarkets in Santiago, Chile, representing five different supermarket chains. Beverages using child-directed characters or nature/fruit references were higher in total sugar and beverages with child-directed characters or childhood/family references were higher in energy than beverages without these respective strategies. Of the beverages taxed at the highest rate (greatest amount of added sugars), 49 % used nutrition and health appeals and 80 % used nature or fruit appeals. Plain waters and plain milks were less likely than other selected product categories to use health-oriented appeals or multiple FOP strategies in combination. FOP marketing on beverages varied according to the nutritional quality of the product, with heavier use of health-oriented and child-directed strategies in less healthy products. Marketing activities warrant continued observation to evaluate how industry responds to new marketing restrictions as these restrictions are evaluated in the light of existing taxes and other regulatory efforts to improve diets and reduce obesity-related disease.

  15. Reflections on the Journal of Applied Psychology for 2009 to 2014: Infrastructure, operations, innovations, impact, evolution, and desirable directions.

    Science.gov (United States)

    Kozlowski, Steve W J

    2017-03-01

    In this reflection on my experiences as editor of the Journal of Applied Psychology , I consider 6 foci including (a) information on the background, infrastructure, and mechanics of running this top-tier journal; (b) statistics on journal operations across the 7 years of editorial activity (i.e., incoming plus 6 years on the masthead); (c) innovations that my senior editorial team introduced (i.e., transparency via supplemental materials, revival of monographs, initiation of integrative conceptual reviews); (d) impact and influence with respect to articles, authors, and institutions; (e) latent sematic analysis findings to illustrate the evolution and change of journal content over a 33-year comparison period (i.e., it has evolved substantially); and desirable directions for future evolution of the journal (i.e., strengthen our scientific foundation, increase multidisciplinary linkages, focus on multilevel system dynamics as core capabilities, and improve the translation of industrial and organizational science to evidence-based practice and vice versa). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Orchestrated structure evolution: accelerating direct-write nanomanufacturing by combining top-down patterning with bottom-up growth

    Energy Technology Data Exchange (ETDEWEB)

    Kitayaporn, Sathana; Baneyx, Francois; Schwartz, Daniel T [Department of Chemical Engineering, University of Washington, Seattle, WA 98195-1750 (United States); Hoo, Ji Hao; Boehringer, Karl F, E-mail: dts@uw.edu [Department of Electrical Engineering, University of Washington, Seattle, WA 98195-1750 (United States)

    2010-05-14

    Direct-write nanomanufacturing with scanning beams and probes is flexible and can produce high quality products, but it is normally slow and expensive to raster point-by-point over a pattern. We demonstrate the use of an accelerated direct-write nanomanufacturing method called 'orchestrated structure evolution' (OSE), where a direct-write tool patterns a small number of growth 'seeds' that subsequently grow into the final thin film pattern. Through control of seed size and spacing, it is possible to vary the ratio of 'top-down' to 'bottom-up' character of the patterning processes, ranging from conventional top-down raster patterning to nearly pure bottom-up space-filling via seed growth. Electron beam lithography (EBL) and copper electrodeposition were used to demonstrate trade-offs between process time and product quality over nano- to microlength scales. OSE can reduce process times for high-cost EBL patterning by orders of magnitude, at the expense of longer (but inexpensive) copper electrodeposition processing times. We quantify the degradation of pattern quality that accompanies fast OSE patterning by measuring deviations from the desired patterned area and perimeter. We also show that the density of OSE-induced grain boundaries depends upon the seed separation and size. As the seed size is reduced, the uniformity of an OSE film becomes more dependent on details of seed nucleation processes than normally seen for conventionally patterned films.

  17. Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

    Science.gov (United States)

    Pandey, Ramesh Prasad; Parajuli, Prakash; Koffas, Mattheos A G; Sohng, Jae Kyung

    2016-01-01

    In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Simulation of microstructural evolution in directional solidification of Ti-45at.%Al alloy using cellular automaton method

    Directory of Open Access Journals (Sweden)

    Wang Kuangfei

    2010-02-01

    Full Text Available The microstructural evolution of Ti-45 at.%Al alloy during directional solidification was simulated by applying a solute diffusion controlled solidification model. The obtained results have shown that under high thermal gradients the stable primary spacing can be adjusted via branching or competitive growth. For dendritic structures formed under a high thermal gradient, the secondary dendrite arms are developed not very well in many cases due to the branching mechanism under a constrained dendritic growth condition. Furthermore, it has been observed that, with increasing pulling velocity, there exists a cell/dendrite transition region consisting of cells and dendrites, which varies with the thermal gradient in a contradicting way, i.e. increase of the thermal gradient leading to the decrease of the range of the transition region. The simulations agree reasonably well with experiment results.

  19. A New Design Strategy for Observing Lithium Oxide Growth-Evolution Interactions Using Geometric Catalyst Positioning.

    Science.gov (United States)

    Ryu, Won-Hee; Gittleson, Forrest S; Li, Jinyang; Tong, Xiao; Taylor, André D

    2016-08-10

    Understanding the catalyzed formation and evolution of lithium-oxide products in Li-O2 batteries is central to the development of next-generation energy storage technology. Catalytic sites, while effective in lowering reaction barriers, often become deactivated when placed on the surface of an oxygen electrode due to passivation by solid products. Here we investigate a mechanism for alleviating catalyst deactivation by dispersing Pd catalytic sites away from the oxygen electrode surface in a well-structured anodic aluminum oxide (AAO) porous membrane interlayer. We observe the cross-sectional product growth and evolution in Li-O2 cells by characterizing products that grow from the electrode surface. Morphological and structural details of the products in both catalyzed and uncatalyzed cells are investigated independently from the influence of the oxygen electrode. We find that the geometric decoration of catalysts far from the conductive electrode surface significantly improves the reaction reversibility by chemically facilitating the oxidation reaction through local coordination with PdO surfaces. The influence of the catalyst position on product composition is further verified by ex situ X-ray photoelectron spectroscopy and Raman spectroscopy in addition to morphological studies.

  20. CONSIDERATIONS CONCERNING THE EVOLUTION OF THE LOCAL DEVELOPMENT STRATEGY OF SOME LEADER TERRITORIES IN ARAD COUNTY

    Directory of Open Access Journals (Sweden)

    Radu Lucian Blaga

    2014-12-01

    Full Text Available Romanian National Rural Development Programme (NRDP 2007-2013 is the document, which applies EU Common Agricultural Policy in Romania as EU member state. LEADER, as part of EU Common Agricultural Policy was developed like territory planning policies focused on the rural area of intervention. It proved more effective and productive, being decided and implemented at local level by the local actors, using clear and transparent procedures for the evaluation of strategic objectives and plans, having the support of local governments and technical assistance necessary to transmit best practices. The European Agricultural Fund for Rural Development (EAFRD finances investments in LEADER axis, using intervention areas (priority 1, priority 2 and priority 3 and related measures to NRDP. These measures can be found in a variable degree at the level of the Local Development Strategy (LDS elaborated by The Local Action Groups (LAGs, LEADER territory concerned. Based on these issues, the paper seeks to present some practical considerations of the assessment of the LAG‟s activities in the implementation of strategy, scientifically linked to the portfolio analysis activities (intervention areas and measures that compound the Local Development Strategy of some LEADER entities of the Arad County. The evaluation used outcome indicators for implementation of the Strategy.

  1. the evolution of strategy: thinking war from antiquity to the present

    African Journals Online (AJOL)

    ismith

    historical sources to anchor the theoretical departure of the work further, and ... critical stances about the utility of armed forces seem to have entered a growth ... of strategy within the politico-military environment, although Heuser argues that it ... discussions influence decision-making that ultimately affects and in fact tailors.

  2. Protein consensus-based surface engineering (ProCoS): a computer-assisted method for directed protein evolution.

    Science.gov (United States)

    Shivange, Amol V; Hoeffken, Hans Wolfgang; Haefner, Stefan; Schwaneberg, Ulrich

    2016-12-01

    Protein consensus-based surface engineering (ProCoS) is a simple and efficient method for directed protein evolution combining computational analysis and molecular biology tools to engineer protein surfaces. ProCoS is based on the hypothesis that conserved residues originated from a common ancestor and that these residues are crucial for the function of a protein, whereas highly variable regions (situated on the surface of a protein) can be targeted for surface engineering to maximize performance. ProCoS comprises four main steps: ( i ) identification of conserved and highly variable regions; ( ii ) protein sequence design by substituting residues in the highly variable regions, and gene synthesis; ( iii ) in vitro DNA recombination of synthetic genes; and ( iv ) screening for active variants. ProCoS is a simple method for surface mutagenesis in which multiple sequence alignment is used for selection of surface residues based on a structural model. To demonstrate the technique's utility for directed evolution, the surface of a phytase enzyme from Yersinia mollaretii (Ymphytase) was subjected to ProCoS. Screening just 1050 clones from ProCoS engineering-guided mutant libraries yielded an enzyme with 34 amino acid substitutions. The surface-engineered Ymphytase exhibited 3.8-fold higher pH stability (at pH 2.8 for 3 h) and retained 40% of the enzyme's specific activity (400 U/mg) compared with the wild-type Ymphytase. The pH stability might be attributed to a significantly increased (20 percentage points; from 9% to 29%) number of negatively charged amino acids on the surface of the engineered phytase.

  3. Direct traumatic carotid cavernous fistula: angiographic classification and treatment strategies. Study of 172 cases.

    Science.gov (United States)

    Chi, Cuong Tran; Nguyen, Dang; Duc, Vo Tan; Chau, Huynh Hong; Son, Vo Tan

    2014-01-01

    We report our experience in treatment of traumatic direct carotid cavernous fistula (CCF) via endovascular intervention. We hereof recommend an additional classification system for type A CCF and suggest respective treatment strategies. Only type A CCF patients (Barrow's classification) would be recruited for the study. Based on the angiographic characteristics of the CCF, we classified type A CCF into three subtypes including small size, medium size and large size fistula depending on whether there was presence of the anterior carotid artery (ACA) and/or middle carotid artery (MCA). Angiograms with opacification of both ACA and MCA were categorized as small size fistula. Angiograms with opacification of either ACA or MCA were categorized as medium size fistula and those without opacification of neither ACA nor MCA were classified as large size fiatula. After the confirm angiogram, endovascular embolization would be performed impromptu using detachable balloon, coils or both. All cases were followed up for complication and effect after the embolization. A total of 172 direct traumatic CCF patients were enrolled. The small size fistula was accountant for 12.8% (22 cases), medium size 35.5% (61 cases) and large size fistula accountant for 51.7% (89 cases). The successful rate of fistula occlusion under endovascular embolization was 94% with preservation of the carotid artery in 70%. For the treatment of each subtype, a total of 21/22 cases of the small size fistulas were successfully treated using coils alone. The other single case of small fistula was defaulted. Most of the medium and large size fistulas were cured using detachable balloons. When the fistula sealing could not be obtained using detachable balloon, coils were added to affirm the embolization of the cavernous sinus via venous access. There were about 2.9% of patient experienced direct carotid artery puncture and 0.6% puncture after carotid artery cut-down exposure. About 30% of cases experienced

  4. Branching-induced grain boundary evolution during directional solidification of columnar dendritic grains

    International Nuclear Information System (INIS)

    Guo, Chunwen; Li, Junjie; Yu, Honglei; Wang, Zhijun; Lin, Xin; Wang, Jincheng

    2017-01-01

    We present an investigation of secondary and tertiary branching behavior in diverging grain boundaries (GBs) between two columnar dendritic grains with different crystallographic orientations, both by two-dimensional phase-field simulations and thin-sample experiments. The stochasticity of the GB trajectories and the statistically averaged GB orientations were analyzed in detail. The side-branching dynamics and subsequent branch competition behaviors found in the simulations agreed well with the experimental results. When the orientations of two grains are given, the experimental results indicated that the average GB orientation was independent of the pulling velocity in the dendritic growth regime. The simulation and experimental results, as well as the results reported in the literature exhibit a uniform relation between the percentage of the whole gap region occupied by the favorably oriented grain and the difference in the absolute values of the secondary arm growth directions of the two competitive grains. By describing such a uniform relation with a simple fitting equation, we proposed a simple analytical model for the GB orientation at diverging GBs, which gives a more accurate description of GB orientation selection than the existing models.

  5. Learning strategies in excellent and average university students. Their evolution over the first year of the career

    Directory of Open Access Journals (Sweden)

    Gargallo, Bernardo

    2012-12-01

    Full Text Available The aim of this paper was to analyze the evolution of learning strategies of two groups of students, excellent and average, from 11 degrees of the UPV (Valencia/Spain in their freshman year. We used the CEVEAPEU questionnaire. The results confirmed the availability of better strategies of excellent students and also the existence of evolutionary patterns in which affective-emotional strategies decrease, such as value of the task or internal attributions, and that others increase, such as extrinsic motivation and external attributions. It seems that the student does not meet your expectations in the new context and professors have important responsibilities. El objetivo de este trabajo era analizar la evolución de las estrategias de aprendizaje de estudiantes excelentes y medios de 11 titulaciones de la V (Valencia, en su primer año. Los alumnos contestaron el cuestionario CEVEAPEU en tres momentos. Los resultados constataron mejores estrategias en los estudiantes excelentes. También confirmaron patrones evolutivos en que estrategias afectivo-emotivas relevantes disminuyen, como valor de la tarea o atribuciones internas, y se incrementan otras, como motivación extrínseca y atribuciones externas. Parece que el estudiante no satisface sus expectativas en el proceso de adaptación al nuevo contexto y ahí los profesores tienen responsabilidades ineludibles.

  6. Overview of eutrophication indicators to assess environmental status within the European Marine Strategy Framework Directive

    Science.gov (United States)

    Ferreira, João G.; Andersen, Jesper H.; Borja, Angel; Bricker, Suzanne B.; Camp, Jordi; Cardoso da Silva, Margarida; Garcés, Esther; Heiskanen, Anna-Stiina; Humborg, Christoph; Ignatiades, Lydia; Lancelot, Christiane; Menesguen, Alain; Tett, Paul; Hoepffner, Nicolas; Claussen, Ulrich

    2011-06-01

    In 2009, following approval of the European Marine Strategy Framework Directive (MSFD, 2008/56/EC), the European Commission (EC) created task groups to develop guidance for eleven quality descriptors that form the basis for evaluating ecosystem function. The objective was to provide European countries with practical guidelines for implementing the MSFD, and to produce a Commission Decision that encapsulated key points of the work in a legal framework. This paper presents a review of work carried out by the eutrophication task group, and reports our main findings to the scientific community. On the basis of an operational, management-oriented definition, we discuss the main methodologies that could be used for coastal and marine eutrophication assessment. Emphasis is placed on integrated approaches that account for physico-chemical and biological components, and combine both pelagic and benthic symptoms of eutrophication, in keeping with the holistic nature of the MSFD. We highlight general features that any marine eutrophication model should possess, rather than making specific recommendations. European seas range from highly eutrophic systems such as the Baltic to nutrient-poor environments such as the Aegean Sea. From a physical perspective, marine waters range from high energy environments of the north east Atlantic to the permanent vertical stratification of the Black Sea. This review aimed to encapsulate that variability, recognizing that meaningful guidance should be flexible enough to accommodate the widely differing characteristics of European seas, and that this information is potentially relevant in marine ecosystems worldwide. Given the spatial extent of the MSFD, innovative approaches are required to allow meaningful monitoring and assessment. Consequently, substantial logistic and financial challenges will drive research in areas such as remote sensing of harmful algal blooms, in situ sensor development, and mathematical models. Our review takes into

  7. Indicator Properties of Baltic Zooplankton for Classification of Environmental Status within Marine Strategy Framework Directive.

    Science.gov (United States)

    Gorokhova, Elena; Lehtiniemi, Maiju; Postel, Lutz; Rubene, Gunta; Amid, Callis; Lesutiene, Jurate; Uusitalo, Laura; Strake, Solvita; Demereckiene, Natalja

    2016-01-01

    The European Marine Strategy Framework Directive requires the EU Member States to estimate the level of anthropogenic impacts on their marine systems using 11 Descriptors. Assessing food web response to altered habitats is addressed by Descriptor 4 and its indicators, which are being developed for regional seas. However, the development of simple foodweb indicators able to assess the health of ecologically diverse, spatially variable and complex interactions is challenging. Zooplankton is a key element in marine foodwebs and thus comprise an important part of overall ecosystem health. Here, we review work on zooplankton indicator development using long-term data sets across the Baltic Sea and report the main findings. A suite of zooplankton community metrics were evaluated as putative ecological indicators that track community state in relation to Good Environmental Status (GES) criteria with regard to eutrophication and fish feeding conditions in the Baltic Sea. On the basis of an operational definition of GES, we propose mean body mass of zooplankton in the community in combination with zooplankton stock measured as either abundance or biomass to be applicable as an integrated indicator that could be used within the Descriptor 4 in the Baltic Sea. These metrics performed best in predicting zooplankton being in-GES when considering all datasets evaluated. However, some other metrics, such as copepod biomass, the contribution of copepods to the total zooplankton biomass or biomass-based Cladocera: Copepoda ratio, were equally reliable or even superior in certain basin-specific assessments. Our evaluation suggests that in several basins of the Baltic Sea, zooplankton communities currently appear to be out-of-GES, being comprised by smaller zooplankters and having lower total abundance or biomass compared to the communities during the reference conditions; however, the changes in the taxonomic structure underlying these trends vary widely across the sea basins due to

  8. Morphology evolution of PS-b-PDMS block copolymer and its hierarchical directed self-assembly on block copolymer templates

    DEFF Research Database (Denmark)

    Rasappa, Sozaraj; Schulte, Lars; Borah, Dipu

    2018-01-01

    Cylinder-forming polystyrene-block-polydimethylsiloxane (PS-b-PDMS, 27.2k-b-11.7k, SD39) block copolymer having a total molecular weight of 39 kg mol−1 was exploited to achieve in-plane morphologies of lines, dots and antidots. Brush-free self-assembly of the SD39 on silicon substrates was invest...... substrates provides a simplified method for surface nanopatterning, templated growth of nanomaterials and nanofabrication....... the pattern into the underlying substrate. Directed self-assembly and hierarchical directed self-assembly on block copolymer templates for confinement of dots was successfully demonstrated. The strategy for achieving multiple morphologies using one BCP by mere choice of the annealing solvents on unmodified...

  9. Evolution of optimal Lévy-flight strategies in human mental searches

    Science.gov (United States)

    Radicchi, Filippo; Baronchelli, Andrea

    2012-06-01

    Recent analysis of empirical data [Radicchi, Baronchelli, and Amaral, PloS ONE1932-620310.1371/journal.pone.0029910 7, e029910 (2012)] showed that humans adopt Lévy-flight strategies when exploring the bid space in online auctions. A game theoretical model proved that the observed Lévy exponents are nearly optimal, being close to the exponent value that guarantees the maximal economical return to players. Here, we rationalize these findings by adopting an evolutionary perspective. We show that a simple evolutionary process is able to account for the empirical measurements with the only assumption that the reproductive fitness of the players is proportional to their search ability. Contrary to previous modeling, our approach describes the emergence of the observed exponent without resorting to any strong assumptions on the initial searching strategies. Our results generalize earlier research, and open novel questions in cognitive, behavioral, and evolutionary sciences.

  10. Why Keep Changing Explaining the Evolution of Singapore’s Military Strategy Since Independence

    Science.gov (United States)

    2017-03-01

    have agreed that the Dolphin strategy, with the 3G SAF as its core, is characterized by the use of “ intelligence , speed, and maneuverability in a...secure investor confidence. Any “loss of confidence in the republic’s stability or security would seriously damage its economic health.”55 The...the Singaporean leadership’s acknowledgement of the need to secure investor confidence and also of the increasing importance of the maritime domain

  11. The Evolution of the U.S. Navy’s Maritime Strategy, 1977-1986

    Science.gov (United States)

    2003-01-01

    Studies Group was designed to try to surmount the natural and artificial barriers to a free exchange of thinking that had developed over the years. In many...to The Maritime Strategy are listed separately, to aid the reader/researcher. (Admittedly, this and other artificial ty- pological devices run against... Intellignece Vessel) 124, 145, 290, 303 airborne early warning (AEW) 163, 173 airborne warning and control system (AWACS) 19, 163 aircraft 10, 17–19, 27

  12. Understanding International Product Strategy in Multinational Corporations through New Product Development Approaches and Evolution

    OpenAIRE

    Liu, Yang; Shi, Yongjiang

    2017-01-01

    International product strategy regarding global standardisation and local adaptation is one of the challenges faced by multinational corporations (MNCs). Studies in this area have tested the antecedents and consequences of standardisation/adaptation, but lack a new product development (NPD) perspective. In this study, we explore how product standardisation/adaptation is determined in the NPD context. Through a qualitative case study of four MNCs, we found three NPD approaches: multi-local, ad...

  13. The rock-paper-scissors game and the evolution of alternative male strategies

    Science.gov (United States)

    Sinervo, B.; Lively, C. M.

    1996-03-01

    MANY species exhibit colour polymorphisms associated with alternative male reproductive strategies, including territorial males and 'sneaker males' that behave and look like females1-3. The prevalence of multiple morphs is a challenge to evolutionary theory because a single strategy should prevail unless morphs have exactly equal fitness4,5 or a fitness advantage when rare6,7. We report here the application of an evolutionary stable strategy model to a three-morph mating system in the side-blotched lizard. Using parameter estimates from field data, the model predicted oscillations in morph frequency, and the frequencies of the three male morphs were found to oscillate over a six-year period in the field. The fitnesses of each morph relative to other morphs were non-transitive in that each morph could invade another morph when rare, but was itself invadable by another morph when common. Concordance between frequency-dependent selection and the among-year changes in morph fitnesses suggest that male interactions drive a dynamic 'rock-paper-scissors' game7.

  14. Cathodic electrochemical activation of Co3O4 nanoarrays: a smart strategy to significantly boost the hydrogen evolution activity.

    Science.gov (United States)

    Yang, Li; Zhou, Huang; Qin, Xin; Guo, Xiaodong; Cui, Guanwei; Asiri, Abdullah M; Sun, Xuping

    2018-02-22

    Co(hydro)oxides show unsatisfactory catalytic activity for the hydrogen evolution reaction (HER) in alkaline media, and it is thus highly desirable but still remains a challenge to design and develop Co(hydro)oxide derived materials as superb hydrogen-evolving catalysts using a facile, rapid and less energy-intensive method. Here, we propose a cathodic electrochemical activation strategy toward greatly boosted HER activity of a Co 3 O 4 nanoarray via room-temperature cathodic polarization in sodium hypophosphite solution. After activation, the overpotential significantly decreases from 260 to 73 mV to drive a geometrical catalytic current density of 10 mA cm -2 in 1.0 M KOH. Notably, this activated electrode also shows strong long-term electrochemical durability with the retention of its catalytic activity at 100 mA cm -2 for at least 40 h.

  15. An improved artificial bee colony algorithm based on balance-evolution strategy for unmanned combat aerial vehicle path planning.

    Science.gov (United States)

    Li, Bai; Gong, Li-gang; Yang, Wen-lun

    2014-01-01

    Unmanned combat aerial vehicles (UCAVs) have been of great interest to military organizations throughout the world due to their outstanding capabilities to operate in dangerous or hazardous environments. UCAV path planning aims to obtain an optimal flight route with the threats and constraints in the combat field well considered. In this work, a novel artificial bee colony (ABC) algorithm improved by a balance-evolution strategy (BES) is applied in this optimization scheme. In this new algorithm, convergence information during the iteration is fully utilized to manipulate the exploration/exploitation accuracy and to pursue a balance between local exploitation and global exploration capabilities. Simulation results confirm that BE-ABC algorithm is more competent for the UCAV path planning scheme than the conventional ABC algorithm and two other state-of-the-art modified ABC algorithms.

  16. An Improved Artificial Bee Colony Algorithm Based on Balance-Evolution Strategy for Unmanned Combat Aerial Vehicle Path Planning

    Directory of Open Access Journals (Sweden)

    Bai Li

    2014-01-01

    Full Text Available Unmanned combat aerial vehicles (UCAVs have been of great interest to military organizations throughout the world due to their outstanding capabilities to operate in dangerous or hazardous environments. UCAV path planning aims to obtain an optimal flight route with the threats and constraints in the combat field well considered. In this work, a novel artificial bee colony (ABC algorithm improved by a balance-evolution strategy (BES is applied in this optimization scheme. In this new algorithm, convergence information during the iteration is fully utilized to manipulate the exploration/exploitation accuracy and to pursue a balance between local exploitation and global exploration capabilities. Simulation results confirm that BE-ABC algorithm is more competent for the UCAV path planning scheme than the conventional ABC algorithm and two other state-of-the-art modified ABC algorithms.

  17. Strategies for Selecting Routes through Real-World Environments: Relative Topography, Initial Route Straightness, and Cardinal Direction.

    Directory of Open Access Journals (Sweden)

    Tad T Brunyé

    Full Text Available Previous research has demonstrated that route planners use several reliable strategies for selecting between alternate routes. Strategies include selecting straight rather than winding routes leaving an origin, selecting generally south- rather than north-going routes, and selecting routes that avoid traversal of complex topography. The contribution of this paper is characterizing the relative influence and potential interactions of these strategies. We also examine whether individual differences would predict any strategy reliance. Results showed evidence for independent and additive influences of all three strategies, with a strong influence of topography and initial segment straightness, and relatively weak influence of cardinal direction. Additively, routes were also disproportionately selected when they traversed relatively flat regions, had relatively straight initial segments, and went generally south rather than north. Two individual differences, extraversion and sense of direction, predicted the extent of some effects. Under real-world conditions navigators indeed consider a route's initial straightness, cardinal direction, and topography, but these cues differ in relative influence and vary in their application across individuals.

  18. The Main Directions of the Structural Defragmentation of the State Development Strategy of the NIS of Ukraine

    Directory of Open Access Journals (Sweden)

    Melnyk Alexander G.

    2018-03-01

    Full Text Available The article considers the scientific-methodical approach to bridging of gaps on the main directions, in systems of mechanisms and instruments of the State strategy for development of the National Innovation Strategy (NIS, caused by breaks in the system of interactions by elements of its organizational, technological, and institutional structure. This situation in the innovation system is defined as fragmentation of the basic structures of the NIS, which is interrelated by fragmentation of multi-level development strategies for development of the NIS. The most fragmented directions of the State strategy for development of the NIS of Ukraine are defined, among which the system of transfer of technologies and absence of corresponding strategic priorities, technological modernization of industry, integration of the research sphere into the world innovation space, creation of the high-tech sector of NIS. The main directions of structural defragmentation of the State Strategy for Development of the NIS are proposed: organization of innovation process, formation of development institutions, clustering of scientific and production sectors of the NIS, formation of environment to achieve technological leadership.

  19. The evolution of health warning labels on cigarette packs: the role of precedents, and tobacco industry strategies to block diffusion

    Science.gov (United States)

    Hiilamo, Heikki; Crosbie, Eric; Glantz, Stanton A

    2013-01-01

    Objective To analyse the evolution and diffusion of health warnings on cigarette packs around the world, including tobacco industry attempts to block this diffusion. Methods We analysed tobacco industry documents and public sources to construct a database on the global evolution and diffusion of health warning labels from 1966 to 2012, and also analysed industry strategies. Results Health warning labels, especially labels with graphic elements, threaten the tobacco industry because they are a low-cost, effective measure to reduce smoking. Multinational tobacco companies did not object to voluntary innocuous warnings with ambiguous health messages, in part because they saw them as offering protection from lawsuits and local packaging regulations. The companies worked systematically at the international level to block or weaken warnings once stronger more specific warnings began to appear in the 1970s. Since 1985 in Iceland, the tobacco industry has been aware of the effectiveness of graphic health warning labels (GWHL). The industry launched an all-out attack in the early 1990s to prevent GHWLs, and was successful in delaying GHWLs internationally for nearly 10 years. Conclusions Beginning in 2005, as a result of the World Health Organisation Framework Convention on Tobacco Control (FCTC), GHWLs began to spread. Effective implementation of FCTC labelling provisions has stimulated diffusion of strong health warning labels despite industry opposition. PMID:23092884

  20. The evolution of emissions trading in the EU. Tensions between national trading schemes and the proposed EU directive

    International Nuclear Information System (INIS)

    Boemare, Catherine; Quirion, Philippe; Sorrell, Steve

    2003-12-01

    The EU is pioneering the development of greenhouse gas emissions trading, but there is a tension between the 'top-down' and 'bottom-up' evolution of trading schemes. While the Commission is introducing a European emissions trading scheme (EU ETS) in 2005, several member states have already introduced negotiated agreements that include trading arrangements. Typically, these national schemes have a wider scope than the proposed EU directive and allow firms to use relative rather than absolute targets. The coexistence of 'top-down' and 'bottom-up' trading schemes may create some complex problems of policy interaction. This paper explores the potential interactions between the EU ETS and the negotiated agreements in France and UK and uses these to illustrate some important generic issues. The paper first describes the proposed EU directive, outlines the UK and French policies and compares their main features to the EU ETS. It then discusses how the national and European policies may interact in practice. Four issues are highlighted, namely, double regulation, double counting of emission reductions, equivalence of effort and linking trading schemes. The paper concludes with some recommendations for the future development of UK and French climate policy

  1. Directed evolution of Oenococcus oeni strains for more efficient malolactic fermentation in a multi-stressor wine environment.

    Science.gov (United States)

    Jiang, Jiao; Sumby, Krista M; Sundstrom, Joanna F; Grbin, Paul R; Jiranek, Vladimir

    2018-08-01

    High concentrations of ethanol, low pH, the presence of sulfur dioxide and some polyphenols have been reported to inhibit Oenococcus oeni growth, thereby negatively affecting malolactic fermentation (MLF) of wine. In order to generate superior O. oeni strains that can conduct more efficient MLF, despite these multiple stressors, a continuous culture approach was designed to directly evolve an existing ethanol tolerant O. oeni strain, A90. The strain was grown for ∼350 generations in a red wine-like environment with increasing levels of stressors. Three strains were selected from screening experiments based on their completion of fermentation in a synthetic wine/wine blend with 15.1% (v/v) ethanol, 26 mg/L SO 2 at pH 3.35 within 160 h, while the parent strain fermented no more than two thirds of l-malic acid in this medium. These superior strains also fermented faster and/or had a larger population in four different wines. A reduced or equivalent amount of the undesirable volatile, acetic acid, was produced by the optimised strains compared to a commercial strain in Mouvedre and Merlot wines. These findings demonstrate the feasibility of using directed evolution as a tool to generate more efficient MLF starters tailored for wines with multiple stressors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Implementing the Marine Strategy Framework Directive: A policy perspective on regulatory, institutional and stakeholder impediments to effective implementation

    NARCIS (Netherlands)

    Leeuwen, van J.; Raakjaer, J.; Hoof, van L.J.W.; Tatenhove, van J.P.M.; Long, R.; Ounanian, K.

    2014-01-01

    The implementation of the European Union (EU) Marine Strategy Framework Directive (MSFD) requires EU Member States to draft a program of measures to achieve Good Environmental Status (GES). Central argument of this paper, based on an analysis of the unique, holistic character of the MSFD, is that

  3. Key challenges in the combat of human trafficking : Evaluating the EU trafficking strategy and EU trafficking directive

    NARCIS (Netherlands)

    Bosma, Alice; Rijken, Conny

    2016-01-01

    The problem of trafficking in human beings (THB) is still omnipresent in Europe, despite the numerous preventive and retributive actions taken. This article evaluates the two most important EU-instruments to combat trafficking: the EU Directive and the EU Strategy. Based on secondary analysis of

  4. Use of time and materials and cost reimbursement subcontracts for remedial actions under the alternative remedial contracting strategy contracts. Directive

    International Nuclear Information System (INIS)

    1992-01-01

    The directive is intended to establish agency guidance on the use of time and materials and cost reimbursement contracts for remedial actions in general and to provide specific instruction regarding the use of these approaches in subcontracting under the Alternative Remedial Contracting Strategy (ARCS) contracts

  5. The evolution of different maternal investment strategies in two closely related desert vertebrates

    Science.gov (United States)

    Ennen, Joshua R.; Lovich, Jeffrey E.; Averill-Murray, Roy C.; Yackulic, Charles B.; Agha, Mickey; Loughran, Caleb; Tennant, Laura A.; Sinervo, Barry

    2017-01-01

    We compared egg size phenotypes and tested several predictions from the optimal egg size (OES) and bet-hedging theories in two North American desert-dwelling sister tortoise taxa, Gopherus agassizii and G. morafkai, that inhabit different climate spaces: relatively unpredictable and more predictable climate spaces, respectively. Observed patterns in both species differed from the predictions of OES in several ways. Mean egg size increased with maternal body size in both species. Mean egg size was inversely related to clutch order in G. agassizii, a strategy more consistent with the within-generation hypothesis arising out of bet-hedging theory or a constraint in egg investment due to resource availability, and contrary to theories of density dependence, which posit that increasing hatchling competition from later season clutches should drive selection for larger eggs. We provide empirical evidence that one species, G. agassizii, employs a bet-hedging strategy that is a combination of two different bet-hedging hypotheses. Additionally, we found some evidence for G. morafkai employing a conservative bet-hedging strategy. (e.g., lack of intra- and interclutch variation in egg size relative to body size). Our novel adaptive hypothesis suggests the possibility that natural selection favors smaller offspring in late-season clutches because they experience a more benign environment or less energetically challenging environmental conditions (i.e., winter) than early clutch progeny, that emerge under harsher and more energetically challenging environmental conditions (i.e., summer). We also discuss alternative hypotheses of sexually antagonistic selection, which arise from the trade-offs of son versus daughter production that might have different optima depending on clutch order and variation in temperature-dependent sex determination (TSD) among clutches. Resolution of these hypotheses will require long-term data on fitness of sons versus daughters as a function of

  6. Sources Of Evolution Of The Japan Air Self Defense Force’s Strategy

    Science.gov (United States)

    2016-12-01

    national security. • Second is the battle space of war. “Defensive defense” strategy conducts war definitely in its territory and bears that most of its...russia-in- 2016/. 271Ankit Panda , “East China Sea: Japan Reacts as Chinese Air Force Conducts Miyako Strait Drill,” Diplomat, September 26, 2016...June 22, 2016. http://www.voanews.com/a/north-korea- failed-missile-tests-show-real-progress/3386692.html. Panda , Ankit. “East China Sea: Japan Reacts

  7. Investing in the Future World Order: Geoeconomic Strategy and Foreign Direct Investment

    Science.gov (United States)

    2017-06-01

    Geoeconomic Strategies and FDI Regulation Thus, what is of supreme importance in war is to attack the enemy’s strategy. Sun Tzu Sun Tzu’s infamous...106 BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112...Investment, 262. 111 Bibliography “About Us | International Forum of Sovereign Wealth Funds.” Accessed May 21, 2017. http://www.ifswf.org

  8. Building Bridges: Seeking Structure and Direction for Higher Education Motivated Learning Strategy Models

    Science.gov (United States)

    Fryer, Luke K.

    2017-01-01

    Many of our current higher education (HE) learning strategy models intersect at important points. At the same time, these theories also often demonstrate important unique perspectives on student learning within HE. Currently, research with one learning strategy model rarely leads to developments in others, as each group of researchers works in…

  9. Social Mobile Marketing: Evolution of Communication Strategies in the Web 2.0 Era

    Directory of Open Access Journals (Sweden)

    Stefano Franco

    2014-07-01

    Full Text Available Increasingly faster communicational streams - that ease interactions and allow agents to considerably enhance their own informational assets - characterize the era in which we live. The research about new media, mobile and social technologies is the driver of this changes that implements a revolution of the content management, of the information accessibility and of the relationships interactivity. These characteristics don’t leave the agents unresponsive and it is interesting and fitting to understand the tools available to firms and institutions and the communicational and marketing policies that organizations put to use to achieve their goals. In this context we want to find strategic and operational models to support organizations decisions about markets and territories. The purpose of this article is to understand how small organizations can utilize networks that characterize new trends in marketing. We conclude by providing some thoughts on the future evolution of the research in this field also with reference to the smart city that can exploit social mobile marketing for promotion of the territory and social participation.I

  10. Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity.

    Science.gov (United States)

    Brüssow, Harald

    2007-08-01

    Bacteriophages and protists are major causes of bacterial mortality. Genomics suggests that phages evolved well before eukaryotic protists. Bacteria were thus initially only confronted with phage predators. When protists evolved, bacteria were caught between two types of predators. One successful antigrazing strategy of bacteria was the elaboration of toxins that would kill the grazer. The released cell content would feed bystander bacteria. I suggest here that, to fight grazing protists, bacteria teamed up with those phage predators that concluded at least a temporary truce with them in the form of lysogeny. Lysogeny was perhaps initially a resource management strategy of phages that could not maintain infection chains. Subsequently, lysogeny might have evolved into a bacterium-prophage coalition attacking protists, which became a food source for them. When protists evolved into multicellular animals, the lysogenic bacteria tracked their evolving food source. This hypothesis could explain why a frequent scheme of bacterial pathogenicity is the survival in phagocytes, why a significant fraction of bacterial pathogens have prophage-encoded virulence genes, and why some virulence factors of animal pathogens are active against unicellular eukaryotes. Bacterial pathogenicity might thus be one playing option of the stone-scissor-paper game played between phages-bacteria-protists, with humans getting into the crossfire.

  11. Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template.

    Science.gov (United States)

    Gouran, Hossein; Chakraborty, Sandeep; Rao, Basuthkar J; Asgeirsson, Bjarni; Dandekar, Abhaya

    2014-01-01

    Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC), implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF). In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

  12. Experimental evolution of recombination and crossover interference in Drosophila caused by directional selection for stress-related traits.

    Science.gov (United States)

    Aggarwal, Dau Dayal; Rashkovetsky, Eugenia; Michalak, Pawel; Cohen, Irit; Ronin, Yefim; Zhou, Dan; Haddad, Gabriel G; Korol, Abraham B

    2015-11-27

    Population genetics predicts that tight linkage between new and/or pre-existing beneficial and deleterious alleles should decrease the efficiency of natural selection in finite populations. By decoupling beneficial and deleterious alleles and facilitating the combination of beneficial alleles, recombination accelerates the formation of high-fitness genotypes. This may impose indirect selection for increased recombination. Despite the progress in theoretical understanding, interplay between recombination and selection remains a controversial issue in evolutionary biology. Even less satisfactory is the situation with crossover interference, which is a deviation of double-crossover frequency in a pair of adjacent intervals from the product of recombination rates in the two intervals expected on the assumption of crossover independence. Here, we report substantial changes in recombination and interference in three long-term directional selection experiments with Drosophila melanogaster: for desiccation (~50 generations), hypoxia, and hyperoxia tolerance (>200 generations each). For all three experiments, we found a high interval-specific increase of recombination frequencies in selection lines (up to 40-50% per interval) compared to the control lines. We also discovered a profound effect of selection on interference as expressed by an increased frequency of double crossovers in selection lines. Our results show that changes in interference are not necessarily coupled with increased recombination. Our results support the theoretical predictions that adaptation to a new environment can promote evolution toward higher recombination. Moreover, this is the first evidence of selection for different recombination-unrelated traits potentially leading, not only to evolution toward increased crossover rates, but also to changes in crossover interference, one of the fundamental features of recombination.

  13. The Stressors and Coping Strategies of Older Adults With Persistent Atrial Fibrillation Prior to and Following Direct Current Cardioversion.

    Science.gov (United States)

    Rush, Kathy L; Hatt, Linda; Shay, Matt; Gorman, Nicole; Laberge, Carol G; Reid, R Colin; Wilson, Ryan

    2017-09-01

    The purpose of this study was to explore the stressors and coping strategies of older adults with persistent atrial fibrillation (AF) before and after direct current cardioversion. The study used a qualitative descriptive design. Sixteen patients were recruited through an AF clinic to participate in individual interviews prior to the cardioversion and at 6 and 12 weeks post procedure. Pre-cardioversion, older adults experienced symptom and health care-related stressors superimposed on existing non-AF stressors. They used a range of emotion and problem-focused coping. Non-AF stressors increased post procedure at the same time that participants perceived less need for coping strategies with a return to regular rhythm. There was a shift from AF to non-AF related stressors following the cardioversion but a decrease in coping strategies. Older adults with AF should be encouraged to maintain use of coping strategies to manage ongoing stress and reduce the risk of AF recurrence.

  14. The Directly Observed Therapy Short-Course (DOTS strategy in Samara Oblast, Russian Federation

    Directory of Open Access Journals (Sweden)

    Nikolayevskyy V

    2006-03-01

    Full Text Available Abstract Background The World Health Organisation (WHO defines Russia as one of the 22 highest-burden countries for tuberculosis (TB. The WHO Directly Observed Treatment Short Course (DOTS strategy employing a standardised treatment for 6 months produces the highest cure rates for drug sensitive TB. The Russian TB service traditionally employed individualised treatment. The purpose of this study was to implement a DOTS programme in the civilian and prison sectors of Samara Region of Russia, describe the clinical features and outcomes of recruited patients, determine the proportion of individuals in the cohorts who were infected with drug resistant TB, the degree to which resistance was attributed to the Beijing TB strain family and establish risk factors for drug resistance. Methods prospective study Results 2,099 patients were recruited overall. Treatment outcomes were analysed for patients recruited up to the third quarter of 2003 (n = 920. 75.3% of patients were successfully treated. Unsuccessful outcomes occurred in 7.3% of cases; 3.6% of patients died during treatment, with a significantly higher proportion of smear-positive cases dying compared to smear-negative cases. 14.0% were lost and transferred out. A high proportion of new cases (948 sequential culture-proven TB cases had tuberculosis that was resistant to first-line drugs; (24.9% isoniazid resistant; 20.3% rifampicin resistant; 17.3% multidrug resistant tuberculosis. Molecular epidemiological analysis demonstrated that half of all isolated strains (50.7%; 375/740 belonged to the Beijing family. Drug resistance including MDR TB was strongly associated with infection with the Beijing strain (for MDR TB, 35.2% in Beijing strains versus 9.5% in non-Beijing strains, OR-5.2. Risk factors for multidrug resistant tuberculosis were: being a prisoner (OR 4.4, having a relapse of tuberculosis (OR 3.5, being infected with a Beijing family TB strain (OR 6.5 and having an unsuccessful outcome

  15. Multi-omics Analysis Sheds Light on the Evolution and the Intracellular Lifestyle Strategies of Spotted Fever Group Rickettsia spp.

    Directory of Open Access Journals (Sweden)

    Khalid El Karkouri

    2017-07-01

    Full Text Available Arthropod-borne Rickettsia species are obligate intracellular bacteria which are pathogenic for humans. Within this genus, Rickettsia slovaca and Rickettsia conorii cause frequent and potentially severe infections, whereas Rickettsia raoultii and Rickettsia massiliae cause rare and milder infections. All four species belong to spotted fever group (SFG rickettsiae. However, R. slovaca and R. raoultii cause scalp eschar and neck lymphadenopathy (SENLAT and are mainly associated with Dermacentor ticks, whereas the other two species cause Mediterranean spotted fever (MSF and are mainly transmitted by Rhipicephalus ticks. To identify the potential genes and protein profiles and to understand the evolutionary processes that could, comprehensively, relate to the differences in virulence and pathogenicity observed between these four species, we compared their genomes and proteomes. The virulent and milder agents displayed divergent phylogenomic evolution in two major clades, whereas either SENLAT or MSF disease suggests a discrete convergent evolution of one virulent and one milder agent, despite their distant genetic relatedness. Moreover, the two virulent species underwent strong reductive genomic evolution and protein structural variations, as well as a probable loss of plasmid(s, compared to the two milder species. However, an abundance of mobilome genes was observed only in the less pathogenic species. After infecting Xenopus laevis cells, the virulent agents displayed less up-regulated than down-regulated proteins, as well as less number of identified core proteins. Furthermore, their similar and distinct protein profiles did not contain some genes (e.g., ompA/B and rickA known to be related to rickettsial adhesion, motility and/or virulence, but may include other putative virulence-, antivirulence-, and/or disease-related proteins. The identified evolutionary forces herein may have a strong impact on intracellular expressions and strategies in

  16. Multi-omics Analysis Sheds Light on the Evolution and the Intracellular Lifestyle Strategies of Spotted Fever Group Rickettsia spp.

    Science.gov (United States)

    El Karkouri, Khalid; Kowalczewska, Malgorzata; Armstrong, Nicholas; Azza, Said; Fournier, Pierre-Edouard; Raoult, Didier

    2017-01-01

    Arthropod-borne Rickettsia species are obligate intracellular bacteria which are pathogenic for humans. Within this genus, Rickettsia slovaca and Rickettsia conorii cause frequent and potentially severe infections, whereas Rickettsia raoultii and Rickettsia massiliae cause rare and milder infections. All four species belong to spotted fever group (SFG) rickettsiae. However, R. slovaca and R. raoultii cause scalp eschar and neck lymphadenopathy (SENLAT) and are mainly associated with Dermacentor ticks, whereas the other two species cause Mediterranean spotted fever (MSF) and are mainly transmitted by Rhipicephalus ticks. To identify the potential genes and protein profiles and to understand the evolutionary processes that could, comprehensively, relate to the differences in virulence and pathogenicity observed between these four species, we compared their genomes and proteomes. The virulent and milder agents displayed divergent phylogenomic evolution in two major clades, whereas either SENLAT or MSF disease suggests a discrete convergent evolution of one virulent and one milder agent, despite their distant genetic relatedness. Moreover, the two virulent species underwent strong reductive genomic evolution and protein structural variations, as well as a probable loss of plasmid(s), compared to the two milder species. However, an abundance of mobilome genes was observed only in the less pathogenic species. After infecting Xenopus laevis cells, the virulent agents displayed less up-regulated than down-regulated proteins, as well as less number of identified core proteins. Furthermore, their similar and distinct protein profiles did not contain some genes (e.g., ompA/B and rickA) known to be related to rickettsial adhesion, motility and/or virulence, but may include other putative virulence-, antivirulence-, and/or disease-related proteins. The identified evolutionary forces herein may have a strong impact on intracellular expressions and strategies in these rickettsiae

  17. Improving energy efficiency: Strategies for supporting sustained market evolution in developing and transitioning countries

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, S.

    1998-02-01

    This report presents a framework for considering market-oriented strategies for improving energy efficiency that recognize the conditions of developing and transitioning countries, and the need to strengthen the effectiveness of market forces in delivering greater energy efficiency. It discusses policies that build markets in general, such as economic and energy pricing reforms that encourage competition and increase incentives for market actors to improve the efficiency of their energy use, and measures that reduce the barriers to energy efficiency in specific markets such that improvement evolves in a dynamic, lasting manner. The report emphasizes how different policies and measures support one another and can create a synergy in which the whole is greater than the sum of the parts. In addressing this topic, it draws on the experience with market transformation energy efficiency programs in the US and other industrialized countries.

  18. The Dynamic Evolution of Firms’ Pollution Control Strategy under Graded Reward-Penalty Mechanism

    Directory of Open Access Journals (Sweden)

    Li Ming Chen

    2016-01-01

    Full Text Available The externality of pollution problem makes firms lack enough incentive to reduce pollution emission. Therefore, it is necessary to design a reasonable environmental regulation mechanism so as to effectively urge firms to control pollution. In order to inspire firms to control pollution, we divide firms into different grades according to their pollution level and construct an evolutionary game model to analyze the interaction between government’s regulation and firms’ pollution control under graded reward-penalty mechanism. Then, we discuss stability of firms’ pollution control strategy and derive the condition of inspiring firms to control pollution. Our findings indicate that firms tend to control pollution after long-term repeated games if government’s excitation level and monitoring frequency meet some conditions. Otherwise, firms tend to discharge pollution that exceeds the stipulated standards. As a result, in order to effectively control pollution, a government should adjust its excitation level and monitoring frequency reasonably.

  19. Evolution of flowering strategies in Oenothera glazioviana: an integral projection model approach.

    Science.gov (United States)

    Rees, Mark; Rose, Karen E

    2002-07-22

    The timing of reproduction is a key determinant of fitness. Here, we develop parameterized integral projection models of size-related flowering for the monocarpic perennial Oenothera glazioviana and use these to predict the evolutionarily stable strategy (ESS) for flowering. For the most part there is excellent agreement between the model predictions and the results of quantitative field studies. However, the model predicts a much steeper relationship between plant size and the probability of flowering than observed in the field, indicating selection for a 'threshold size' flowering function. Elasticity and sensitivity analysis of population growth rate lambda and net reproductive rate R(0) are used to identify the critical traits that determine fitness and control the ESS for flowering. Using the fitted model we calculate the fitness landscape for invading genotypes and show that this is characterized by a ridge of approximately equal fitness. The implications of these results for the maintenance of genetic variation are discussed.

  20. 'Desa SIAGA', the 'Alert Village': the evolution of an iconic brand in Indonesian public health strategies.

    Science.gov (United States)

    Hill, Peter S; Goeman, Lieve; Sofiarini, Rahmi; Djara, Maddi M

    2014-07-01

    In 1999, the Ministry of Women's Empowerment in Indonesia worked with advertisers in Jakarta and international technical advisors to develop the concept of 'Suami SIAGA', the 'Alert Husband', confronting Indonesian males with their responsibilities to be aware of their wives' needs and ensure early access if needed to trained obstetrics care. The model was rapidly expanded to apply to the 'Desa SIAGA', the 'Alert Village', with communities assuming the responsibility for awareness of the risks of pregnancy and childbirth, and supporting registered pregnant mothers with funding and transportation for emergency obstetric assistance, and identified blood donors. Based on the participant observation, interviews and documentary analysis, this article uses a systems perspective to trace the evolution of that iconic 'brand' as new national and international actors further developed the concept and its application in provincial and national programmes. In 2010, it underwent a further transformation to become 'Desa Siaga Aktif', a national programme with responsibilities expanded to include the provision of basic health services at village level, and the surveillance of communicable disease, monitoring of lifestyle activities and disaster preparedness, in addition to the management of obstetric emergencies. By tracking the use of this single 'brand', the study provides insights into the complex adaptive system of policy and programme development with its rich interactions between multiple international, national, provincial and sectoral stakeholders, the unpredictable responses to feedback from these actors and their activities and the resultant emergence of new policy elements, new programmes and new levels of operation within the system. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

  1. Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation

    OpenAIRE

    Vas, Wollis J.; Shah, Mittal; Al Hosni, Rawiya; Owen, Helen C.; Roberts, Scott J.

    2017-01-01

    Complications resulting from impaired fracture healing have major clinical implications on fracture management strategies. Novel concepts taken from developmental biology have driven research strategies towards the elaboration of regenerative approaches that can truly harness the complex cellular events involved in tissue formation and repair. Advances in polymer technology and a better understanding of naturally derived scaffolds have given rise to novel biomaterials with an increasing abili...

  2. Applying neutral drift to the directed molecular evolution of a β-glucuronidase into a β-galactosidase: Two different evolutionary pathways lead to the same variant

    Directory of Open Access Journals (Sweden)

    Hale Jennifer R

    2011-05-01

    Full Text Available Abstract Background Directed protein evolution has been used to modify protein activity and research has been carried out to enhance the production of high quality mutant libraries. Many theoretical approaches suggest that allowing a population to undergo neutral selection may be valuable in directed evolution experiments. Findings Here we report on an investigation into the value of neutral selection in a classical model system for directed evolution, the conversion of the E. coli β-glucuronidase to a β-galactosidase activity. We find that neutral selection, i.e. selection for retaining glucuronidase activity, can efficiently identify the majority of sites of mutation that have been identified as beneficial for galactosidase activity in previous experiments. Each variant demonstrating increased galactosidase activity identified by our neutral drift experiments contained a mutation at one of four sites, T509, S557, N566 or W529. All of these sites have previously been identified using direct selection for beta galactosidase activity. Conclusions Our results are consistent with others that show that a neutral selection approach can be effective in selecting improved variants. However, we interpret our results to show that neutral selection is, in this case, not a more efficient approach than conventional directed evolution approaches. However, the neutral approach is likely to be beneficial when the resulting library can be screened for a range of related activities. More detailed statistical studies to resolve the apparent differences between this system and others are likely to be a fruitful avenue for future research.

  3. Late-life suicide prevention strategies: current status and future directions.

    Science.gov (United States)

    Van Orden, Kim; Deming, Charlene

    2017-09-08

    Late life suicide prevention differs from suicide prevention for other age groups: first, the number of older adults worldwide is on the rise; second, late-life suicide receives much less attention in all societal spheres, from the media, to federal funding agencies, to healthcare initiatives. Recent findings indicate an association between internalized ageist stereotypes and reduced will to live. Recent research also addresses the role of cognitive control as a contributor to risk and as an intervention target (e.g., through psychotherapies such as problem solving therapy) as well as firearm safety as a promising, though a politicized and challenging strategy to implement. Another strategy that may prove feasible is an approach on upstream prevention strategies in healthcare. One strategy we believe holds great promise is the promotion of high quality geriatric medicine. Geriatricians are trained to work with patients to prioritize the promotion of physical and cognitive functioning (rather than solely absence of disease) and to focus on well-being as a goal. Thus, geriatricians routinely target numerous late-life suicide risk factors-physical illness, functioning, pain, and (dis)satisfaction with life. However, efficacious strategies will not prevent suicide deaths if they are not implemented-addressing ageism as a universal prevention strategy is essential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Evolution of transoral approaches, endoscopic endonasal approaches, and reduction strategies for treatment of craniovertebral junction pathology: a treatment algorithm update.

    Science.gov (United States)

    Dlouhy, Brian J; Dahdaleh, Nader S; Menezes, Arnold H

    2015-04-01

    The craniovertebral junction (CVJ), or the craniocervical junction (CCJ) as it is otherwise known, houses the crossroads of the CNS and is composed of the occipital bone that surrounds the foramen magnum, the atlas vertebrae, the axis vertebrae, and their associated ligaments and musculature. The musculoskeletal organization of the CVJ is unique and complex, resulting in a wide range of congenital, developmental, and acquired pathology. The refinements of the transoral approach to the CVJ by the senior author (A.H.M.) in the late 1970s revolutionized the treatment of CVJ pathology. At the same time, a physiological approach to CVJ management was adopted at the University of Iowa Hospitals and Clinics in 1977 based on the stability and motion dynamics of the CVJ and the site of encroachment, incorporating the transoral approach for irreducible ventral CVJ pathology. Since then, approaches and techniques to treat ventral CVJ lesions have evolved. In the last 40 years at University of Iowa Hospitals and Clinics, multiple approaches to the CVJ have evolved and a better understanding of CVJ pathology has been established. In addition, new reduction strategies that have diminished the need to perform ventral decompressive approaches have been developed and implemented. In this era of surgical subspecialization, to properly treat complex CVJ pathology, the CVJ specialist must be trained in skull base transoral and endoscopic endonasal approaches, pediatric and adult CVJ spine surgery, and must understand and be able to treat the complex CSF dynamics present in CVJ pathology to provide the appropriate, optimal, and tailored treatment strategy for each individual patient, both child and adult. This is a comprehensive review of the history and evolution of the transoral approaches, extended transoral approaches, endoscopie assisted transoral approaches, endoscopie endonasal approaches, and CVJ reduction strategies. Incorporating these advancements, the authors update the

  5. Evolution of ITER tritium confinement strategy and adaptation to Cadrache site conditions and French regulatory requirements

    International Nuclear Information System (INIS)

    Murdoch, D.

    2007-01-01

    The ITER Nuclear Buildings include the Tokamak, Tritium and Diagnostic Buildings (Tokamak Complex) and the Hot Cell and Low Level Radioactive Waste Buildings. The Tritium Confinement Strategy of the Nuclear Buildings comprises key features of the Atmosphere and Vent Detritiation Systems (ADS/VDS) and the Heating, Ventilation and Air Conditioning (HVAC) Systems. The designs developed during the ITER EDA (Engineering Design Activities) for these systems need to be adapted to the specific conditions of the Cadarache site and modified to conform with the regulatory requirements applicable to Installations Nucleaires de Base (INB) - Basic Nuclear Installations - in France. The highest priority for such adaptation has been identified as the Tritium Confinement of the Tokamak Complex and the progress in development of a robust, coherent design concept compliant with French practice is described in the paper. The Tokamak Complex HVAC concept for generic conditions was developed for operational cost minimisation under more extreme climatic conditions (primarily temperature) than those valid for Cadarache, and incorporated recirculation of a large fraction of the air flow through the HVAC systems to achieve this objective. Due to the impracticality of precluding the spread of contamination from areas of higher activity to less contaminated areas, this concept has been abandoned in favour of a once-through configuration, which requires a complete redesign, with revised air change rates, module sizes, layout, redundancy provisions and other features. The ADS/VDS concept developed for the generic design of the ITER Tokamak Complex is undergoing a radical revision in which the system architecture, module sizing and basic process are being optimised for the Cadarache conditions. Investigation is being launched into the implementation of a wet stripper concept to replace the molecular sieve (MS) beds incorporated in the generic design, where concerns have been raised over low

  6. Crystal and Particle Engineering Strategies for Improving Powder Compression and Flow Properties to Enable Continuous Tablet Manufacturing by Direct Compression.

    Science.gov (United States)

    Chattoraj, Sayantan; Sun, Changquan Calvin

    2018-04-01

    Continuous manufacturing of tablets has many advantages, including batch size flexibility, demand-adaptive scale up or scale down, consistent product quality, small operational foot print, and increased manufacturing efficiency. Simplicity makes direct compression the most suitable process for continuous tablet manufacturing. However, deficiencies in powder flow and compression of active pharmaceutical ingredients (APIs) limit the range of drug loading that can routinely be considered for direct compression. For the widespread adoption of continuous direct compression, effective API engineering strategies to address power flow and compression problems are needed. Appropriate implementation of these strategies would facilitate the design of high-quality robust drug products, as stipulated by the Quality-by-Design framework. Here, several crystal and particle engineering strategies for improving powder flow and compression properties are summarized. The focus is on the underlying materials science, which is the foundation for effective API engineering to enable successful continuous manufacturing by the direct compression process. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. LIFETIME AND SPECTRAL EVOLUTION OF A MAGMA OCEAN WITH A STEAM ATMOSPHERE: ITS DETECTABILITY BY FUTURE DIRECT IMAGING

    Energy Technology Data Exchange (ETDEWEB)

    Hamano, Keiko; Kawahara, Hajime; Abe, Yutaka [Department of Earth and Planetary Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Onishi, Masanori [Department of Earth and Planetary Sciences, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Hashimoto, George L., E-mail: keiko@eps.s.u-tokyo.ac.jp [Department of Earth Sciences, Okayama University, 3-1-1 Tsushima-Naka, Kita, Okayama, 700-8530 (Japan)

    2015-06-20

    We present the thermal evolution and emergent spectra of solidifying terrestrial planets along with the formation of steam atmospheres. The lifetime of a magma ocean and its spectra through a steam atmosphere depends on the orbital distance of the planet from the host star. For a Type I planet, which is formed beyond a certain critical distance from the host star, the thermal emission declines on a timescale shorter than approximately 10{sup 6} years. Therefore, young stars should be targets when searching for molten planets in this orbital region. In contrast, a Type II planet, which is formed inside the critical distance, will emit significant thermal radiation from near-infrared atmospheric windows during the entire lifetime of the magma ocean. The K{sub s} and L bands will be favorable for future direct imaging because the planet-to-star contrasts of these bands are higher than approximately 10{sup −7}–10{sup −8}. Our model predicts that, in the Type II orbital region, molten planets would be present over the main sequence of the G-type host star if the initial bulk content of water exceeds approximately 1 wt%. In visible atmospheric windows, the contrasts of the thermal emission drop below 10{sup −10} in less than 10{sup 5} years, whereas those of the reflected light remain 10{sup −10} for both types of planets. Since the contrast level is comparable to those of reflected light from Earth-sized planets in the habitable zone, the visible reflected light from molten planets also provides a promising target for direct imaging with future ground- and space-based telescopes.

  8. Directed Evolution of Recombinant C-Terminal Truncated Staphylococcus epidermidis Lipase AT2 for the Enhancement of Thermostability

    Directory of Open Access Journals (Sweden)

    Jiivittha Veno

    2017-11-01

    Full Text Available In the industrial processes, lipases are expected to operate at temperatures above 45 °C and could retain activity in organic solvents. Hence, a C-terminal truncated lipase from Staphylococcus epidermis AT2 (rT-M386 was engineered by directed evolution. A mutant with glycine-to-cysteine substitution (G210C demonstrated a remarkable improvement of thermostability, whereby the mutation enhanced the activity five-fold when compared to the rT-M386 at 50 °C. The rT-M386 and G210C lipases were purified concurrently using GST-affinity chromatography. The biochemical and biophysical properties of both enzymes were investigated. The G210C lipase showed a higher optimum temperature (45 °C and displayed a more prolonged half-life in the range of 40–60 °C as compared to rT-M386. Both lipases exhibited optimal activity and stability at pH 8. The G210C showed the highest stability in the presence of polar organic solvents at 50 °C compared to the rT-M386. Denatured protein analysis presented a significant change in the molecular ellipticity value above 60 °C, which verified the experimental result on the temperature and thermostability profile of G210C.

  9. Three dimensional modelling of grain boundary interaction and evolution during directional solidification of multi-crystalline silicon

    Science.gov (United States)

    Jain, T.; Lin, H. K.; Lan, C. W.

    2018-03-01

    The development of grain structures during directional solidification of multi-crystalline silicon (mc-Si) plays a crucial role in the materials quality for silicon solar cells. Three dimensional (3D) modelling of the grain boundary (GB) interaction and evolution based on phase fields by considering anisotropic GB energy and mobility for mc-Si is carried out for the first time to elucidate the process. The energy and mobility of GBs are allowed to depend on misorientation and the GB plane. To examine the correctness of our method, the known the coincident site lattice (CSL) combinations such as (∑ a + ∑ b → ∑ a × b) or (∑ a + ∑ b → ∑ a / b) are verified. We frther discuss how to use the GB normal to characterize a ∑ 3 twin GB into a tilt or a twist one, and show the interaction between tilt and twist ∑ 3 twin GBs. Two experimental scenarios are considered for comparison and the results are in good agreement with the experiments as well as the theoretical predictions.

  10. MoS2 nanosheets direct supported on reduced graphene oxide: An advanced electrocatalyst for hydrogen evolution reaction.

    Directory of Open Access Journals (Sweden)

    Jiamu Cao

    Full Text Available Molybdenum disulfide nanosheets/reduced graphene oxide (MoS2 NSs/rGO nanohybrid as a highly effective catalyst for hydrogen evolution reaction (HER have been successfully synthesized by a facile microwave-assisted method. The results clearly reveal that direct grown of MoS2 NSs on rGO have been achieved. Electrochemical tests show that the as-prepared hybrid material exhibited excellent HER activity, with a small Tafel slope of 57 mV dec-1, an overpotential of 130 mV and remarkable cycling stability. After analysis, the observed outstanding catalytic performance can be attributed to the uniform distribution of the MoS2 NSs, which are characterized by the presence of multiple active sites as well as the effective electron transport route provided by the conductive rGO substrate. Moreover, according to the classic theory, the mechanism governing of the catalytic HER on the MoS2 NSs/rGO nanohybrid has been clarified.

  11. Directed evolution of toluene dioxygenase from Pseudomonas putida for improved selectivity toward cis-indandiol during indene bioconversion.

    Science.gov (United States)

    Zhang, N; Stewart, B G; Moore, J C; Greasham, R L; Robinson, D K; Buckland, B C; Lee, C

    2000-10-01

    Toluene dioxygenase (TDO) from Pseudomonas putida F1 converts indene to a mixture of cis-indandiol (racemic), 1-indenol, and 1-indanone. The desired product, cis-(1S,2R)-indandiol, is a potential key intermediate in the chemical synthesis of indinavir sulfate (Crixivan), Merck's HIV-1 protease inhibitor for the treatment of AIDS. To reduce the undesirable byproducts 1-indenol and 1-indanone formed during indene bioconversion, the recombinant TDO expressed in Escherichia coli was evolved by directed evolution using the error-prone polymerase chain reaction (epPCR) method. High-throughput fluorometric and spectrophotometric assays were developed for rapid screening of the mutant libraries in a 96-well format. Mutants with reduced 1-indenol by-product formation were identified, and the individual indene bioconversion product profiles of the selected mutants were confirmed by HPLC. Changes in the amino acid sequence of the mutant enzymes were identified by analyzing the nucleotide sequence of the genes. A mutant with the most desirable product profile from each library, defined as the most reduced 1-indenol concentration and with the highest cis-(1S,2R)-indandiol enantiomeric excess, was used to perform each subsequent round of mutagenesis. After three rounds of mutagenesis and screening, mutant 1C4-3G was identified to have a threefold reduction in 1-indenol formation over the wild type (20% vs 60% of total products) and a 40% increase of product (cis-indandiol) yield.

  12. Oil Exploration and Production in Africa since 2014. Evolution of the Key Players and their Strategies

    International Nuclear Information System (INIS)

    Auge, Benjamin

    2018-05-01

    The fall in oil prices, which began in fall 2014, had a significant influence on the strategies of the key players in the oil industry in Africa. The continent's oil sector has experienced deep-reaching changes, ranging from a drop in exploration budgets, the disappearance or sale of weakened companies, the reorganization or pullback of the traditional oil majors, the establishment of new companies and the arrival of state-owned companies attracted by the crisis-induced windfall effects. Yet the crisis has not redefined the geography of African production, whose principal giants are and will continue to be Nigeria, Angola, Algeria and Libya, at least in terms of reserves. Nevertheless, new zones have emerged, in particular due to the risks taken by junior players backed by powerful investment funds that have had faith in the potential of geologists and technical teams formerly employed by the big companies. This is first of all the case in East Africa, for oil, in Uganda and Kenya, along with gas, with Tanzania and Mozambique. Several very significant oil and gas discoveries have been made in a new basin located between Mauritania and Guinea, contributing to its development. However, no single African model has taken shape, as each company has followed its own path in making decisions about acquisition and exploration. Whereas traditional players, such as the Western majors ENI and Total, have continued to invest on this continent that plays a central role in their global production and strategy, some big companies, such as ConocoPhilipps, have quite simply left the field, while others, such as BP and ExxonMobil, have made new high-risk acquisitions. As for the large Asian state-owned companies, China's investments in exploration and production have tended to stagnate (concerning CNPC and Sinopec in particular), while others, such as the Indonesian Pertamina or India's ONGC, have significantly bolstered their presence. The disengagement of the

  13. Evolution of risk assessment strategies for food and feed uses of stacked GM events.

    Science.gov (United States)

    Kramer, Catherine; Brune, Phil; McDonald, Justin; Nesbitt, Monique; Sauve, Alaina; Storck-Weyhermueller, Sabine

    2016-09-01

    Data requirements are not harmonized globally for the regulation of food and feed derived from stacked genetically modified (GM) events, produced by combining individual GM events through conventional breeding. The data required by some regulatory agencies have increased despite the absence of substantiated adverse effects to animals or humans from the consumption of GM crops. Data from studies conducted over a 15-year period for several stacked GM event maize (Zea mays L.) products (Bt11 ×  GA21, Bt11 ×  MIR604, MIR604 ×  GA21, Bt11 ×  MIR604 ×  GA21, Bt11 ×  MIR162 ×  GA21 and Bt11 ×  MIR604 ×  MIR162 ×  GA21), together with their component single events, are presented. These data provide evidence that no substantial changes in composition, protein expression or insert stability have occurred after combining the single events through conventional breeding. An alternative food and feed risk assessment strategy for stacked GM events is suggested based on a problem formulation approach that utilizes (i) the outcome of the single event risk assessments, and (ii) the potential for interactions in the stack, based on an understanding of the mode of action of the transgenes and their products. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals.

    Science.gov (United States)

    Sunagar, Kartik; Moran, Yehu

    2015-10-01

    Animal venoms are theorized to evolve under the significant influence of positive Darwinian selection in a chemical arms race scenario, where the evolution of venom resistance in prey and the invention of potent venom in the secreting animal exert reciprocal selection pressures. Venom research to date has mainly focused on evolutionarily younger lineages, such as snakes and cone snails, while mostly neglecting ancient clades (e.g., cnidarians, coleoids, spiders and centipedes). By examining genome, venom-gland transcriptome and sequences from the public repositories, we report the molecular evolutionary regimes of several centipede and spider toxin families, which surprisingly accumulated low-levels of sequence variations, despite their long evolutionary histories. Molecular evolutionary assessment of over 3500 nucleotide sequences from 85 toxin families spanning the breadth of the animal kingdom has unraveled a contrasting evolutionary strategy employed by ancient and evolutionarily young clades. We show that the venoms of ancient lineages remarkably evolve under the heavy constraints of negative selection, while toxin families in lineages that originated relatively recently rapidly diversify under the influence of positive selection. We propose that animal venoms mostly employ a 'two-speed' mode of evolution, where the major influence of diversifying selection accompanies the earlier stages of ecological specialization (e.g., diet and range expansion) in the evolutionary history of the species-the period of expansion, resulting in the rapid diversification of the venom arsenal, followed by longer periods of purifying selection that preserve the potent toxin pharmacopeia-the period of purification and fixation. However, species in the period of purification may re-enter the period of expansion upon experiencing a major shift in ecology or environment. Thus, we highlight for the first time the significant roles of purifying and episodic selections in shaping animal

  15. The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals.

    Directory of Open Access Journals (Sweden)

    Kartik Sunagar

    2015-10-01

    Full Text Available Animal venoms are theorized to evolve under the significant influence of positive Darwinian selection in a chemical arms race scenario, where the evolution of venom resistance in prey and the invention of potent venom in the secreting animal exert reciprocal selection pressures. Venom research to date has mainly focused on evolutionarily younger lineages, such as snakes and cone snails, while mostly neglecting ancient clades (e.g., cnidarians, coleoids, spiders and centipedes. By examining genome, venom-gland transcriptome and sequences from the public repositories, we report the molecular evolutionary regimes of several centipede and spider toxin families, which surprisingly accumulated low-levels of sequence variations, despite their long evolutionary histories. Molecular evolutionary assessment of over 3500 nucleotide sequences from 85 toxin families spanning the breadth of the animal kingdom has unraveled a contrasting evolutionary strategy employed by ancient and evolutionarily young clades. We show that the venoms of ancient lineages remarkably evolve under the heavy constraints of negative selection, while toxin families in lineages that originated relatively recently rapidly diversify under the influence of positive selection. We propose that animal venoms mostly employ a 'two-speed' mode of evolution, where the major influence of diversifying selection accompanies the earlier stages of ecological specialization (e.g., diet and range expansion in the evolutionary history of the species-the period of expansion, resulting in the rapid diversification of the venom arsenal, followed by longer periods of purifying selection that preserve the potent toxin pharmacopeia-the period of purification and fixation. However, species in the period of purification may re-enter the period of expansion upon experiencing a major shift in ecology or environment. Thus, we highlight for the first time the significant roles of purifying and episodic selections

  16. The politics and strategy of industry self-regulation: the pharmaceutical industry's principles for ethical direct-to-consumer advertising as a deceptive blocking strategy.

    Science.gov (United States)

    Arnold, Denis G; Oakley, James L

    2013-06-01

    As the pharmaceutical industry lobbies European regulators to permit direct-to-consumer advertising (DTCA) of prescription drugs in the European Union, we found that five leading companies violated industry-developed and -promulgated standards for ethical advertising in the United States. Utilizing multiple data sources and methods, we demonstrate a consistent failure by companies that market erectile dysfunction drugs to comply with the industry's guiding principles for ethical DTCA over a four-year period despite pledges of compliance by company leaders. Noncompliance resulted in children being exposed to sexually themed promotional messages more than 100 billion times. We argue that the guidelines are a coordinated effort by the industry to prevent unwanted federal regulation, and we introduce the concept of a blocking strategy to explain company behavior and to advance theoretical understanding of firms' public affairs strategies. We recommend policy responses to prevent deceptive practices, protect children from adult content, and promote genuine health care education.

  17. Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India

    Directory of Open Access Journals (Sweden)

    Abhijeet Ganapule

    2017-12-01

    Full Text Available Purpose: There are limited data from developing countries on the role and cost-effectiveness of allogeneic stem cell transplantation (allo-SCT for patients with acute myeloid leukemia (AML. Patients and Methods: We undertook a retrospective descriptive study of all patients with AML who underwent allo-SCT from 1994 to 2013 at our center to evaluate the clinical outcomes and cost-effectiveness of this therapeutic modality. Results: Two hundred fifty-four consecutive patients, median age 34 years, who underwent allo-SCT at our center were included in this study. There were 161 males (63.4%. The 5-year overall survival (OS and event-free survival for the entire cohort was 40.1 ± 3.5% and 38.7 ± 3.4%, respectively. The 5-year OS for patients in first (CR1, second, and third complete remission and with disease/refractory AML was 53.1 ± 5.2%, 48.2 ± 8.3%, 31.2 ± 17.8%, and 16.0 ± 4.4%, respectively (P < .001. From 2007, reduced intensity conditioning (RIC with fludarabine and melphalan (Flu/Mel was used in a majority of patients in CR1 (n = 67. Clinical outcomes were compared with historical conventional myeloablative conditioning regimens (n = 38. Use of Flu/Mel was associated with lower treatment-related mortality at 1 year, higher incidence of chronic graft-versus-host-disease, and comparable relapse rates. The 5-year OS and event-free survival for Flu/Mel and myeloablative conditioning group was 67.2 ± 6.6% versus 38.1 ± 8.1% (P = .003 and 63.8 ± 6.4% versus 32.3 ± 7.9% (P = .002, respectively. Preliminary cost analysis suggests that in our medical cost payment system, RIC allo-SCT in CR1 was likely the most cost-effective strategy in the management of AML. Conclusion: In a resource-constrained environment, Flu/Mel RIC allo-SCT for AML CR1 is likely the most efficacious and cost-effective approach in a subset of newly diagnosed young adult patients.

  18. Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

    Science.gov (United States)

    Xu, Jian-zhong; Zhang, Wei-guo

    2016-01-01

    With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

  19. Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

    Science.gov (United States)

    Sherrill, Joel T

    2016-01-01

    This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

  20. Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance▿†

    Science.gov (United States)

    Baquero, Fernando; Coque, Teresa M.; de la Cruz, Fernando

    2011-01-01

    In recent years, the explosive spread of antibiotic resistance determinants among pathogenic, commensal, and environmental bacteria has reached a global dimension. Classical measures trying to contain or slow locally the progress of antibiotic resistance in patients on the basis of better antibiotic prescribing policies have clearly become insufficient at the global level. Urgent measures are needed to directly confront the processes influencing antibiotic resistance pollution in the microbiosphere. Recent interdisciplinary research indicates that new eco-evo drugs and strategies, which take ecology and evolution into account, have a promising role in resistance prevention, decontamination, and the eventual restoration of antibiotic susceptibility. This minireview summarizes what is known and what should be further investigated to find drugs and strategies aiming to counteract the “four P's,” penetration, promiscuity, plasticity, and persistence of rapidly spreading bacterial clones, mobile genetic elements, or resistance genes. The term “drug” is used in this eco-evo perspective as a tool to fight resistance that is able to prevent, cure, or decrease potential damage caused by antibiotic resistance, not necessarily only at the individual level (the patient) but also at the ecological and evolutionary levels. This view offers a wealth of research opportunities for science and technology and also represents a large adaptive challenge for regulatory agencies and public health officers. Eco-evo drugs and interventions constitute a new avenue for research that might influence not only antibiotic resistance but the maintenance of a healthy interaction between humans and microbial systems in a rapidly changing biosphere. PMID:21576439

  1. Combined use of leaf size and economics traits allows direct comparison of hydrophyte and terrestrial herbaceous adaptive strategies.

    Science.gov (United States)

    Pierce, Simon; Brusa, Guido; Sartori, Matteo; Cerabolini, Bruno E L

    2012-04-01

    Hydrophytes generally exhibit highly acquisitive leaf economics. However, a range of growth forms is evident, from small, free-floating and rapidly growing Lemniden to large, broad-leaved Nymphaeiden, denoting variability in adaptive strategies. Traits used to classify adaptive strategies in terrestrial species, such as canopy height, are not applicable to hydrophytes. We hypothesize that hydrophyte leaf size traits and economics exhibit sufficient overlap with terrestrial species to allow a common classification of plant functional types, sensu Grime's CSR theory. Leaf morpho-functional traits were measured for 61 species from 47 water bodies in lowland continental, sub-alpine and alpine bioclimatic zones in southern Europe and compared against the full leaf economics spectrum and leaf size range of terrestrial herbs, and between hydrophyte growth forms. Hydrophytes differed in the ranges and mean values of traits compared with herbs, but principal components analysis (PCA) demonstrated that both groups shared axes of trait variability: PCA1 encompassed size variation (area and mass), and PCA2 ranged from relatively dense, carbon-rich leaves to nitrogen-rich leaves of high specific leaf area (SLA). Most growth forms exhibited trait syndromes directly equivalent to herbs classified as R adapted, although Nymphaeiden ranged between C and SR adaptation. Our findings support the hypothesis that hydrophyte adaptive strategy variation reflects fundamental trade-offs in economics and size that govern all plants, and that hydrophyte adaptive strategies can be directly compared with terrestrial species by combining leaf economics and size traits.

  2. Research of expansion strategy of Postal Direct Mail in Anhui Province, China

    OpenAIRE

    Sun, Zhengxi

    2012-01-01

    DM is “direct mail “, which is generally translated from English, abbreviated as DM. It means the multiform advertisements with the given information that are delivered to the target groups (potential customer, individuals and enterprises) directly by mailing service. DM is ranked a third media abroad following TV network and newspaper. It accounts for 15 - 20 % market share of the advertising market. However, in China, DM only accounts for less than 3 % market share at present, therefor...

  3. Evaluation and Future Direction of Intellectual Property Strategy - Setting out a new intellectual property policy - (Japanese)

    OpenAIRE

    KUGAI Takashi

    2010-01-01

    1. An intellectual property strategy is a policy aimed at improving the international competitiveness of industry and reinvigorating the economy through the creation, protection, and greater use of intellectual property. 2. The realization of IP policies conventionally considered difficult to implement and greater awareness of intellectual property at all levels of society, as demonstrated the establishment of Intellectual Property High Courts that exclusively and solely handle intellectual p...

  4. Network analysis to detect common strategies in Italian foreign direct investment

    Science.gov (United States)

    De Masi, G.; Giovannetti, G.; Ricchiuti, G.

    2013-03-01

    In this paper we reconstruct and discuss the network of Italian firms investing abroad, exploiting information from complex network analysis. This method, detecting the key nodes of the system (both in terms of firms and countries of destination), allows us to single out the linkages among firms without ex-ante priors. Moreover, through the examination of affiliates’ economic activity, it allows us to highlight different internationalization strategies of “leaders” in different manufacturing sectors.

  5. Direct Viewing of Dyslexics' Compensatory Strategies in Speech in Noise Using Auditory Classification Images.

    Science.gov (United States)

    Varnet, Léo; Meunier, Fanny; Trollé, Gwendoline; Hoen, Michel

    2016-01-01

    A vast majority of dyslexic children exhibit a phonological deficit, particularly noticeable in phonemic identification or discrimination tasks. The gap in performance between dyslexic and normotypical listeners appears to decrease into adulthood, suggesting that some individuals with dyslexia develop compensatory strategies. Some dyslexic adults however remain impaired in more challenging listening situations such as in the presence of background noise. This paper addresses the question of the compensatory strategies employed, using the recently developed Auditory Classification Image (ACI) methodology. The results of 18 dyslexics taking part in a phoneme categorization task in noise were compared with those of 18 normotypical age-matched controls. By fitting a penalized Generalized Linear Model on the data of each participant, we obtained his/her ACI, a map of the time-frequency regions he/she relied on to perform the task. Even though dyslexics performed significantly less well than controls, we were unable to detect a robust difference between the mean ACIs of the two groups. This is partly due to the considerable heterogeneity in listening strategies among a subgroup of 7 low-performing dyslexics, as confirmed by a complementary analysis. When excluding these participants to restrict our comparison to the 11 dyslexics performing as well as their average-reading peers, we found a significant difference in the F3 onset of the first syllable, and a tendency of difference on the F4 onset, suggesting that these listeners can compensate for their deficit by relying upon additional allophonic cues.

  6. Directed antigen delivery as a vaccine strategy for an intracellular bacterial pathogen

    Science.gov (United States)

    Bouwer, H. G. Archie; Alberti-Segui, Christine; Montfort, Megan J.; Berkowitz, Nathan D.; Higgins, Darren E.

    2006-03-01

    We have developed a vaccine strategy for generating an attenuated strain of an intracellular bacterial pathogen that, after uptake by professional antigen-presenting cells, does not replicate intracellularly and is readily killed. However, after degradation of the vaccine strain within the phagolysosome, target antigens are released into the cytosol for endogenous processing and presentation for stimulation of CD8+ effector T cells. Applying this strategy to the model intracellular pathogen Listeria monocytogenes, we show that an intracellular replication-deficient vaccine strain is cleared rapidly in normal and immunocompromised animals, yet antigen-specific CD8+ effector T cells are stimulated after immunization. Furthermore, animals immunized with the intracellular replication-deficient vaccine strain are resistant to lethal challenge with a virulent WT strain of L. monocytogenes. These studies suggest a general strategy for developing safe and effective, attenuated intracellular replication-deficient vaccine strains for stimulation of protective immune responses against intracellular bacterial pathogens. CD8+ T cell | replication-deficient | Listeria monocytogenes

  7. Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment.

    Science.gov (United States)

    Khan, M A; Walley, J D; Witter, S N; Imran, A; Safdar, N

    2002-06-01

    An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the

  8. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  9. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  10. Improved security detection strategy in quantum secure direct communication protocol based on four-particle Green-Horne-Zeilinger state

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jian; Nie, Jin-Rui; Li, Rui-Fan [Beijing Univ. of Posts and Telecommunications, Beijing (China). School of Computer; Jing, Bo [Beijing Univ. of Posts and Telecommunications, Beijing (China). School of Computer; Beijing Institute of Applied Meteorology, Beijing (China). Dept. of Computer Science

    2012-06-15

    To enhance the efficiency of eavesdropping detection in the quantum secure direct communication protocol, an improved quantum secure direct communication protocol based on a four-particle Green-Horne-Zeilinger (GHZ) state is presented. In the protocol, the four-particle GHZ state is used to detect eavesdroppers, and quantum dense coding is used to encode the message. In the security analysis, the method of entropy theory is introduced, and two detection strategies are compared quantitatively by using the constraint between the information that the eavesdroppers can obtain and the interference that has been introduced. If the eavesdropper wants to obtain all the information, the detection rate of the quantum secure direct communication using an Einstein-Podolsky-Rosen (EPR) pair block will be 50% and the detection rate of the presented protocol will be 87%. At last, the security of the proposed protocol is discussed. The analysis results indicate that the protocol proposed is more secure than the others. (orig.)

  11. Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

    Science.gov (United States)

    Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

    2015-01-14

    Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

  12. Contemporary Directions in Theories and Psychotherapeutic Strategies in Treatment of Personality Disorders

    DEFF Research Database (Denmark)

    Simonsen, Sebastian; Simonsen, Erik

    2014-01-01

    and improved adaptation. Based on this finding, we argue that the Level of Personality Functioning could be a useful assessment method for improving treatment selection. Finally, we raise questions and offer considerations regarding the understanding of empathy, low motivation and autobiographical memory......In this commentary on treatment strategies for personality disorders, we analyze each of the cases and the problem of low motivation in terms of how they fit with the Level of Personality Functioning scale. We then show how patients vary in terms of both level and breadth of pathology. Three...

  13. Neprilysin inhibition: a brief review of past pharmacological strategies for heart failure treatment and future directions

    Science.gov (United States)

    Howell, Erik H.; Cameron, Scott J.

    2016-01-01

    Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality. PMID:27665860

  14. The evolution of peer review as a basis for scientific publication: directional selection towards a robust discipline?

    Science.gov (United States)

    Ferreira, Catarina; Bastille-Rousseau, Guillaume; Bennett, Amanda M; Ellington, E Hance; Terwissen, Christine; Austin, Cayla; Borlestean, Adrian; Boudreau, Melanie R; Chan, Kevin; Forsythe, Adrian; Hossie, Thomas J; Landolt, Kristen; Longhi, Jessica; Otis, Josée-Anne; Peers, Michael J L; Rae, Jason; Seguin, Jacob; Watt, Cristen; Wehtje, Morgan; Murray, Dennis L

    2016-08-01

    Peer review is pivotal to science and academia, as it represents a widely accepted strategy for ensuring quality control in scientific research. Yet, the peer-review system is poorly adapted to recent changes in the discipline and current societal needs. We provide historical context for the cultural lag that governs peer review that has eventually led to the system's current structural weaknesses (voluntary review, unstandardized review criteria, decentralized process). We argue that some current attempts to upgrade or otherwise modify the peer-review system are merely sticking-plaster solutions to these fundamental flaws, and therefore are unlikely to resolve them in the long term. We claim that for peer review to be relevant, effective, and contemporary with today's publishing demands across scientific disciplines, its main components need to be redesigned. We propose directional changes that are likely to improve the quality, rigour, and timeliness of peer review, and thereby ensure that this critical process serves the community it was created for. © 2015 Cambridge Philosophical Society.

  15. Phylogeny and evolution of life-history strategies in the Sycophaginae non-pollinating fig wasps (Hymenoptera, Chalcidoidea

    Directory of Open Access Journals (Sweden)

    Farache Fernando HA

    2011-06-01

    Full Text Available Abstract Background Non-pollinating Sycophaginae (Hymenoptera, Chalcidoidea form small communities within Urostigma and Sycomorus fig trees. The species show differences in galling habits and exhibit apterous, winged or dimorphic males. The large gall inducers oviposit early in syconium development and lay few eggs; the small gall inducers lay more eggs soon after pollination; the ostiolar gall-inducers enter the syconium to oviposit and the cleptoparasites oviposit in galls induced by other fig wasps. The systematics of the group remains unclear and only one phylogeny based on limited sampling has been published to date. Here we present an expanded phylogeny for sycophagine fig wasps including about 1.5 times the number of described species. We sequenced mitochondrial and nuclear markers (4.2 kb on 73 species and 145 individuals and conducted maximum likelihood and Bayesian phylogenetic analyses. We then used this phylogeny to reconstruct the evolution of Sycophaginae life-history strategies and test if the presence of winged males and small brood size may be correlated. Results The resulting trees are well resolved and strongly supported. With the exception of Apocrytophagus, which is paraphyletic with respect to Sycophaga, all genera are monophyletic. The Sycophaginae are divided into three clades: (i Eukoebelea; (ii Pseudidarnes, Anidarnes and Conidarnes and (iii Apocryptophagus, Sycophaga and Idarnes. The ancestral states for galling habits and male morphology remain ambiguous and our reconstructions show that the two traits are evolutionary labile. Conclusions The three main clades could be considered as tribes and we list some morphological characters that define them. The same biologies re-evolved several times independently, which make Sycophaginae an interesting model to test predictions on what factors will canalize the evolution of a particular biology. The ostiolar gall-inducers are the only monophyletic group. In 15 Myr, they

  16. Software-Supported USER Cloning Strategies for Site-Directed Mutagenesis and DNA Assembly

    DEFF Research Database (Denmark)

    Genee, Hans Jasper; Bonde, Mads Tvillinggaard; Bagger, Frederik Otzen

    2015-01-01

    USER cloning is a fast and versatile method for engineering of plasmid DNA. We have developed a user friendly Web server tool that automates the design of optimal PCR primers for several distinct USER cloning-based applications. Our Web server, named AMUSER (Automated DNA Modifications with USER...... cloning), facilitates DNA assembly and introduction of virtually any type of site-directed mutagenesis by designing optimal PCR primers for the desired genetic changes. To demonstrate the utility, we designed primers for a simultaneous two-position site-directed mutagenesis of green fluorescent protein...... (GFP) to yellow fluorescent protein (YFP), which in a single step reaction resulted in a 94% cloning efficiency. AMUSER also supports degenerate nucleotide primers, single insert combinatorial assembly, and flexible parameters for PCR amplification. AMUSER is freely available online at ....

  17. Bipolar Jet Growth and Decline in Hen 3-1341: A Direct Link to Fast Wind and Outburst Evolution

    National Research Council Canada - National Science Library

    Munari, Ulisse; Siviero, A; Henden, A

    2005-01-01

    We report on and investigate the evolution and disappearance in the symbiotic star Hen 3-1341 of collimated bipolar jets, which take the form of symmetrically displaced components of emission lines...

  18. A review of the irradiation evolution of dispersed oxide nanoparticles in the b.c.c. Fe-Cr system: Current understanding and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Wharry, Janelle P., E-mail: jwharry@purdue.edu [Purdue University, 400 Central Drive, West Lafayette, IN 47907 (United States); Swenson, Matthew J.; Yano, Kayla H. [Boise State University, 1910 University Drive, Boise, ID 83725 (United States)

    2017-04-01

    Thus far, a number of studies have investigated the irradiation evolution of oxide nanoparticles in b.c.c. Fe-Cr based oxide dispersion strengthened (ODS) alloys. But given the inconsistent experimental conditions, results have been widely variable and inconclusive. Crystal structure and chemistry changes differ from experiment to experiment, and the total nanoparticle volume fraction has been observed to both increase and decrease. Furthermore, there has not yet been a comprehensive review of the archival literature. In this paper, we summarize the existing studies on nanoparticle irradiation evolution. We note significant observations with respect to oxide nanoparticle crystallinity, composition, size, and number density. We discuss four possible contributing mechanisms for nanoparticle evolution: ballistic dissolution, Ostwald ripening, irradiation-enhanced diffusion, and homogeneous nucleation. Finally, we propose future directions to achieve a more comprehensive understanding of irradiation effects on oxide nanoparticles in ODS alloys.

  19. Seasonality directs contrasting food collection behavior and nutrient regulation strategies in ants.

    Directory of Open Access Journals (Sweden)

    Steven C Cook

    Full Text Available Long-lived animals, including social insects, often display seasonal shifts in foraging behavior. Foraging is ultimately a nutrient consumption exercise, but the effect of seasonality per se on changes in foraging behavior, particularly as it relates to nutrient regulation, is poorly understood. Here, we show that field-collected fire ant colonies, returned to the laboratory and maintained under identical photoperiod, temperature, and humidity regimes, and presented with experimental foods that had different protein (p to carbohydrate (c ratios, practice summer- and fall-specific foraging behaviors with respect to protein-carbohydrate regulation. Summer colonies increased the amount of food collected as the p:c ratio of their food became increasingly imbalanced, but fall colonies collected similar amounts of food regardless of the p:c ratio of their food. Choice experiments revealed that feeding was non-random, and that both fall and summer ants preferred carbohydrate-biased food. However, ants rarely ate all the food they collected, and their cached or discarded food always contained little carbohydrate relative to protein. From a nutrient regulation strategy, ants consumed most of the carbohydrate they collected, but regulated protein consumption to a similar level, regardless of season. We suggest that varied seasonal food collection behaviors and nutrient regulation strategies may be an adaptation that allows long-lived animals to meet current and future nutrient demands when nutrient-rich foods are abundant (e.g. spring and summer, and to conserve energy and be metabolically more efficient when nutritionally balanced foods are less abundant.

  20. Seasonality directs contrasting food collection behavior and nutrient regulation strategies in ants.

    Science.gov (United States)

    Cook, Steven C; Eubanks, Micky D; Gold, Roger E; Behmer, Spencer T

    2011-01-01

    Long-lived animals, including social insects, often display seasonal shifts in foraging behavior. Foraging is ultimately a nutrient consumption exercise, but the effect of seasonality per se on changes in foraging behavior, particularly as it relates to nutrient regulation, is poorly understood. Here, we show that field-collected fire ant colonies, returned to the laboratory and maintained under identical photoperiod, temperature, and humidity regimes, and presented with experimental foods that had different protein (p) to carbohydrate (c) ratios, practice summer- and fall-specific foraging behaviors with respect to protein-carbohydrate regulation. Summer colonies increased the amount of food collected as the p:c ratio of their food became increasingly imbalanced, but fall colonies collected similar amounts of food regardless of the p:c ratio of their food. Choice experiments revealed that feeding was non-random, and that both fall and summer ants preferred carbohydrate-biased food. However, ants rarely ate all the food they collected, and their cached or discarded food always contained little carbohydrate relative to protein. From a nutrient regulation strategy, ants consumed most of the carbohydrate they collected, but regulated protein consumption to a similar level, regardless of season. We suggest that varied seasonal food collection behaviors and nutrient regulation strategies may be an adaptation that allows long-lived animals to meet current and future nutrient demands when nutrient-rich foods are abundant (e.g. spring and summer), and to conserve energy and be metabolically more efficient when nutritionally balanced foods are less abundant.

  1. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    International Nuclear Information System (INIS)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram; Ahmadvand, Davoud

    2014-01-01

    Highlights: • A novel nanobody directed to antigenic regions on VEGF was identified. • Our nanobody was successfully purified. • Our nanobody significantly inhibited VEGF-induced proliferation of HUVECs in a dose dependent manner. - Abstract: Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate

  2. An empirical strategy to detect bacterial transcript structure from directional RNA-seq transcriptome data.

    Science.gov (United States)

    Wang, Yejun; MacKenzie, Keith D; White, Aaron P

    2015-05-07

    As sequencing costs are being lowered continuously, RNA-seq has gradually been adopted as the first choice for comparative transcriptome studies with bacteria. Unlike microarrays, RNA-seq can directly detect cDNA derived from mRNA transcripts at a single nucleotide resolution. Not only does this allow researchers to determine the absolute expression level of genes, but it also conveys information about transcript structure. Few automatic software tools have yet been established to investigate large-scale RNA-seq data for bacterial transcript structure analysis. In this study, 54 directional RNA-seq libraries from Salmonella serovar Typhimurium (S. Typhimurium) 14028s were examined for potential relationships between read mapping patterns and transcript structure. We developed an empirical method, combined with statistical tests, to automatically detect key transcript features, including transcriptional start sites (TSSs), transcriptional termination sites (TTSs) and operon organization. Using our method, we obtained 2,764 TSSs and 1,467 TTSs for 1331 and 844 different genes, respectively. Identification of TSSs facilitated further discrimination of 215 putative sigma 38 regulons and 863 potential sigma 70 regulons. Combining the TSSs and TTSs with intergenic distance and co-expression information, we comprehensively annotated the operon organization in S. Typhimurium 14028s. Our results show that directional RNA-seq can be used to detect transcriptional borders at an acceptable resolution of ±10-20 nucleotides. Technical limitations of the RNA-seq procedure may prevent single nucleotide resolution. The automatic transcript border detection methods, statistical models and operon organization pipeline that we have described could be widely applied to RNA-seq studies in other bacteria. Furthermore, the TSSs, TTSs, operons, promoters and unstranslated regions that we have defined for S. Typhimurium 14028s may constitute valuable resources that can be used for

  3. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Farajpour, Zahra [Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rahbarizadeh, Fatemeh, E-mail: rahbarif@modares.ac.ir [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Kazemi, Bahram [Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ahmadvand, Davoud [School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2014-03-28

    Highlights: • A novel nanobody directed to antigenic regions on VEGF was identified. • Our nanobody was successfully purified. • Our nanobody significantly inhibited VEGF-induced proliferation of HUVECs in a dose dependent manner. - Abstract: Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate.

  4. In situ synthesis of nanocomposite membranes: comprehensive improvement strategy for direct methanol fuel cells.

    Science.gov (United States)

    Rao, Siyuan; Xiu, Ruijie; Si, Jiangju; Lu, Shanfu; Yang, Meng; Xiang, Yan

    2014-03-01

    In situ synthesis is a powerful approach to control nanoparticle formation and consequently confers extraordinary properties upon composite membranes relative to conventional doping methods. Herein, uniform nanoparticles of cesium hydrogen salts of phosphotungstic acid (CsPW) are controllably synthesized in situ in Nafion to form CsPW–Nafion nanocomposite membranes with both improved proton conductivity and methanol-crossover suppression. A 101.3% increase of maximum power density has been achieved relative to pristine Nafion in a direct methanol fuel cell (DMFC), indicating a potential pathway for large-scale fabrication of DMFC alternative membranes.

  5. Comparison analysis of superconducting solenoid magnet systems for ECR ion source based on the evolution strategy optimization

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Shao Qing; Lee, Sang Jin [Uiduk University, Gyeongju (Korea, Republic of)

    2015-06-15

    Electron cyclotron resonance (ECR) ion source is an essential component of heavy-ion accelerator. For a given design, the intensities of the highly charged ion beams extracted from the source can be increased by enlarging the physical volume of ECR zone. Several models for ECR ion source were and will be constructed depending on their operating conditions. In this paper three simulation models with 3, 4 and 6 solenoid system were built, but it's not considered anything else except the number of coils. Two groups of optimization analysis are presented, and the evolution strategy (ES) is adopted as an optimization tool which is a technique based on the ideas of mutation, adaptation and annealing. In this research, the volume of ECR zone was calculated approximately, and optimized designs for ECR solenoid magnet system were presented. Firstly it is better to make the volume of ECR zone large to increase the intensity of ion beam under the specific confinement field conditions. At the same time the total volume of superconducting solenoids must be decreased to save material. By considering the volume of ECR zone and the total length of solenoids in each model with different number of coils, the 6 solenoid system represented the highest coil performance. By the way, a certain case, ECR zone volume itself can be essential than the cost. So the maximum ECR zone volume for each solenoid magnet system was calculated respectively with the same size of the plasma chamber and the total magnet space. By comparing the volume of ECR zone, the 6 solenoid system can be also made with the maximum ECR zone volume.

  6. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment.

    Science.gov (United States)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram; Ahmadvand, Davoud

    2014-03-28

    Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. A Hydrazone-Based exo-Directing-Group Strategy for β C-H Oxidation of Aliphatic Amines.

    Science.gov (United States)

    Huang, Zhongxing; Wang, Chengpeng; Dong, Guangbin

    2016-04-18

    Described is a new hydrazone-based exo-directing group (DG) strategy developed for the functionalization of unactivated primary β C-H bonds of aliphatic amines. Conveniently synthesized from protected primary amines, the hydrazone DGs are shown to site-selectively promote the β-acetoxylation and tosyloxylation via five-membered exo-palladacycles. Amines with a wide scope of skeletons and functional groups are tolerated. Moreover, the hydrazone DG can be readily removed, and a one-pot C-H acetoxylation/DG removal protocol was also discovered. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Current strategies and future directions for the prevention of transfusion-transmitted cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Harmon CM

    2017-04-01

    Full Text Available Charles M Harmon, Laura L Cooling Department of Pathology, University of Michigan, Ann Arbor, MI, USA Abstract: Cytomegalovirus (CMV is a pervasive DNA virus that infects a significant portion of individuals worldwide, and may be transmitted through the transfusion of blood products. Although CMV infection is of little consequence in immunocompetent individuals, patients with an impaired immune system are at risk of significant morbidity and mortality. Unlike other blood-borne infectious agents, it is impractical to defer all CMV-positive individuals from blood donation as this would exclude a substantial number of otherwise eligible donors. Other methods such as transfusion of CMV-seronegative and leukoreduced blood products must be employed to prevent the transmission of CMV to at-risk patients. In this study, the widespread use of current strategies for the prevention of transfusion-transmitted CMV (TT-CMV infection and the evidence to support these methods in various at-risk groups were reviewed. In addition, emerging pathogen inactivation technologies that have the potential to eliminate TT-CMV were also discussed. Keywords: blood transfusion, cytomegalovirus, leukoreduction, pathogen inactivation, hematopoietic stem cell transplantation, very low birth weight infants

  9. Direct synthesis of aqueous quantum dots through 4,4'-bipyridine-based twin ligand strategy.

    Science.gov (United States)

    Kalita, Mausam; Cingarapu, Sreeram; Roy, Santanu; Park, Seok Chan; Higgins, Daniel; Jankowiak, Ryszard; Chikan, Viktor; Klabunde, Kenneth J; Bossmann, Stefan H

    2012-04-16

    We report a new class of derivatized 4,4'-bipyridinium ligands for use in synthesizing highly fluorescent, extremely stable, water-soluble CdSe and CdTe quantum dots (QDs) for bioconjugation. We employed an evaporation-condensation technique, also known as solvated metal atom dispersion (SMAD), followed by a digestive ripening procedure. This method has been used to synthesize both metal nanoparticles and semiconductors in the gram scale with several stabilizing ligands in various solvents. The SMAD technique comprised evaporation condensation and stabilization of CdSe or CdTe in tetrahydrofuran. The as-prepared product was then digestively ripened in both water and dimethyl formamide, leading to narrowing of the particle size distributions. The ligands were synthesized by nucleophilic substitution (S(N)2) reactions using 4,4'-bipyridine as a nucleophile. Confocal microscopy images revealed the orange color of the nanocrystalline QDs with diameters of ~5 nm. The size has been confirmed by using transmission electron microscopy. As a part of our strategy, 85% of the 4,4'-bipyridinium salt was synthesized as propionic acid derivative and used to both stabilize the QDs in water and label basic amino acids and different biomarkers utilizing the carboxylic acid functional group. Fifteen percent of the 4,4'-bipyridinium salt was synthesized as N-propyl maleimide and used as a second ligand to label any protein containing the amino acid cysteine by means of a 1,4-Michael addition. © 2012 American Chemical Society

  10. Social Work Students’ Use of Knowledge in Direct Practice – Reasons, Strategies and Effects

    Directory of Open Access Journals (Sweden)

    2007-08-01

    Full Text Available This article describes a study of Swedish social work students’ use of knowledge during their field practice. Data was collected by using short written narratives, where the students reflect on situations from practice, situations they experienced as critical or problematic. The narratives were analysed with a method inspired by the interpretation theory of Paul Ricoeur. The article starts with a discussion adhering to the present trend of evidence-based social work practice. This is followed by a study of 144 narratives from social work students containing critical or problematic events. A quantitative description of the material as well as qualitative model of two type-strategies, that social work students use, is presented. The results show, among other things, that students use several forms of knowledge, where facts/evidence is one of several. The study also shows that there is a strong adaptation to varying critical situations. A conclusion is that it is difficult to a priori define the types and proportions of knowledge to use in social work practice.

  11. Direct-acting antivirals and host-targeting strategies to combat enterovirus infections.

    Science.gov (United States)

    Bauer, Lisa; Lyoo, Heyrhyoung; van der Schaar, Hilde M; Strating, Jeroen Rpm; van Kuppeveld, Frank Jm

    2017-06-01

    Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Direct mailing was a successful recruitment strategy for a lung-cancer screening trial.

    Science.gov (United States)

    Hinshaw, Lisa B; Jackson, Sharon A; Chen, Michael Y

    2007-08-01

    To analyze advertising, recruitment methods, and study participant demographics for the National Lung Screening Trial (NLST) site at Wake Forest University School of Medicine to define efficient ways to recruit participants for general clinical trials. Recruitment method data, demographics, geographic location, and date of enrollment were collected from all 1,112 NLST participants. Marketing data and financial records were analyzed to determine the effectiveness of each recruitment method. The total amount spent on advertising was $144,668, with the cost of enrollment per participant averaging $130. For black participants, the recruitment cost per person was $406, whereas for white and other race participants, the cost was $122 (PTV ads cost $382 per participant. Direct mailing to a targeted group was the most efficient way to recruit participants. Printed advertising methods, that is, newspaper ads and brochures, were quite effective, whereas television ads were expensive. Appropriate minority recruitment needs sufficient attention and resources to ensure census groups are adequately represented.

  13. Assessment of a direct hybridization microarray strategy for comprehensive monitoring of genetically modified organisms (GMOs).

    Science.gov (United States)

    Turkec, Aydin; Lucas, Stuart J; Karacanli, Burçin; Baykut, Aykut; Yuksel, Hakki

    2016-03-01

    Detection of GMO material in crop and food samples is the primary step in GMO monitoring and regulation, with the increasing number of GM events in the world market requiring detection solutions with high multiplexing capacity. In this study, we test the suitability of a high-density oligonucleotide microarray platform for direct, quantitative detection of GMOs found in the Turkish feed market. We tested 1830 different 60nt probes designed to cover the GM cassettes from 12 different GM cultivars (3 soya, 9 maize), as well as plant species-specific and contamination controls, and developed a data analysis method aiming to provide maximum throughput and sensitivity. The system was able specifically to identify each cultivar, and in 10/12 cases was sensitive enough to detect GMO DNA at concentrations of ⩽1%. These GMOs could also be quantified using the microarray, as their fluorescence signals increased linearly with GMO concentration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Educational strategies associated with development of problem-solving, critical thinking, and self-directed learning.

    Science.gov (United States)

    Hendricson, William D; Andrieu, Sandra C; Chadwick, D Gregory; Chmar, Jacqueline E; Cole, James R; George, Mary C; Glickman, Gerald N; Glover, Joel F; Goldberg, Jerold S; Haden, N Karl; Meyerowitz, Cyril; Neumann, Laura; Pyle, Marsha; Tedesco, Lisa A; Valachovic, Richard W; Weaver, Richard G; Winder, Ronald L; Young, Stephen K; Kalkwarf, Kenneth L

    2006-09-01

    This article was developed for the Commission on Change and Innovation in Dental Education (CCI), established by the American Dental Education Association. CCI was created because numerous organizations within organized dentistry and the educational community have initiated studies or proposed modifications to the process of dental education, often working to achieve positive and desirable goals but without coordination or communication. The fundamental mission of CCI is to serve as a focal meeting place where dental educators and administrators, representatives from organized dentistry, the dental licensure community, the Commission on Dental Accreditation, the ADA Council on Dental Education and Licensure, and the Joint Commission on National Dental Examinations can meet and coordinate efforts to improve dental education and the nation's oral health. One of the objectives of the CCI is to provide guidance to dental schools related to curriculum design. In pursuit of that objective, this article summarizes the evidence related to this question: What are educational best practices for helping dental students acquire the capacity to function as an entry-level general dentist or to be a better candidate to begin advanced studies? Three issues are addressed, with special emphasis on the third: 1) What constitutes expertise, and when does an individual become an expert? 2) What are the differences between novice and expert thinking? and 3) What educational best practices can help our students acquire mental capacities associated with expert function, including critical thinking and self-directed learning? The purpose of this review is to provide a benchmark that faculty and academic planners can use to assess the degree to which their curricula include learning experiences associated with development of problem-solving, critical thinking, self-directed learning, and other cognitive skills necessary for dental school graduates to ultimately become expert performers as

  15. Biologist Edwin Grant Conklin and the idea of the religious direction of human evolution in the early 1920s.

    Science.gov (United States)

    Pavuk, Alexander

    2017-01-01

    Edwin Grant Conklin, renowned US embryologist and evolutionary popularizer, publicly advocated a social vision of evolution that intertwined science and modernist Protestant theology in the early 1920s. The moral prestige of professional science in American culture - along with Conklin's own elite scientific status - diverted attention from the frequency with which his work crossed boundaries between natural science, religion and philosophy. Writing for broad audiences, Conklin was one of the most significant of the religious and modernist biological scientists whose rhetoric went well beyond simply claiming that certain kinds of religion were amenable to evolutionary science; he instead incorporated religion itself into evolution's broadest workings. A sampling of Conklin's widely-resonant discourse suggests that there was substantially more to the religion-evolution story in the 1920s US than many creationist-centred narratives of the era imply.

  16. A new direction for water management? Indigenous nation building as a strategy for river health

    Directory of Open Access Journals (Sweden)

    Steve Hemming

    2017-06-01

    Full Text Available Indigenous involvement in Australian water management is conventionally driven by a top-down approach by nonIndigenous government agencies, that asks "how do we engage Indigenous people?" and has culminated in the ineffective "consult" and "service delivery" processes evident in mainstream water management planning. This is a hopeful paper that identifies the critical importance of a "nation-based" approach for effective Indigenous engagement in water planning and policy through the work undertaken by the Ngarrindjeri Regional Authority (NRA in the Murray Futures program. The NRA is an Indigenous government in the "settled-south" of Australia. Over past decades, the NRA has developed a range of political technologies that act as tools for redeveloping Ngarrindjeri Nationhood after colonial disempowerment and dispossession. These tools enable better collaboration with nonIndigenous governments, especially in natural resource management policy and practice. In turn, this has better enabled the NRA to exercise a decision-making and planning authority over the lands and waters in its jurisdiction, therefore, more effectively exercising its ongoing duty of care as Country. This paper presents a case study of the Sugar Shack Complex Management Plan, codeveloped by the NRA and the South Australian Government in 2015, to demonstrate the benefits that accrue when Indigenous nations are resourced as authorities responsible for reframing water management and planning approaches to facilitate the equitable collaboration of Indigenous and nonIndigenous worldviews. As a marker of the success of this strategy, the Ngarrindjeri Yarluwar-Ruwe Program, in partnership with the South Australian government, recently won the Australian Riverprize 2015 for delivering excellence in Australian river management.

  17. Automated identification of retinal vessels using a multiscale directional contrast quantification (MDCQ) strategy

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, Yi; Zhang, Xinyuan; Wang, Ningli, E-mail: wningli@vip.163.com, E-mail: puj@upmc.edu [National Engineering Research Center for Ophthalmic Equipments, Beijing, 100730 (China); Gu, Suicheng; Meng, Xin [Imaging Research Center, Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213 (United States); Zheng, Bin [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Pu, Jiantao, E-mail: wningli@vip.163.com, E-mail: puj@upmc.edu [Imaging Research Center, Departments of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213 (United States)

    2014-09-15

    Purpose: A novel algorithm is presented to automatically identify the retinal vessels depicted in color fundus photographs. Methods: The proposed algorithm quantifies the contrast of each pixel in retinal images at multiple scales and fuses the resulting consequent contrast images in a progressive manner by leveraging their spatial difference and continuity. The multiscale strategy is to deal with the variety of retinal vessels in width, intensity, resolution, and orientation; and the progressive fusion is to combine consequent images and meanwhile avoid a sudden fusion of image noise and/or artifacts in space. To quantitatively assess the performance of the algorithm, we tested it on three publicly available databases, namely, DRIVE, STARE, and HRF. The agreement between the computer results and the manual delineation in these databases were quantified by computing their overlapping in both area and length (centerline). The measures include sensitivity, specificity, and accuracy. Results: For the DRIVE database, the sensitivities in identifying vessels in area and length were around 90% and 70%, respectively, the accuracy in pixel classification was around 99%, and the precisions in terms of both area and length were around 94%. For the STARE database, the sensitivities in identifying vessels were around 90% in area and 70% in length, and the accuracy in pixel classification was around 97%. For the HRF database, the sensitivities in identifying vessels were around 92% in area and 83% in length for the healthy subgroup, around 92% in area and 75% in length for the glaucomatous subgroup, around 91% in area and 73% in length for the diabetic retinopathy subgroup. For all three subgroups, the accuracy was around 98%. Conclusions: The experimental results demonstrate that the developed algorithm is capable of identifying retinal vessels depicted in color fundus photographs in a relatively reliable manner.

  18. A direct biocombinatorial strategy toward next generation, mussel-glue inspired saltwater adhesives.

    Science.gov (United States)

    Wilke, Patrick; Helfricht, Nicolas; Mark, Andreas; Papastavrou, Georg; Faivre, Damien; Börner, Hans G

    2014-09-10

    Biological materials exhibit remarkable, purpose-adapted properties that provide a source of inspiration for designing new materials to meet the requirements of future applications. For instance, marine mussels are able to attach to a broad spectrum of hard surfaces under hostile conditions. Controlling wet-adhesion of synthetic macromolecules by analogue processes promises to strongly impact materials sciences by offering advanced coatings, adhesives, and glues. The de novo design of macromolecules to mimic complex aspects of mussel adhesion still constitutes a challenge. Phage display allows material scientists to design specifically interacting molecules with tailored affinity to material surfaces. Here, we report on the integration of enzymatic processing steps into phage display biopanning to expand the biocombinatorial procedure and enable the direct selection of enzymatically activable peptide adhesion domains. Adsorption isotherms and single molecule force spectroscopy show that those de novo peptides mimic complex aspects of bioadhesion, such as enzymatic activation (by tyrosinase), the switchability from weak to strong binders, and adsorption under hostile saltwater conditions. Furthermore, peptide-poly(ethylene oxide) conjugates are synthesized to generate protective coatings, which possess anti-fouling properties and suppress irreversible interactions with blood-plasma protein cocktails. The extended phage display procedure provides a generic way to non-natural peptide adhesion domains, which not only mimic nature but also improve biological sequence sections extractable from mussel-glue proteins. The de novo peptides manage to combine several tasks in a minimal 12-mer sequence and thus pave the way to overcome major challenges of technical wet glues.

  19. Strategies for Directing the Structure and Function of 3D Collagen Biomaterials across Length Scales

    Science.gov (United States)

    Walters, Brandan D.; Stegemann, Jan P.

    2013-01-01

    Collagen type I is a widely used natural biomaterial that has found utility in a variety of biological and medical applications. Its well characterized structure and role as an extracellular matrix protein make it a highly relevant material for controlling cell function and mimicking tissue properties. Collagen type I is abundant in a number of tissues, and can be isolated as a purified protein. This review focuses on hydrogel biomaterials made by reconstituting collagen type I from a solubilized form, with an emphasis on in vitro studies in which collagen structure can be controlled. The hierarchical structure of collagen from the nanoscale to the macroscale is described, with an emphasis on how structure is related to function across scales. Methods of reconstituting collagen into hydrogel materials are presented, including molding of macroscopic constructs, creation of microscale modules, and electrospinning of nanoscale fibers. The modification of collagen biomaterials to achieve desired structures and functions is also addressed, with particular emphasis on mechanical control of collagen structure, creation of collagen composite materials, and crosslinking of collagenous matrices. Biomaterials scientists have made remarkable progress in rationally designing collagen-based biomaterials and in applying them to both the study of biology and for therapeutic benefit. This broad review illustrates recent examples of techniques used to control collagen structure, and to thereby direct its biological and mechanical functions. PMID:24012608

  20. Direct-injection strategies for a hydrogen-fueled engine : an optical and numerical investigation

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, S.; Salazar, V. [Sandia National Labs, Albuquerque, NM (United States); Scarcelli, R.; Wallner, T. [Argonne National Lab, Argonne, IL (United States)

    2009-07-01

    Vehicles with hydrogen-fueled engines are competitive with systems based on fuel cells. There is a lack of fundamental knowledge about in-cylinder processes in hydrogen direct injection engines. This presentation discussed a study that used a variety of injector configurations to establish a broad database. A light-load conditions that can profit from stratification was investigated. Several results were presented, including the 5-hole nozzle produced an asymmetric jet pattern which may be good for late injection. Very lean regions in the wake of the transient jets were found to be similar to those found in diesel injection. The 13-hole nozzle demonstrated complete jet collapse, consistent with Schlieren imaging by Petersen. Stratification made efficiency sensitive to the targeting of the single-hole injector. Computational fluid dynamics with a commercially available code aimed to improve the process of design optimization. The simulation predicted less fuel dispersion than was experimentally measured. Details of the fuel penetration were captured. It was concluded that for the single-hole nozzle, the pre-spark fuel distribution is consistent with results from the fired engine. tabs., figs.

  1. Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

    Science.gov (United States)

    Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

    2017-07-11

    The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

  2. The effect of EU derogation strategies on the compliance costs of the nitrate directive.

    Science.gov (United States)

    Van der Straeten, Bart; Buysse, Jeroen; Nolte, Stephan; Lauwers, Ludwig; Claeys, Dakerlia; Van Huylenbroeck, Guido

    2012-04-01

    Within the framework of the nitrate directive, member states have the opportunity to apply for derogation, i.e. increasing fertilisation standards under certain conditions. Several EU regions have utilised this opportunity, but each in a different way, resulting in six very different derogation policies within the EU in 2009. This paper focuses on the differences between the policies applied and makes an assessment with regard to the impact of these differences on the application rate for derogation, the manure surplus and the cost of allocating manure. Based on the MP-MAS model described by Van der Straeten et al. (2010) the different scenarios are applied on a single case area (Flanders) and the economic effects have been simulated. Results show considerable differences between the policy alternatives, leading to the conclusion that member states not only have to focus on whether or not to allow derogation, but also on the actual details of the derogation policy. Granting derogation at parcel level (plot of land), instead of farm level, increases the potential effect of derogation; the level of increase in fertilisation standards under derogation determines the application rate for derogation: a higher increase leads to a higher application rate. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Direct flow separation strategy, to isolate no-carrier-added {sup 90}Nb from irradiated Mo or Zr targets

    Energy Technology Data Exchange (ETDEWEB)

    Radchenko, Valery; Roesch, Frank [Mainz Univ. (Germany). Inst. of Nuclear Chemistry; Filosofov, Dmitry V.; Dadakhanov, Jakhongir [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Karaivanov, Dimitar V. [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Bulgarian Academy of Sciences, Sofia (Bulgaria). Inst. for Nuclear Research and Nuclear Energy; Marinova, Atanaska [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Sofia Univ. (Bulgaria). Faculty of Chemistry and Pharmacy; Baimukhanova, Ayagoz [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Institute of Nuclear Physics of the Republic of Kazakhstan, Almaty (Kazakhstan)

    2016-11-01

    {sup 90}Nb has an intermediate half-life of 14.6 h, a high positron branching of 53% and optimal β{sup +} emission energy of only E{sub mean} 0.35 MeV per decay. These favorable characteristics suggest it may be a potential candidate for application in immuno-PET. Our recent aim was to conduct studies on distribution coefficients for Zr{sup IV} and Nb{sup V} in mixtures of HCl/H{sub 2}O{sub 2} and HCl/oxalic acid for anion exchange resin (AG 1 x 8) and UTEVA resin to develop a ''direct flow'' separation strategy for {sup 90}Nb. The direct flow concept refers to a separation accomplished using a single eluent on multiple columns, effectively streamlining the separation process and increasing the time efficiency. Finally, we also demonstrated that this separation strategy is applicable to the production of the positron emitter {sup 90}Nb via the irradiation of molybdenum targets and isolation of {sup 90}Nb from the irradiated molybdenum target.

  4. Embedded and Direct Metacognitive Strategy Instruction and its Effects on the Metacognitive Awareness of Tertiary Level Malaysian ESL Listeners

    Directory of Open Access Journals (Sweden)

    Siew Ean Lye

    2018-01-01

    Full Text Available This small-scale quasi-experimental study compared the effects of metacognitive strategy instruction using two pedagogical approaches on the metacognitive awareness of Malaysian ESL listeners. Embedded and direct strategy instruction was delivered using the Metacognitive Pedagogical Sequence and Cognitive Academic Language Learning Approach instructional models respectively. 45 tertiary level students were randomly selected and assigned to two treatment groups to receive metacognitive instruction over a training period of five weeks. Paired-samples t-test results on participants‟ metacognitive awareness, as measured using the Metacognitive Awareness Listening Questionnaire (MALQ were inclusive despite significant improvements in their IELTS listening scores. No significant development was recorded in the overall MALQ scores but there were significant changes in three out of the five metacognitive awareness factors. Results further layered according to participants‟ listening proficiency levels (low, intermediate and high to examine if differences existed among the listening levels similarly showed no significant difference. These results suggest that ESL listeners‟ metacognitive awareness may not be easily developed with strategy instruction, regardless of the instructional approaches.

  5. Persuasion strategies and sexual solicitations and interactions in online sexual grooming of adolescents: Modeling direct and indirect pathways.

    Science.gov (United States)

    Gámez-Guadix, Manuel; Almendros, Carmen; Calvete, Esther; De Santisteban, Patricia

    2018-02-01

    Online sexual grooming and exploitation of adolescents is receiving increasing social attention. Drawing on a social influence framework, the aim of this study was to test a model of the direct and mediated relationships between an adult's use of persuasion strategies and online sexual grooming of early adolescents. The initial sample of the study consisted of 2731 early Spanish adolescents between 12 and 15 years old (50.6% female). Of these, 196 adolescents (7.17% of the total; 53% girls) were involved in online grooming (mean age = 14.93, SD = 0.90). Persuasion strategies by the adult through internet increased the probability of using deceit, bribery, and the minor's nonsexual involvement. In addition, deceit and bribery were associated with higher rates of sexual solicitation, which in turn increased abusive sexual interactions. Understanding strategies used by adults to groom minors contributes to the prevention of and intervention in this crucial societal problem. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  6. Making decisions based on an imperfect ensemble of climate simulators: strategies and future directions

    Science.gov (United States)

    Sanderson, B. M.

    2017-12-01

    The CMIP ensembles represent the most comprehensive source of information available to decision-makers for climate adaptation, yet it is clear that there are fundamental limitations in our ability to treat the ensemble as an unbiased sample of possible future climate trajectories. There is considerable evidence that models are not independent, and increasing complexity and resolution combined with computational constraints prevent a thorough exploration of parametric uncertainty or internal variability. Although more data than ever is available for calibration, the optimization of each model is influenced by institutional priorities, historical precedent and available resources. The resulting ensemble thus represents a miscellany of climate simulators which defy traditional statistical interpretation. Models are in some cases interdependent, but are sufficiently complex that the degree of interdependency is conditional on the application. Configurations have been updated using available observations to some degree, but not in a consistent or easily identifiable fashion. This means that the ensemble cannot be viewed as a true posterior distribution updated by available data, but nor can observational data alone be used to assess individual model likelihood. We assess recent literature for combining projections from an imperfect ensemble of climate simulators. Beginning with our published methodology for addressing model interdependency and skill in the weighting scheme for the 4th US National Climate Assessment, we consider strategies for incorporating process-based constraints on future response, perturbed parameter experiments and multi-model output into an integrated framework. We focus on a number of guiding questions: Is the traditional framework of confidence in projections inferred from model agreement leading to biased or misleading conclusions? Can the benefits of upweighting skillful models be reconciled with the increased risk of truth lying outside the

  7. Direct approaches to nitriles via highly efficient nitrogenation strategy through C-H or C-C bond cleavage.

    Science.gov (United States)

    Wang, Teng; Jiao, Ning

    2014-04-15

    Because of the importance of nitrogen-containing compounds in chemistry and biology, organic chemists have long focused on the development of novel methodologies for their synthesis. For example, nitrogen-containing compounds show up within functional materials, as top-selling drugs, and as bioactive molecules. To synthesize these compounds in a green and sustainable way, researchers have focused on the direct functionalization of hydrocarbons via C-H or C-C bond cleavage. Although researchers have made significant progress in the direct functionalization of simple hydrocarbons, direct C-N bond formation via C-H or C-C bond cleavage remains challenging, in part because of the unstable character of some N-nucleophiles under oxidative conditions. The nitriles are versatile building blocks and precursors in organic synthesis. Recently, chemists have achieved the direct C-H cyanation with toxic cyanide salts in the presence of stoichiometric metal oxidants. In this Account, we describe recent progress made by our group in nitrile synthesis. C-H or C-C bond cleavage is a key process in our strategy, and azides or DMF serve as the nitrogen source. In these reactions, we successfully realized direct nitrile synthesis using a variety of hydrocarbon groups as nitrile precursors, including methyl, alkenyl, and alkynyl groups. We could carry out C(sp(3))-H functionalization on benzylic, allylic, and propargylic C-H bonds to produce diverse valuable synthetic nitriles. Mild oxidation of C═C double-bonds and C≡C triple-bonds also produced nitriles. The incorporation of nitrogen within the carbon skeleton typically involved the participation of azide reagents. Although some mechanistic details remain unclear, studies of these nitrogenation reactions implicate the involvement of a cation or radical intermediate, and an oxidative rearrangement of azide intermediate produced the nitrile. We also explored environmentally friendly oxidants, such as molecular oxygen, to make our

  8. Calibration strategy for semi-quantitative direct gas analysis using inductively coupled plasma mass spectrometry

    International Nuclear Information System (INIS)

    Gerdes, Kirk; Carter, Kimberly E.

    2011-01-01

    A process is described by which an ICP-MS equipped with an Octopole Reaction System (ORS) is calibrated using liquid phase standards to facilitate direct analysis of gas phase samples. The instrument response to liquid phase standards is analyzed to produce empirical factors relating ion generation and transmission efficiencies to standard operating parameters. Empirical factors generated for liquid phase samples are then used to produce semi-quantitative analysis of both mixed liquid/gas samples and pure gas samples. The method developed is similar to the semi-quantitative analysis algorithms in the commercial software, which have here been expanded to include gas phase elements such as Xe and Kr. Equations for prediction of relative ionization efficiencies and isotopic transmission are developed for several combinations of plasma operating conditions, which allows adjustment of limited parameters between liquid and gas injection modes. In particular, the plasma temperature and electron density are calculated from comparison of experimental results to the predictions of the Saha equation. Comparisons between operating configurations are made to determine the robustness of the analysis to plasma conditions and instrument operating parameters. Using the methods described in this research, the elemental concentrations in a liquid standard containing 45 analytes and treated as an unknown sample were quantified accurately to ± 50% for most elements using 133 Cs as a single internal reference. The method is used to predict liquid phase mercury within 12% of the actual concentration and gas phase mercury within 28% of the actual concentration. The results verify that the calibration method facilitates accurate semi-quantitative, gas phase analysis of metal species with sufficient sensitivity to quantify metal concentrations lower than 1 ppb for many metallic analytes.

  9. ARTIFICIAL SELECTION FOR DEVELOPMENTAL TIME IN DROSOPHILA-MELANOGASTER IN RELATION TO THE EVOLUTION OF AGING - DIRECT AND CORRELATED RESPONSES

    NARCIS (Netherlands)

    ZWAAN, B; BIJLSMA, R; HOEKSTRA, RF

    A wild-type strain of Drosophila melanogaster was successfully selected for both fast and slow larval development. The realized heritabilities (h(2)) ranged from 0.20 to 0.30 for the fast lines and 0.35 to 0.60 for the slow lines. The selection applied is relevant in relation to the evolution of

  10. Assessment of the environmental status in Hellenic coastal waters (Eastern Mediterranean: from the Water Framework Directive to the Marine Strategy Water Framework Directive.

    Directory of Open Access Journals (Sweden)

    N. SIMBOURA

    2014-11-01

    Full Text Available A  methodology is presented to assess the environmental status sensu the Marine Strategy Water Framework Directive (MSFD based on data obtained from the monitoring of water quality in the Hellenic coastal waters within the Water Framework Directive (WFD.   An adapted decision tree used for integrating the results of the WFD in the Basque country was applied. Modifications lie to the evaluation of the physicochemical status based on a eutrophication index developed for Eastern Mediterranean waters. Results on hydromorphological, physicochemical and biological elements are presented. The chemical status was evaluated based on measurements of heavy metals in water. The evaluation of the biological quality was based on the use of metrics developed for phytoplankton biomass, benthic macroinvertebrates and macroalgae updated to accommodate MSFD needs. Results on the integrative status of the water bodies were validated by correlating classification results with a pressure index and environmental indicators in water column and sediment. Following this decision tree the majority of stations expected to be at risk of achieving the good status were found in moderate status. Benthos was found to be the element with the closest agreement with the integrated final status having an increased weighting in the decision tree. The quality of benthos and in some  limited cases  the eutrophication index determined largely the final status. The highest disagreement with the integrative classification was produced by macroalgae. All indicators used correlated with water and sediment parameters but benthos correlated better with sediment factors while phytoplankton and eutrophication index with water column parameters.

  11. Recruitment of young adults for weight gain prevention: randomized comparison of direct mail strategies.

    Science.gov (United States)

    Crane, Melissa M; LaRose, Jessica Gokee; Espeland, Mark A; Wing, Rena R; Tate, Deborah F

    2016-06-08

    Recruiting young adults (ages 18-35 years) into weight gain prevention intervention studies is challenging and men are particularly difficult to reach. This paper describes two studies designed to improve recruitment for a randomized trial of weight gain prevention interventions. Study 1 used a quasi-experimental design to test the effect of two types of direct mailings on their overall reach. Study 2 used a randomized design to test the effect of using targeted messages to increase recruitment of men into the trial. For Study 1, 60,000 male and female young-adult households were randomly assigned to receive either a recruitment brochure or postcard. Visits to recruitment websites during each mailing period were used to assess response to each mailing. Study 2 focused on postcard recruitment only. These households received either a targeted or generic recruitment postcard, where targeted postcards included the word "Men" in the headline text. Response rates to each type of card were categorized based on participant report of mailing received. The reach of the postcards and brochures were similar (421 and 386 website visits, respectively; P = 0.22). Individuals who received the brochure were more likely to initiate the online screener than those who received a postcard (P = 0.01). In Study 2, of those who completed the telephone screening, 60.9 % of men (n = 23) had received the targeted postcard as compared to the generic postcard (39.1 %, P = 0.30). The reverse was true for women (n = 62, 38.7 vs. 61.3 %, P = 0.08). These studies suggest there was little difference in the reach of postcards versus brochures. However, recipients of brochures were more likely to continue to the next stage of study participation. As expected, men's response to the weight gain prevention messages was lower than women's response; but using targeted messages appears to have modestly increased the proportion of male respondents. These studies add to the limited

  12. Optimisation of the Monitoring Strategy of Macroinvertebrate Communities in the River Dender, in Relation to the EU Water Framework Directive

    Directory of Open Access Journals (Sweden)

    Tom P. D’heygere

    2002-01-01

    Full Text Available The Dender basin in Flanders (Belgium was used as a case study to implement the European Union (EU Water Framework Directive. During the last 5 years, ample research on pollution loads and ecological water quality has been done on the Dender River. In addition to biological sampling of macroinvertebrates and fish, automated measurement stations were also used to investigate the spatial-temporal variability of the physical-chemical water quality. This research revealed that the pollution of the Dender River is highly variable. The high nutrient loads result in severe algae blooms during summer, leading to very complex diurnal processes. In this paper, the monitoring strategy for the assessment of the biological water quality in the Dender basin has been reviewed in relation to the EU Water Framework Directive. For this, seasonal macroinvertebrate data were collected and assessed. General trends and hidden structures in these data were analysed by means of classification trees, using different inputs (seasons, river types, and subbasins. Validation of the results was obtained by applying statistical methods. Analysis about the presence and abundance of the macroinvertebrates revealed that there is a distinct difference between the biological water quality in the Dender stem river and its tributaries. There are also seasonal differences between the macroinvertebrate communities when the Dender and its tributaries are examined separately. An optimised monitoring strategy is proposed based on these results and the EU Water Framework Directive. This includes two monitoring campaigns in summer and winter every 3 years. Furthermore, a cyclic monitoring scheme was developed to minimise sampling efforts.

  13. Fundamental Dimensions of Environmental Risk : The Impact of Harsh versus Unpredictable Environments on the Evolution and Development of Life History Strategies.

    Science.gov (United States)

    Ellis, Bruce J; Figueredo, Aurelio José; Brumbach, Barbara H; Schlomer, Gabriel L

    2009-06-01

    The current paper synthesizes theory and data from the field of life history (LH) evolution to advance a new developmental theory of variation in human LH strategies. The theory posits that clusters of correlated LH traits (e.g., timing of puberty, age at sexual debut and first birth, parental investment strategies) lie on a slow-to-fast continuum; that harshness (externally caused levels of morbidity-mortality) and unpredictability (spatial-temporal variation in harshness) are the most fundamental environmental influences on the evolution and development of LH strategies; and that these influences depend on population densities and related levels of intraspecific competition and resource scarcity, on age schedules of mortality, on the sensitivity of morbidity-mortality to the organism's resource-allocation decisions, and on the extent to which environmental fluctuations affect individuals versus populations over short versus long timescales. These interrelated factors operate at evolutionary and developmental levels and should be distinguished because they exert distinctive effects on LH traits and are hierarchically operative in terms of primacy of influence. Although converging lines of evidence support core assumptions of the theory, many questions remain unanswered. This review demonstrates the value of applying a multilevel evolutionary-developmental approach to the analysis of a central feature of human phenotypic variation: LH strategy.

  14. Outward Foreign Direct Investment from BRIC countries: Comparing strategies of Brazilian, Russian, Indian and Chinese multinational companies

    Directory of Open Access Journals (Sweden)

    Wladimir Andreff

    2015-12-01

    Full Text Available An overall comparative study of outward foreign direct investment (OFDI from BRIC countries and strategies conducted by multinational companies (MNCs based in the BRICs is elaborated on with a same methodology for Brazil, Russia, India and China. The comparison pertains to the historical emergence of firms’ internationalisation, their booming expansion in the 2000s then their muddling through the current crisis, the specificities of OFDI from each home country, OFDI geographical distribution and industrial structure, econometric testing of the respective determinants of Brazilian, Russian, Indian and Chinese OFDI, and the role of home countries’ governments vis-à-vis home-based MNCs. Beyond some common characteristics, BRICs’ MNCs exhibit a number of major country-specific features.

  15. An effect-directed strategy for characterizing emerging chemicals in food contact materials made from paper and board

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Bengtström, Linda; Taxvig, Camilla

    2017-01-01

    Food contact materials (FCM) are any type of item intended to come into contact with foods and thus represent a potential source for human exposure to chemicals. Regarding FCMs made of paper and board, information pertaining to their chemical constituents and the potential impacts on human health...... FCMs exhibited activities in at least one assay. As proof-of-principle, FCM samples obtained from a sandwich wrapper and a pizza box were carried through a complete step-by-step multi-tiered approach. The pizza box exhibited ER activity, likely caused by the presence of bisphenol A, dibutyl phthalate......, and benzylbutyl phthalate. The sandwich wrapper exhibited AR antagonism, likely caused by abietic acid and dehydroabietic acid. Migration studies confirmed that the active chemicals can transfer from FCMs to food simulants. In conclusion, we report an effect-directed strategy that can identify hazards posed...

  16. Suppress to Forget: The Effect of a Mindfulness-Based Strategy during an Emotional Item-Directed Forgetting Paradigm

    Science.gov (United States)

    Gamboa, Olga L.; Garcia-Campayo, Javier; Müller, Teresa; von Wegner, Frederic

    2017-01-01

    Forgetting is a common phenomenon in everyday life. Although it often has negative connotations, forgetting is an important adaptive mechanism to avoid loading the memory storage with irrelevant information. A very important aspect of forgetting is its interaction with emotion. Affective events are often granted special and priority treatment over neutral ones with regards to memory storage. As a consequence, emotional information is more resistant to extinction than neutral information. It has been suggested that intentional forgetting serves as a mechanism to cope with unwanted or disruptive emotional memories and the main goal of this study was to assess forgetting of emotional auditory material using the item-method directed forgetting (DF) paradigm using a forgetting strategy based on mindfulness as a means to enhance DF. Contrary to our prediction, the mindfulness-based strategy not only did not improve DF but reduced it for neutral material. These results suggest that an interaction between processes such as response inhibition and attention is required for intentional forgetting to succeed. PMID:28382015

  17. Direct reciprocity in structured populations.

    Science.gov (United States)

    van Veelen, Matthijs; García, Julián; Rand, David G; Nowak, Martin A

    2012-06-19

    Reciprocity and repeated games have been at the center of attention when studying the evolution of human cooperation. Direct reciprocity is considered to be a powerful mechanism for the evolution of cooperation, and it is generally assumed that it can lead to high levels of cooperation. Here we explore an open-ended, infinite strategy space, where every strategy that can be encoded by a finite state automaton is a possible mutant. Surprisingly, we find that direct reciprocity alone does not lead to high levels of cooperation. Instead we observe perpetual oscillations between cooperation and defection, with defection being substantially more frequent than cooperation. The reason for this is that "indirect invasions" remove equilibrium strategies: every strategy has neutral mutants, which in turn can be invaded by other strategies. However, reciprocity is not the only way to promote cooperation. Another mechanism for the evolution of cooperation, which has received as much attention, is assortment because of population structure. Here we develop a theory that allows us to study the synergistic interaction between direct reciprocity and assortment. This framework is particularly well suited for understanding human interactions, which are typically repeated and occur in relatively fluid but not unstructured populations. We show that if repeated games are combined with only a small amount of assortment, then natural selection favors the behavior typically observed among humans: high levels of cooperation implemented using conditional strategies.

  18. Microstructural evolution of direct chill cast Al-15.5Si-4Cu-1Mg-1Ni-0.5Cr alloy during solution treatment

    OpenAIRE

    He Kezhun; Yu Fuxiao; Zhao Dazhi

    2011-01-01

    Heat treatment has important influence on the microstructure and mechanical properties of Al-Si alloys. The most common used heat treatment method for these alloys is solution treatment followed by age-hardening. This paper investigates the microstructural evolution of a direct chill (DC) cast Al-15.5Si-4Cu-1Mg-1Ni-0.5Cr alloy after solution treated at 500, 510, 520 and 530℃, respectively for different times. The major phases observed in the as-cast alloy are α-aluminum dendrite, primary Si p...

  19. Two-dimensional porous architecture of protonated GCN and reduced graphene oxide via electrostatic self-assembly strategy for high photocatalytic hydrogen evolution under visible light

    Energy Technology Data Exchange (ETDEWEB)

    Pu, Chenchen; Wan, Jun; Liu, Enzhou; Yin, Yunchao; Li, Juan; Ma, Yongning [School of Chemical Engineering, Northwest University, Xi’an 710069 (China); Fan, Jun, E-mail: fanjun@nwu.edu.cn [School of Chemical Engineering, Northwest University, Xi’an 710069 (China); Hu, Xiaoyun, E-mail: hxy3275@nwu.edu.cn [School of Physics, Northwest University, Xi’an 710069 (China)

    2017-03-31

    Highlights: • The protonated GCN (pGCN) is prepared by acidic cutting and hydrothermal process. • The pGCN coupled with rGO are synthesized via electrostatic self-assembly strategy. • The pGCN-5 wt% rGO is obtained with a high specific surface area of 115.64 m{sup 2}g{sup −1}. • The pGCN-5 wt% rGO photocatalysts exhibit superb photocatalytic reduction capacity. - Abstract: Herein, porous protonated graphitic carbon nitride (pGCN) is prepared from bulk g-C{sub 3}N{sub 4} (GCN) directly by acidic cutting and hydrothermal process. The holey structure not only provides a lot of bounds on the accelerated and photo induced charge transfer and thus reduce the aggregation, but also endows the GCN with more exposure to the active site. The pGCN is obtained with an increased band gap of 2.91 eV together with a higher specific surface area of 82.76 m{sup 2}g{sup −1}. Meanwhile, the positively charged GCN resulted from the protonation pretreatment is beneficial for improving the interaction with negatively charged GO sheets. Compared with GCN, pGCN-rGO displays a significant decrease of PL intensities and an apparently enhancement of visible-light absorption, resulting a lower charge recombination rate and a better light absorption. Besides, the enhanced charge separation is demonstrated by photoluminescence emission spectroscopy and the transient photocurrent measurement. The photocatalytic performance studies for the degradation of MB indicate that pGCN-rGO exhibits the highest adsorption ability towards dye molecules. In addition, the pGCN-5 wt% rGO composite shows the optimal photocatalytic activity, the photodegradation rate of MB is 99.4% after 80 min of irradiation and the H{sub 2} evolution performance up to 557 μmol g{sup −1}h{sup −1} under visible light, which is much higher than the other control samples.

  20. Budget impact analysis of rivaroxaban vs. warfarin anticoagulation strategy for direct current cardioversion in non-valvular atrial fibrillation patients: the MonaldiVert Economic Study.

    Science.gov (United States)

    Russo, Vincenzo; Rago, Anna; Papa, Andrea A; Bianchi, Valter; Tavoletta, Vincenzo; DE Vivo, Stefano; Cavallaro, Ciro; Nigro, Gerardo; D'Onofrio, Antonio

    2018-02-01

    Rivaroxaban is the first novel oral anticoagulant to receive regulatory approval for non-valvular atrial fibrillation (NVAF) patients who require cardioversion. The MonaldiVert real life experience showed positive benefit-risk profile of short term rivaroxaban administration for transesophageal echocardiogram guided cardioversion in patients who had not achieved adequate pre-procedural vitamin K antagonist (VKA) anticoagulation. Aim of our study was to perform a budget impact analysis of MonaldiVert anticoagulation strategy for direct current cardioversion in NVAF patients and to compare the following costs borne by the Regional Healthcare System (RHS) with those for a hypothetical cohort of identical patients underwent from the beginning to early rivaroxaban treatment before direct current cardioversion. The mean costs per each NVAF patient treated with VKA strategy and rivaroxaban rescue strategy were € 134.53 and € 189.83, respectively. Considering a hypothetical scenario in which all study population would be treated from the beginning with rivaroxaban (rivaroxaban early strategy), the mean cost per patient would have been € 81.11. The total cost borne by the RHS, including the cost of the cardioversion procedure, for the two therapeutic strategies carried out at Monaldi Hospital (VKA strategy and Rivaroxaban rescue strategy) was € 88,458.53. The total cost would be borne by the RHS for rivaroxaban early strategy, if applied to all study population, would have been € 69,989.15 with a saving of € 18,469.38 compared to the actually applied strategy. Rivaroxaban rescue strategy for transesophageal echocardiography guided direct current cardioversion in NVAF patients, who had not achieved adequate pre-procedural VKA anticoagulation, is an effective and safe strategy, which allows to not delay the procedure, reducing times and wastage of cardioversion slots, without substantial costs increase.

  1. Evolution of floral display in Eichhornia paniculata (Pontederiaceae): direct and correlated responses to selection on flower size and number.

    Science.gov (United States)

    Worley, A C; Barrett, S C

    2000-10-01

    Trade-offs between flower size and number seem likely to influence the evolution of floral display and are an important assumption of several theoretical models. We assessed floral trade-offs by imposing two generations of selection on flower size and number in a greenhouse population of bee-pollinated Eichhornia paniculata. We established a control line and two replicate selection lines of 100 plants each for large flowers (S+), small flowers (S-), and many flowers per inflorescence (N+). We compared realized heritabilities and genetic correlations with estimates based on restricted-maximum-likelihood (REML) analysis of pedigrees. Responses to selection confirmed REML heritability estimates (flower size, h2 = 0.48; daily flower number, h2 = 0.10; total flower number, h2 = 0.23). Differences in nectar, pollen, and ovule production between S+ and S- lines supported an overall divergence in investment per flower. Both realized and REML estimates of the genetic correlation between daily and total flower number were r = 1.0. However, correlated responses to selection were inconsistent in their support of a trade-off. In both S- lines, correlated increases in flower number indicated a genetic correlation of r = -0.6 between flower size and number. In contrast, correlated responses in N+ and S+ lines were not significant, although flower size decreased in one N+ line. In addition, REML estimates of genetic correlations between flower size and number were positive, and did not differ from zero when variation in leaf area and age at first flowering were taken into account. These results likely reflect the combined effects of variation in genes controlling the resources available for flowering and genes with opposing effects on flower size and number. Our results suggest that the short-term evolution of floral display is not necessarily constrained by trade-offs between flower size and number, as is often assumed.

  2. Biodegradation of 1,2,3-trichloropropane through directed evolution and heterologous expression of a haloalkane dehalogenase gene

    OpenAIRE

    Bosma, Tjibbe; Damborský, Jiří; Stucki, Gerhard; Janssen, Dick B.

    2002-01-01

    Using a combined strategy of random mutagenesis of haloalkane dehalogenase and genetic engineering of a chloropropanol-utilizing bacterium, we constructed an organism that is capable of growth on 1,2,3-trichloropropane (TCP). This highly toxic and recalcitrant compound is a waste product generated from the manufacture of the industrial chemical epichlorohydrin. Attempts to select and enrich bacterial cultures that can degrade TCP from environmental samples have repeatedly been unsuccessful, p...

  3. Trend of tuberculosis cases under directly observed treatment, short-course strategy in Tabriz, Iran, from 2001 to 2011

    Directory of Open Access Journals (Sweden)

    Zhila Khamnian

    2016-02-01

    Full Text Available Introduction: The universal target under the Millennium Development Goals (MDGs is to reduce the worldwide burden of tuberculosis (TB 2015, and we wanted to evaluate development in TB control by assessment of the time trend in incidence and death rate in Tabriz, Iran. Methods: This was a retrospective trend analysis of the data have been recorded in East Azerbaijan State TB center during 10 years. Data were related to patients have been registered for treatment under the directly observed treatment, short-course (DOTS strategy from 2001 to 2011. Results: In total, 3283 TB patients were treated under DOTS strategy during 2001-2011. Males constituted 55.0% of subjects. The risk was the highest among the productive age group (15-44 years. About 61.0% of cases had pulmonary, and 78.0% of pulmonary TB patients were found to be the sputum smear positive than 46.0% of them were new sputum smear positive, and 2.0% of them were relapse. On average, for sputum smear positive, TB cases from 2005 to 2011; the treatment success rate was 87.3%; the cure rate was 80.2%; the treatment failure rate was 0.5% and death rate was 10.3%. In general, the TB incidence rate for all TB cases was decreased from 11.9-8.1 a 100000 population and the smear-positive pulmonary TB incidence rate were decreased from 4.7 to 4.1 a 100000 population in eastern Azerbaijan province during 2001-2011. Conclusion: In general, we had a decrease in the incidence rate for all of TB cases. In addition, we had a fall in cure rate and had an increase in drug side effects rate in this year that can be because of elevated old people ratio and high death rate by other indirect causes and lack of regular visits and medications taking according to the treatment protocol.

  4. Beating Bias in the Directed Evolution of Proteins: Combining High-Fidelity on-Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction.

    Science.gov (United States)

    Li, Aitao; Acevedo-Rocha, Carlos G; Sun, Zhoutong; Cox, Tony; Xu, Jia Lucy; Reetz, Manfred T

    2018-02-02

    Saturation mutagenesis (SM) constitutes a widely used technique in the directed evolution of selective enzymes as catalysts in organic chemistry and in the manipulation of metabolic paths and genomes, but the quality of the libraries is far from optimal due to the inherent amino acid bias. Herein, it is shown how this fundamental problem can be solved by applying high-fidelity solid-phase chemical gene synthesis on silicon chips followed by efficient gene assembly. Limonene epoxide hydrolase was chosen as the catalyst in the model desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)- and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM library, produced by simultaneous randomization at several residues by using a reduced amino acid alphabet, and the respective synthetic library were constructed and compared. Statistical analysis at the DNA level with massive sequencing demonstrates that, in the synthetic approach, 97 % of the theoretically possible DNA mutants are formed, whereas the traditional SM library contained only about 50 %. Screening at the protein level also showed the superiority of the synthetic library; many highly (R,R)- and (S,S)-selective variants being discovered are not found in the traditional SM library. With the prices of synthetic genes decreasing, this approach may point the way to future directed evolution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Structures of the Apo and FAD-bound forms of 2-hydroxybiphenyl 3-monooxygenase (HbpA) locate activity hotspots identified by using directed evolution.

    Science.gov (United States)

    Jensen, Chantel N; Mielke, Tamara; Farrugia, Joseph E; Frank, Annika; Man, Henry; Hart, Sam; Turkenburg, Johan P; Grogan, Gideon

    2015-04-13

    The FAD-dependent monooxygenase HbpA from Pseudomonas azelaica HBP1 catalyses the hydroxylation of 2-hydroxybiphenyl (2HBP) to 2,3-dihydroxybiphenyl (23DHBP). HbpA has been used extensively as a model for studying flavoprotein hydroxylases under process conditions, and has also been subjected to directed-evolution experiments that altered its catalytic properties. The structure of HbpA has been determined in its apo and FAD-complex forms to resolutions of 2.76 and 2.03 Å, respectively. Comparisons of the HbpA structure with those of homologues, in conjunction with a model of the reaction product in the active site, reveal His48 as the most likely acid/base residue to be involved in the hydroxylation mechanism. Mutation of His48 to Ala resulted in an inactive enzyme. The structures of HbpA also provide evidence that mutants achieved by directed evolution that altered activity are comparatively remote from the substrate-binding site. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Direct laser metal deposition of WC/Co/Cr powder by means of the functionally graded materials strategy

    Science.gov (United States)

    Angelastro, A.; Campanelli, S. L.

    2017-12-01

    One of the many applications of direct laser metal deposition (DLMD) is the realization of multilayer thick coatings having particular mechanical characteristics, such as high hardness. The objective of this work was to obtain a thick, very hard and wear resistant coating, containing a high percentage of tungsten carbide (WC), on an AISI 304 stainless steel substrate. In order to achieve this result, a tungsten carbide-cobalt-chrome (WC/Co/Cr) powder was processed by the DLMD method. WC/Co/Cr is a composite widely used as a wear-resistant material for cutting tools, molds, coatings and other severe applications. Because of its high hardness, poor ductility and low thermal expansion coefficient, depositing this material directly on the stainless steel substrate is very difficult. In order to overcome this problem, the strategy of functionally graded materials (FGM) was used. Colmonoy 227-F nickel alloy was chosen for this purpose in order to generate a mixture with the WC/Co/Cr powder. Four different materials were deposited, layer by layer, by mixing Colmonoy 227-F with an increasing amount of WC/Co/Cr powders, until obtaining a thick surface coating with a maximum amount of WC of 77.4 wt%. For each powder mixture, a mathematical model was applied to calculate optimal values of translation speed and overlap percentages. A metallographic examination was performed in order to detect macro- and micro-structures of the different materials. Finally, Vickers micro-hardness was measured at various locations along the transverse section to appreciate the gradual increase of the FGM hardness, starting from the substrate and culminating at the top surface of the last deposited material.

  7. Evolution of Various Library Instruction Strategies: Using Student Feedback to Create and Enhance Online Active Learning Assignments

    Directory of Open Access Journals (Sweden)

    Marcie Lynne Jacklin

    2013-06-01

    Full Text Available This case study traces the evolution of library assignments for biological science students from paper-based workbooks in a blended (hands-on workshop to blended learning workshops using online assignments to online active learning modules which are stand-alone without any face-to-face instruction. As the assignments evolved to adapt to online learning supporting materials in the form of PDFs (portable document format, screen captures and screencasting were embedded into the questions as teaching moments to replace face-to-face instruction. Many aspects of the evolution of the assignment were based on student feedback from evaluations, input from senior lab demonstrators and teaching assistants, and statistical analysis of the students’ performance on the assignment. Advantages and disadvantages of paper-based and online assignments are discussed. An important factor for successful online learning may be the ability to get assistance.

  8. Evolution of a Directional Wave Spectrum in a 3D Marginal Ice Zone with Random Floe Size Distribution

    Science.gov (United States)

    Montiel, F.; Squire, V. A.

    2013-12-01

    A new ocean wave/sea-ice interaction model is proposed that simulates how a directional wave spectrum evolves as it travels through a realistic marginal ice zone (MIZ), where wave/ice dynamics are entirely governed by coherent conservative wave scattering effects. Field experiments conducted by Wadhams et al. (1986) in the Greenland Sea generated important data on wave attenuation in the MIZ and, particularly, on whether the wave spectrum spreads directionally or collimates with distance from the ice edge. The data suggest that angular isotropy, arising from multiple scattering by ice floes, occurs close to the edge and thenceforth dominates wave propagation throughout the MIZ. Although several attempts have been made to replicate this finding theoretically, including by the use of numerical models, none have confronted this problem in a 3D MIZ with fully randomised floe distribution properties. We construct such a model by subdividing the discontinuous ice cover into adjacent infinite slabs of finite width parallel to the ice edge. Each slab contains an arbitrary (but finite) number of circular ice floes with randomly distributed properties. Ice floes are modeled as thin elastic plates with uniform thickness and finite draught. We consider a directional wave spectrum with harmonic time dependence incident on the MIZ from the open ocean, defined as a continuous superposition of plane waves traveling at different angles. The scattering problem within each slab is then solved using Graf's interaction theory for an arbitrary incident directional plane wave spectrum. Using an appropriate integral representation of the Hankel function of the first kind (see Cincotti et al., 1993), we map the outgoing circular wave field from each floe on the slab boundaries into a directional spectrum of plane waves, which characterizes the slab reflected and transmitted fields. Discretizing the angular spectrum, we can obtain a scattering matrix for each slab. Standard recursive

  9. Genetic algorithm-based optimization of testing and maintenance under uncertain unavailability and cost estimation: A survey of strategies for harmonizing evolution and accuracy

    International Nuclear Information System (INIS)

    Villanueva, J.F.; Sanchez, A.I.; Carlos, S.; Martorell, S.

    2008-01-01

    This paper presents the results of a survey to show the applicability of an approach based on a combination of distribution-free tolerance interval and genetic algorithms for testing and maintenance optimization of safety-related systems based on unavailability and cost estimation acting as uncertain decision criteria. Several strategies have been checked using a combination of Monte Carlo (simulation)--genetic algorithm (search-evolution). Tolerance intervals for the unavailability and cost estimation are obtained to be used by the genetic algorithms. Both single- and multiple-objective genetic algorithms are used. In general, it is shown that the approach is a robust, fast and powerful tool that performs very favorably in the face of noise in the output (i.e. uncertainty) and it is able to find the optimum over a complicated, high-dimensional nonlinear space in a tiny fraction of the time required for enumeration of the decision space. This approach reduces the computational effort by means of providing appropriate balance between accuracy of simulation and evolution; however, negative effects are also shown when a not well-balanced accuracy-evolution couple is used, which can be avoided or mitigated with the use of a single-objective genetic algorithm or the use of a multiple-objective genetic algorithm with additional statistical information

  10. A Joint Optimal Decision on Shipment Size and Carbon Reduction under Direct Shipment and Peddling Distribution Strategies

    Directory of Open Access Journals (Sweden)

    Daiki Min

    2017-11-01

    Full Text Available Recently, much research has focused on lowering carbon emissions in logistics. This paper attempts to contribute to the literature on the joint shipment size and carbon reduction decisions by developing novel models for distribution systems under direct shipment and peddling distribution strategies. Unlike the literature that has simply investigated the effects of carbon costs on operational decisions, we address how to reduce carbon emissions and logistics costs by adjusting shipment size and making an optimal decision on carbon reduction investment. An optimal decision is made by analyzing the distribution cost including not only logistics and carbon trading costs but also the cost for adjusting carbon emission factors. No research has explicitly considered the two sources of carbon emissions, but we develop a model covering the difference in managing carbon emissions from transportation and storage. Structural analysis guides how to determine an optimal shipment size and emission factors in a closed form. Moreover, we analytically prove the possibility of reducing the distribution cost and carbon emissions at the same time. Numerical analysis follows validation of the results and demonstrates some interesting findings on carbon and distribution cost reduction.

  11. A multi-mode operation control strategy for flexible microgrid based on sliding-mode direct voltage and hierarchical controls.

    Science.gov (United States)

    Zhang, Qinjin; Liu, Yancheng; Zhao, Youtao; Wang, Ning

    2016-03-01

    Multi-mode operation and transient stability are two problems that significantly affect flexible microgrid (MG). This paper proposes a multi-mode operation control strategy for flexible MG based on a three-layer hierarchical structure. The proposed structure is composed of autonomous, cooperative, and scheduling controllers. Autonomous controller is utilized to control the performance of the single micro-source inverter. An adaptive sliding-mode direct voltage loop and an improved droop power loop based on virtual negative impedance are presented respectively to enhance the system disturbance-rejection performance and the power sharing accuracy. Cooperative controller, which is composed of secondary voltage/frequency control and phase synchronization control, is designed to eliminate the voltage/frequency deviations produced by the autonomous controller and prepare for grid connection. Scheduling controller manages the power flow between the MG and the grid. The MG with the improved hierarchical control scheme can achieve seamless transitions from islanded to grid-connected mode and have a good transient performance. In addition the presented work can also optimize the power quality issues and improve the load power sharing accuracy between parallel VSIs. Finally, the transient performance and effectiveness of the proposed control scheme are evaluated by theoretical analysis and simulation results. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Using Direct Policy Search to Identify Robust Strategies in Adapting to Uncertain Sea Level Rise and Storm Surge

    Science.gov (United States)

    Garner, G. G.; Keller, K.

    2017-12-01

    Sea-level rise poses considerable risks to coastal communities, ecosystems, and infrastructure. Decision makers are faced with deeply uncertain sea-level projections when designing a strategy for coastal adaptation. The traditional methods have provided tremendous insight into this decision problem, but are often silent on tradeoffs as well as the effects of tail-area events and of potential future learning. Here we reformulate a simple sea-level rise adaptation model to address these concerns. We show that Direct Policy Search yields improved solution quality, with respect to Pareto-dominance in the objectives, over the traditional approach under uncertain sea-level rise projections and storm surge. Additionally, the new formulation produces high quality solutions with less computational demands than the traditional approach. Our results illustrate the utility of multi-objective adaptive formulations for the example of coastal adaptation, the value of information provided by observations, and point to wider-ranging application in climate change adaptation decision problems.

  13. SOFC direct fuelling with high-methane gases: Optimal strategies for fuel dilution and upgrade to avoid quick degradation

    International Nuclear Information System (INIS)

    Baldinelli, A.; Barelli, L.; Bidini, G.; Di Michele, A.; Vivani, R.

    2016-01-01

    Highlights: • SOFCs are operated on natural gas and biogas direct feeding. • Methane partial oxidation and dry reforming are compared. • The optimal oxygen-to-carbon stoichiometry to avoid degradation is determined for both natural gas and biogas. • NiYSZ anodes degradation mechanisms are investigated though SEM-EDX and XRD. - Abstract: In the outlook of the transition to the carbon-free society, low-carbon gases, such as natural gas or biogas, are very promising. The first is commonly used for stationary applications based on Solid Oxide Fuel Cells (SOFCs) equipped with external reformers. Similar installations are required when the SOFC is run on biogas. Yet, high SOFC operative temperature enables internal decomposition of light hydrocarbons, therefore allowing the suppression of external reforming. Evidently, this brings about benefits in terms of system complexity and cost reduction. Nonetheless, unlike reformate fuels, direct exposure to large amount of methane favours SOFC anodes degradation. Implementing a systematic experimental approach, this paper aims at determining a simple operative strategy to carry out direct feeding without meeting with quick degradation issues, producing interesting outcomes with regards to the management of SOFC-based systems. Particularly, the regulation of the oxygen-to-carbon (O/C) relative fraction of the fuel through air addition to natural gas and partial CO_2 separation from biogas is helpful in the prevention of those mechanisms. In this study, NiYSZ anode SOFCs are exposed to air-diluted natural gas and upgraded biogas, featuring O/C between 0.2 and 1.2. Tracing these cases, at 800 °C and 500 mA/cm"2 constant load, cell performances are measured over a time interval of 100 h. Finally, post-mortem analysis is performed on the specimens to investigate material morphological changes after the exposure to high-methane fuels. Results showed that O/C = 0.8 (+63% air) is the best case to employ air-diluted natural gas

  14. Segregation and microstructure evolution in chill cast and directionally solidified Ni-Mn-Sn metamagnetic shape memory alloys

    Science.gov (United States)

    Czaja, P.; Wierzbicka-Miernik, A.; Rogal, Ł.

    2018-06-01

    A multiphase solidification behaviour is confirmed for a range of Ni-rich and Ni-deficient Ni-Mn-Sn induction cast and directionally solidified (Bridgman) alloys. The composition variation is primarily linked to the changing Mn/Sn ratio, whereas the content of Ni remains largely stable. The partitioning coefficients for the Ni50Mn37Sn13 and Ni46Mn41.5Sn12.5 Bridgman alloys were obtained according to the Scheil equation based on the composition distribution along the longitudinal cross section of the ingots. Homogenization heat treatment performed for 72 h at 1220 K turned out sufficient for ensuring chemical uniformity on the macro- and microscale. It is owed to a limited segregation length scale due to slow cooling rates adopted for the directional solidification process.

  15. Cost-effectiveness analysis of two treatment strategies for chronic hepatitis C before and after access to direct-acting antivirals in Spain.

    Science.gov (United States)

    Turnes, Juan; Domínguez-Hernández, Raquel; Casado, Miguel Ángel

    To evaluate the cost-effectiveness of a strategy based on direct-acting antivirals (DAAs) following the marketing of simeprevir and sofosbuvir (post-DAA) versus a pre-direct-acting antiviral strategy (pre-DAA) in patients with chronic hepatitis C, from the perspective of the Spanish National Health System. A decision tree combined with a Markov model was used to estimate the direct health costs (€, 2016) and health outcomes (quality-adjusted life years, QALYs) throughout the patient's life, with an annual discount rate of 3%. The sustained virological response, percentage of patients treated or not treated in each strategy, clinical characteristics of the patients, annual likelihood of transition, costs of treating and managing the disease, and utilities were obtained from the literature. The cost-effectiveness analysis was expressed as an incremental cost-effectiveness ratio (incremental cost per QALY gained). A deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. The post-DAA strategy showed higher health costs per patient (€30,944 vs. €23,707) than the pre-DAA strategy. However, it was associated with an increase of QALYs gained (15.79 vs. 12.83), showing an incremental cost-effectiveness ratio of €2,439 per QALY. The deterministic sensitivity analysis and the probabilistic sensitivity analysis showed the robustness of the results, with the post-DAA strategy being cost-effective in 99% of cases compared to the pre-DAA strategy. Compared to the pre-DAA strategy, the post-DAA strategy is efficient for the treatment of chronic hepatitis C in Spain, resulting in a much lower cost per QALY than the efficiency threshold used in Spain (€30,000 per QALY). Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  16. Radiological and acetomorphine analysis of the symmetry and direction of evolution of skulls from some historic populations

    International Nuclear Information System (INIS)

    Gawlikowska-Sroka, A.

    2006-01-01

    Introduction: Asymmetry is a common phenomenon in nature. It is typical for the human body and for the skull as its part. Knowledge of asymmetry and normal anatomy, especially of variability which does not represent pathology but distinguishes individuals is the basis for correct interpretation of radiological findings concerning the skull both in research and diagnostic examinations widely performed in surgery, neurology, neurosurgery, internal medicine, or pediatrics. Analysis of fluctuating asymmetry reveals the influence of stress factors on human development and the ability of the organism to defend itself against stress.The aim of this work was to analyse the asymmetry of skulls from some historic populations and to describe changes in their anatomy over the ages. Material and methods: The material consisted of three skull groups: one contemporary with 82 skulls and two mediaeval (52 skulls from Cedynia and 77 skulls from Grodek on Bug). Direct measurements were done and the skull was X-rayed in the Posterior-Anterior and skull-base projections. Images were scanned and calibrated with MicroStation 95 Academic Edition software. Helmert's transformation with first-order polynomial was done to attain a suitable geometry. Vectorisation of axes and areas was performed on reference material. Using tools for measurement of vector elements, the distance between bilateral points of both sides of the skull were obtained. Data were analysed statistically. Results: The results of measurements were used to study the directional and fluctuating asymmetry. It was found that asymmetry of the skull was present in both historic populations. The following conclusions were drawn: changes in the distribution of directional and fluctuating asymmetry for individual dimensions have taken place over the ages. A high level of directional asymmetry in the facial part and fluctuating asymmetry in the calvaria is typical for contemporary skulls. The reverse is true for relations in the

  17. Car firms and low-emission vehicles: The evolution of incumbents’ strategies in relation to policy developments

    NARCIS (Netherlands)

    Bohnsack, R.

    2013-01-01

    This dissertation explores the developments in the international car industry from 1997 to 2010 in relation to low-emission vehicles, with specific attention to electric vehicles. More specifically, the study seeks to better understand strategies of car manufacturers and the interplay of

  18. The Cook, the Thief, his Wife and her Lovert : on the evolution of the human reproductive strategy

    NARCIS (Netherlands)

    Schuiling, GA

    2003-01-01

    Human reproductive strategy differs from that of most other mammals, including Apes such as the closely related chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). For example, humans, although basically polygamic, exhibit a strong tendency to (serial) monogamy and-very rare for a

  19. A Concept-Mapping Strategy for Assessing Conceptual Change in a Student-Directed, Research-Based Geoscience Course

    Science.gov (United States)

    Rebich, S.

    2003-12-01

    topic of global climate change, for which students were provided with a list of questions to guide their thoughts during the concept map construction. Following the pre-test, students were not exposed to further concept mapping until the end of the course, when they were asked to complete a "post-test" consisting of exactly the same task. In addition to a summary of our results, this paper presents an overview of available digital concept-mapping tools, proposed scoring techniques, and design principles to keep in mind when designing a concept-mapping assessment program. We also discuss our experience with concept map assessment, the insights it provided into the evolution in student understanding of global climate change that resulted from the course, and our ideas about the potential role of concept mapping in an overall assessment program for interdisciplinary and/or student-directed curricula.

  20. A prospective study of ocular toxicity in patients receiving ethambutol as a part of directly observed treatment strategy therapy

    Directory of Open Access Journals (Sweden)

    Pragati Garg

    2015-01-01

    Full Text Available Background and Objectives: India is among the largest countries to implement the revised National Tuberculosis Control Program (RNTCP. This program provides intermittent regimens to the patients, where the doses of isoniazid and ethambutol are more as compared to the daily regimen, which is a cause of concern, particularly with regard to the ocular toxicity of ethambutol. The present study was undertaken to explore the ocular toxicity in the patients registered under the program. Materials and Methods: This was a prospective single center cohort study of 64 patients of categories I and II, coming to the RNTCP-Directly Observed Treatment Strategy (DOTS center at a tertiary care referral hospital. The detailed history, best corrected visual acuity, fundus examination, and color vision test were carried out in all patients at the start of treatment and then at the first and second month of treatment. Results: Loss in visual acuity from the baseline was noted at the second month follow up in 12 (9.4% eyes (P = 0.001, visual field defects were seen in eight (6.3% eyes (P = 0.0412, and optic disc abnormalities were observed in six (4.7% (P = 0.013 eyes. Color vision abnormalities were noted in 16 (12.6% eyes (P = 0.003, four eyes showed impairment in red-green color perception, and the others showed impairment in blue-yellow color perception as well. Patients with ocular symptoms were advised to stop ethambutol and they showed improvement in visual acuity after follow up of one to two months. The overall outcome of treatment was not affected by discontinuation of ethambutol in these patients. Conclusion: Ethambutol when taken according to program could cause ocular toxicity. The early recognition of ocular symptoms is important to prevent unnecessary delay in diagnosis and probable irreversible visual loss.

  1. Involving children in cooking activities: A potential strategy for directing food choices toward novel foods containing vegetables.

    Science.gov (United States)

    Allirot, Xavier; da Quinta, Noelia; Chokupermal, Krithika; Urdaneta, Elena

    2016-08-01

    Involving children in cooking has been suggested as a strategy to improve dietary habits in childhood. Interventions in schools including cooking, gardening and tasting activities have showed promising results. Several cross-sectional surveys demonstrated associations between frequency of involvement in food preparation and better diet quality. However, experimental studies confirming the beneficial effect of cooking on food choices in children are missing from the literature. The objective of the present study was to assess the effect of involving children in cooking on their willingness to taste novel foods, food intake, liking and hunger. A between-subject experiment was conducted with 137 children between 7 and 11 years old. 69 children (COOK group) participated in the preparation of three unfamiliar foods containing vegetables: apple/beetroot juice, zucchini tortilla sandwich and spinach cookies. 68 children (CONTROL group) participated, instead, in a creative workshop. Afterwards, the children were invited to choose, for an afternoon snack, between three familiar vs. unfamiliar foods: orange vs. apple/beetroot juice, potato vs. zucchini tortilla sandwich and chocolate vs. spinach cookie. The mean number of unfamiliar foods chosen per child was higher in the COOK vs. CONTROL group (P = 0.037). The overall willingness to taste the unfamiliar foods was also higher in the COOK group (P = 0.011). The liking for the whole afternoon snack (P = 0.034), for 2 of 3 unfamiliar foods and for 1 of 3 familiar foods was higher in the COOK group (P food intake and hunger/satiety scores. This study demonstrated that involving children in cooking can increase their willingness to taste novel foods and direct food choices towards foods containing vegetables. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Analysis of Fundus Fluorescein Angiogram Based on the Hessian Matrix of Directional Curvelet Sub-bands and Distance Regularized Level Set Evolution.

    Science.gov (United States)

    Soltanipour, Asieh; Sadri, Saeed; Rabbani, Hossein; Akhlaghi, Mohammad Reza

    2015-01-01

    This paper presents a new procedure for automatic extraction of the blood vessels and optic disk (OD) in fundus fluorescein angiogram (FFA). In order to extract blood vessel centerlines, the algorithm of vessel extraction starts with the analysis of directional images resulting from sub-bands of fast discrete curvelet transform (FDCT) in the similar directions and different scales. For this purpose, each directional image is processed by using information of the first order derivative and eigenvalues obtained from the Hessian matrix. The final vessel segmentation is obtained using a simple region growing algorithm iteratively, which merges centerline images with the contents of images resulting from modified top-hat transform followed by bit plane slicing. After extracting blood vessels from FFA image, candidates regions for OD are enhanced by removing blood vessels from the FFA image, using multi-structure elements morphology, and modification of FDCT coefficients. Then, canny edge detector and Hough transform are applied to the reconstructed image to extract the boundary of candidate regions. At the next step, the information of the main arc of the retinal vessels surrounding the OD region is used to extract the actual location of the OD. Finally, the OD boundary is detected by applying distance regularized level set evolution. The proposed method was tested on the FFA images from angiography unit of Isfahan Feiz Hospital, containing 70 FFA images from different diabetic retinopathy stages. The experimental results show the accuracy more than 93% for vessel segmentation and more than 87% for OD boundary extraction.

  3. The Development of Low-Cost Airlines and Tourism as a Competitiveness Complementor: Effects, Evolution and Strategies

    Directory of Open Access Journals (Sweden)

    Luis Moreno

    2015-12-01

    Full Text Available This paper addresses the relationship between the development of the airline industry and tourism. On the one hand, air transport has triggered the growth of tourism throughout the world, while, on the other hand, tourism has acted as a complementary product for developing new flight routes. This process has intensified with the emergence of low-cost carriers. A profound change has been observed in companies’ strategy to adapt to the demands of this type of market. To conduct this study, a review of the existing literature related to tourism and lowcost carriers was carried out. To conclude, an analysis of the positioning and price-fixing strategies of low-cost airlines operating on some of the most important tourist routes in Europe was performed. The results indicate different level of fares among the five companies in the sample, especially between Ryanair and easyJet, but similar pricing behaviour on the routes studied.

  4. Cellular scanning strategy for selective laser melting: Evolution of optimal grid-based scanning path & parametric approach to thermal homogeneity

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Tutum, Cem Celal; Hattel, Jesper Henri

    2013-01-01

    Selective laser melting, as a rapid manufacturing technology, is uniquely poised to enforce a paradigm shift in the manufacturing industry by eliminating the gap between job- and batch-production techniques. Products from this process, however, tend to show an increased amount of defects such as ...... strategy has been developed for processing the standard sample, one unit cell at a time, using genetic algorithms, with an objective of reducing thermal asymmetries. © 2013 SPIE....

  5. Evolution of Rural Livelihood Strategies in a Remote Sino-Mongolian Border Area: A Cross-Country Analysis

    Directory of Open Access Journals (Sweden)

    Munkhnasan Tsvegemed

    2018-03-01

    Full Text Available Ecologically sound natural resources management is still the backbone of rural livelihoods in many regions of the world. The Altai-Dzungarian region between China and Mongolia constitutes an ideal site to study how political, economic, infrastructural, and cultural differences affect rural livelihoods. Structured semi-quantitative interviews were conducted with 483 households on both sides to characterise their current livelihood strategies and assess the importance of the various activities for the households’ current socio-economic situation by means of the categorical principal component and two-step cluster analysis. In total, four livelihood clusters were identified across both regions, whereby one cluster was only present in Mongolia. In general, all clusters mirrored the transition from almost pure pastoralist to agro-pastoralist livelihood strategies. While animal husbandry was more common in Mongolia and crop farming more common in China, most households in both countries pursued a rather mixed approach. The composition of the herds, as well as the richness and diversity of the livestock species, differed significantly between the countries and was generally higher in Mongolia. Supplementary feedstuff and pesticide and fertiliser use were higher in China, along with diversification of produces. Our analysis indicates that until very recently the livelihood strategies on both sides of the border were the same, manifesting in the fact that we can define three identical clusters across countries (environment factor even though there are slight differences in land, livestock and asset endowment.

  6. Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E.; Carter, Patrick A.; Garland, Theodore

    2015-01-01

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance–covariance matrix (G). Yet knowledge of G in a population experiencing new or altered selection is not sufficient to predict selection response because G itself evolves in ways that are poorly understood. We experimentally evaluated changes in G when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

  7. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. © 2015 The Author(s).

  8. Direct view on the phase evolution in individual LiFePO4 nanoparticles during Li-ion battery cycling.

    Science.gov (United States)

    Zhang, Xiaoyu; van Hulzen, Martijn; Singh, Deepak P; Brownrigg, Alex; Wright, Jonathan P; van Dijk, Niels H; Wagemaker, Marnix

    2015-09-23

    Phase transitions in Li-ion electrode materials during (dis)charge are decisive for battery performance, limiting high-rate capabilities and playing a crucial role in the cycle life of Li-ion batteries. However, the difficulty to probe the phase nucleation and growth in individual grains is hindering fundamental understanding and progress. Here we use synchrotron microbeam diffraction to disclose the cycling rate-dependent phase transition mechanism within individual particles of LiFePO4, a key Li-ion electrode material. At low (dis)charge rates well-defined nanometer thin plate-shaped domains co-exist and transform much slower and concurrent as compared with the commonly assumed mosaic transformation mechanism. As the (dis)charge rate increases phase boundaries become diffuse speeding up the transformation rates of individual grains. Direct observation of the transformation of individual grains reveals that local current densities significantly differ from what has previously been assumed, giving new insights in the working of Li-ion battery electrodes and their potential improvements.

  9. Estrutura e estratégia: evolução de paradigmas Structure and strategy: evolution of paradigms

    Directory of Open Access Journals (Sweden)

    Fernando Carvalho de Almeida

    2006-06-01

    Full Text Available O presente trabalho analisa as relações de interdependência existentes entre a estrutura da empresa e as estratégias a serem implementadas. É feita uma breve revisão da literatura sobre estratégia, administração estratégica e as diversas formas de conduzir a implementação das que se apresentam como as mais adequadas à consecução dos objetivos organizacionais. Foram analisados os modelos tradicionais de estrutura organizacional, bem como as vantagens e desvantagens estratégicas que cada um apresenta. Por fim, foram estudadas as abordagens de diferentes autores sobre as relações de interdependência entre a estrutura da empresa e as suas estratégias. Em conclusão, verifica-se que, embora as estratégias da empresa possam ser fixadas a partir da análise da sua estrutura organizacional, dos seus pontos fortes e fracos, esta atitude nem sempre é viável. Numa época em que as tecnologias evoluem de forma extremamente rápida e a competitividade se acelera em nível global, tornam-se necessárias estruturas organizacionais flexíveis, que possam modificar-se rapidamente, para atender às estratégias capazes de permitir a adequada inserção da empresa em um ambiente externo extremamente volátil.The interdependent relations that exist between the structure of an organization and the organizational strategies to be implemented were analyzed. A review was made of literature on strategy, strategic management and methods of implementing strategies appropriate for organization objectives. Traditional models of organization structures were then analyzed as well as the inherent strategic advantages and disadvantages. Then the approach of various authors to these interdependent relations was studied. It was concluded that although organizational strategy can be established by analyzing organization structure as well as the strong and weak aspects involved, this is not always feasible. With fast paced technologies and sharpening global

  10. The relevance of team characteristics and team directed strategies in the implementation of nursing innovations : A literature review

    NARCIS (Netherlands)

    Theo van Achterberg; Joke Mintjes; G. Holleman; E. Poot

    2009-01-01

    Implementation of innovations is a complex and intensive procedure in which different strategies can be successful. In nursing, strategies often focus on intrinsic motivation, competencies and attitudes of individual nurses while ignoring the social context. Since nurses often work in teams,

  11. Evolution of flavone synthase I from parsley flavanone 3beta-hydroxylase by site-directed mutagenesis.

    Science.gov (United States)

    Gebhardt, Yvonne Helen; Witte, Simone; Steuber, Holger; Matern, Ulrich; Martens, Stefan

    2007-07-01

    Flavanone 3beta-hydroxylase (FHT) and flavone synthase I (FNS I) are 2-oxoglutarate-dependent dioxygenases with 80% sequence identity, which catalyze distinct reactions in flavonoid biosynthesis. However, FNS I has been reported exclusively from a few Apiaceae species, whereas FHTs are more abundant. Domain-swapping experiments joining the N terminus of parsley (Petroselinum crispum) FHT with the C terminus of parsley FNS I and vice versa revealed that the C-terminal portion is not essential for FNS I activity. Sequence alignments identified 26 amino acid substitutions conserved in FHT versus FNS I genes. Homology modeling, based on the related anthocyanidin synthase structure, assigned seven of these amino acids (FHT/FNS I, M106T, I115T, V116I, I131F, D195E, V200I, L215V, and K216R) to the active site. Accordingly, FHT was modified by site-directed mutagenesis, creating mutants encoding from one to seven substitutions, which were expressed in yeast (Saccharomyces cerevisiae) for FNS I and FHT assays. The exchange I131F in combination with either M106T and D195E or L215V and K216R replacements was sufficient to confer some FNS I side activity. Introduction of all seven FNS I substitutions into the FHT sequence, however, caused a nearly complete change in enzyme activity from FHT to FNS I. Both FHT and FNS I were proposed to initially withdraw the beta-face-configured hydrogen from carbon-3 of the naringenin substrate. Our results suggest that the 7-fold substitution affects the orientation of the substrate in the active-site pocket such that this is followed by syn-elimination of hydrogen from carbon-2 (FNS I reaction) rather than the rebound hydroxylation of carbon-3 (FHT reaction).

  12. Development of a model for optimisation of a power plant mix by means of evolution strategy; Modellentwicklung zur Kraftwerksparkoptimierung mit Hilfe von Evolutionsstrategien

    Energy Technology Data Exchange (ETDEWEB)

    Roth, Hans

    2008-09-17

    Within the scope of this thesis a model based on evolution strategy is depicted, which optimises the upgrade of an existing power plant mix. In doing so the optimisation problem is divided in two sections covering the building of new power plants as well as their ideal usage within the persisting power plant mix. The building of new power plants is optimised by means of mutations, while their ideal usage is specified by a heuristic classification according to the merit order of the power plant mix. By applying a residual yearly load curve the consumer load can be modelled, incorporating the impact of fluctuating power generation and its probability of occurrence. Power plant failures and the duration of revisions are adequately considered by means of a power reduction factor. The optimisation furthermore accommodates a limiting threshold for yearly carbon dioxide emissions as well as a premature decommissioning of power plants. (orig.)

  13. Five-year evolution of reperfusion strategies and early mortality in patients with ST-segment elevation myocardial infarction in France.

    Science.gov (United States)

    El Khoury, Carlos; Bochaton, Thomas; Flocard, Elodie; Serre, Patrice; Tomasevic, Danka; Mewton, Nathan; Bonnefoy-Cudraz, Eric

    2017-10-01

    To assess 5-year evolutions in reperfusion strategies and early mortality in patients with ST-segment elevation myocardial infarction. Using data from the French RESCUe network, we studied patients with ST-segment elevation myocardial infarction treated in mobile intensive care units between 2009 and 2013. Among 2418 patients (median age 62 years; 78.5% male), 2119 (87.6%) underwent primary percutaneous coronary intervention and 299 (12.4%) pre-hospital thrombolysis (94.0% of whom went on to undergo percutaneous coronary intervention). Use of primary percutaneous coronary intervention increased from 78.4% in 2009 to 95.9% in 2013 ( P trend 90 minutes delay group (83.0% in 2009 to 97.7% in 2013; P trend <0.001 versus 34.1% in 2009 to 79.2% in 2013; P trend <0.001). In-hospital (4-6%) and 30-day (6-8%) mortalities remained stable from 2009 to 2013. In the RESCUe network, the use of primary percutaneous coronary intervention increased from 2009 to 2013, in line with guidelines, but there was no evolution in early mortality.

  14. Direct Measurements of the Evolution and Impact of Sediment Density Flows as they Pass Through Monterey Submarine Canyon, Offshore California

    Science.gov (United States)

    Paull, C. K.; Talling, P.; Maier, K. L.; Parsons, D. R.; Xu, J.; Caress, D. W.; Gwiazda, R.; Lundsten, E. M.; Anderson, K.; Barry, J.; Chaffey, M. R.; O'Reilly, T. C.; Rosenberger, K. J.; Gales, J. A.; McGann, M.; McCann, M. P.; Simmons, S.; Sumner, E.

    2017-12-01

    Sediment density flows flushing through submarine canyons carry globally significant amounts of material into the deep sea to form many of the largest sediment accumulations on Earth. Despite their global significance, these flows remain poorly understood because they have rarely been directly measured. Here we provide an initial overview of the recently completed Coordinated Canyon Experiment (CCE), which was undertaken specifically to provide detailed measurements of sediment density flows and their impact on seafloor morphology and sedimentology. No previous study has deployed as extensive an array of monitoring sensors along a turbidity current pathway. During the 18 months of the CCE, at least 15 sediment density flows were recorded within the axis of Monterey Canyon. Because no external triggers (i.e., earthquakes or floods) correlate with these flows, they must have originated as failures in the canyon floor or canyon flanks. Three flows ignited and ran out for > 50 km from water depths of 1,860 m, reaching velocities up to 8.1 m/s. The rest of the flows died out within the array. During these events, large objects on or in the canyon floor were displaced substantial distances downslope, including a 7.1 km downslope movement of an entire mooring; a 4.6 km displacement of an 860 kg instrument frame followed by repeated down canyon displacements of this same frame after it was entombed in sediment; and multiple depth changes of man-made boulders containing acceleration and pressure sensors. During this same time interval the canyon floor was mapped six times with autonomous underwater vehicles covering the canyon thalweg at the upper and lower end of the instrument array (200-540 and 1350-1880 m water depths). The repeated mapping surveys reveal that flows caused +3 to -3 m bathymetric changes within a continuous clearly defined 200 m wide swath running along the canyon axis in 540 m water depth. This study shows that sediment density flows caused massive

  15. Using a linked data approach to aid development of a metadata portal to support Marine Strategy Framework Directive (MSFD) implementation

    Science.gov (United States)

    Wood, Chris

    2016-04-01

    Under the Marine Strategy Framework Directive (MSFD), EU Member States are mandated to achieve or maintain 'Good Environmental Status' (GES) in their marine areas by 2020, through a series of Programme of Measures (PoMs). The Celtic Seas Partnership (CSP), an EU LIFE+ project, aims to support policy makers, special-interest groups, users of the marine environment, and other interested stakeholders on MSFD implementation in the Celtic Seas geographical area. As part of this support, a metadata portal has been built to provide a signposting service to datasets that are relevant to MSFD within the Celtic Seas. To ensure that the metadata has the widest possible reach, a linked data approach was employed to construct the database. Although the metadata are stored in a traditional RDBS, the metadata are exposed as linked data via the D2RQ platform, allowing virtual RDF graphs to be generated. SPARQL queries can be executed against the end-point allowing any user to manipulate the metadata. D2RQ's mapping language, based on turtle, was used to map a wide range of relevant ontologies to the metadata (e.g. The Provenance Ontology (prov-o), Ocean Data Ontology (odo), Dublin Core Elements and Terms (dc & dcterms), Friend of a Friend (foaf), and Geospatial ontologies (geo)) allowing users to browse the metadata, either via SPARQL queries or by using D2RQ's HTML interface. The metadata were further enhanced by mapping relevant parameters to the NERC Vocabulary Server, itself built on a SPARQL endpoint. Additionally, a custom web front-end was built to enable users to browse the metadata and express queries through an intuitive graphical user interface that requires no prior knowledge of SPARQL. As well as providing means to browse the data via MSFD-related parameters (Descriptor, Criteria, and Indicator), the metadata records include the dataset's country of origin, the list of organisations involved in the management of the data, and links to any relevant INSPIRE

  16. Highly efficient direct Z-scheme WO3/CdS-diethylenetriamine photocatalyst and its enhanced photocatalytic H2 evolution under visible light irradiation

    Science.gov (United States)

    Hu, Taiping; Li, Pengfei; Zhang, Jinfeng; Liang, Changhao; Dai, Kai

    2018-06-01

    Cadmium sulfide (CdS) has demonstrated great promise in artificial photocataytic hydrogen (H2) production. However, the serious photocorrosion hinders its effective interaction and real-life application. In this work, a typical direct Z-scheme WO3/CdS-diethylenetriamine (CdS-DETA) composite has been designed via facile in-situ solvothermal method, which exhibits excellent H2 production properties in visible light region. In this system, the inorganic-organic CdS-DETA nanobelts (NBs) possess enough active sites and large surface area for the encouraging nanojunction structure information. Furthermore, we also systematically calculated energy band structure and investigated charge transfer of the WO3/CdS-DETA by PL and photocurrent test, the results demonstrated that the suitable band gap matching between CdS-DETA and WO3 and high redox potential improve the separation of photogenerated holes and electrons, restraining intrinsic photocorrosion of CdS as well as improving the photocatalytic activity. 5%WO3/CdS-DETA presented the most outstanding H2 evolution rate (15522 μmol g-1 h-1), which is twice higher than that of pure CdS-DETA. WO3/CdS-DETA composites also presented high stability after three recycle H2 production experiment. Finally, direct Z-scheme photocatalytic mechanism is calculated.

  17. Direct evidence for a systematic evolution of optical band gap and local disorder in Ag, in doped Sb{sub 2}Te phase change material

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Krishna Dayal; Sahu, Smriti [Discipline of Electrical Engineering, Indian Institute of Technology Indore (India); Manivannan, Anbarasu [Discipline of Electrical Engineering, Indian Institute of Technology Indore (India); Metallurgical Engineering and Materials Science, Indian Institute of Technology Indore, Indore (India); Deshpande, Uday Prabhakarrao [UGC-DAE Consortium for Scientific Research, Indore (India)

    2017-12-15

    Rapid and reversible switching properties of Ag, In doped Sb{sub 2}Te (AIST) phase change material is widely used in re-writable optical data storage applications. We report here a systematic evolution of optical band gap (E{sub g}), local disorder (Tauc parameter, β), and Urbach energy (E{sub U}) of AIST material during amorphous to crystalline transition using in situ UV-Vis-NIR spectroscopy. Unlike GeTe-Sb{sub 2}Te{sub 3} (GST) family, AIST material is found to show unique characteristics as evidenced by the presence of direct forbidden transitions. Crystallization is accompanied by a systematic reduction in E{sub g} from 0.50 eV (as-deposited amorphous at 300 K) to 0.18 eV (crystalline at 300 K). Moreover, decrease in E{sub U} (from 272 to 212 meV) and β is also observed during increasing the temperature in the amorphous phase, revealing direct observation of enhancement of the medium-range order and distortion in short range order, respectively. These findings of optical transition would be helpful for distinguishing the unique behavior of AIST material from GST family. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for the evolution of life history strategies

    Science.gov (United States)

    Durkin, Alanna; Fisher, Charles R.; Cordes, Erik E.

    2017-08-01

    The deep sea is home to many species that have longer life spans than their shallow-water counterparts. This trend is primarily related to the decline in metabolic rates with temperature as depth increases. However, at bathyal depths, the cold-seep vestimentiferan tubeworm species Lamellibrachia luymesi and Seepiophila jonesi reach extremely old ages beyond what is predicted by the simple scaling of life span with body size and temperature. Here, we use individual-based models based on in situ growth rates to show that another species of cold-seep tubeworm found in the Gulf of Mexico, Escarpia laminata, also has an extraordinarily long life span, regularly achieving ages of 100-200 years with some individuals older than 300 years. The distribution of results from individual simulations as well as whole population simulations involving mortality and recruitment rates support these age estimates. The low 0.67% mortality rate measurements from collected populations of E. laminata are similar to mortality rates in L. luymesi and S. jonesi and play a role in evolution of the long life span of cold-seep tubeworms. These results support longevity theory, which states that in the absence of extrinsic mortality threats, natural selection will select for individuals that senesce slower and reproduce continually into their old age.

  19. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Mackey, Tim K

    2016-02-03

    The adoption and use of digital forms of direct-to-consumer advertising (also known as "eDTCA") is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA) notices of violations (NOVs) and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the "disruptive" qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored. © 2016 by Kerman University of Medical Sciences.

  20. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Tim K. Mackey

    2016-04-01

    Full Text Available The adoption and use of digital forms of direct-to-consumer advertising (also known as “eDTCA” is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA notices of violations (NOVs and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the “disruptive” qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored.

  1. Market Imitation and Win-Stay Lose-Shift Strategies Emerge as Unintended Patterns in Market Direction Guesses

    Science.gov (United States)

    Segura, Carlota; Duch, Jordi; Perelló, Josep

    2016-01-01

    Decisions made in our everyday lives are based on a wide variety of information so it is generally very difficult to assess what are the strategies that guide us. Stock market provides a rich environment to study how people make decisions since responding to market uncertainty needs a constant update of these strategies. For this purpose, we run a lab-in-the-field experiment where volunteers are given a controlled set of financial information -based on real data from worldwide financial indices- and they are required to guess whether the market price would go “up” or “down” in each situation. From the data collected we explore basic statistical traits, behavioural biases and emerging strategies. In particular, we detect unintended patterns of behavior through consistent actions, which can be interpreted as Market Imitation and Win-Stay Lose-Shift emerging strategies, with Market Imitation being the most dominant. We also observe that these strategies are affected by external factors: the expert advice, the lack of information or an information overload reinforce the use of these intuitive strategies, while the probability to follow them significantly decreases when subjects spends more time to make a decision. The cohort analysis shows that women and children are more prone to use such strategies although their performance is not undermined. Our results are of interest for better handling clients expectations of trading companies, to avoid behavioural anomalies in financial analysts decisions and to improve not only the design of markets but also the trading digital interfaces where information is set down. Strategies and behavioural biases observed can also be translated into new agent based modelling or stochastic price dynamics to better understand financial bubbles or the effects of asymmetric risk perception to price drops. PMID:27532219

  2. Market Imitation and Win-Stay Lose-Shift Strategies Emerge as Unintended Patterns in Market Direction Guesses.

    Science.gov (United States)

    Gutiérrez-Roig, Mario; Segura, Carlota; Duch, Jordi; Perelló, Josep

    2016-01-01

    Decisions made in our everyday lives are based on a wide variety of information so it is generally very difficult to assess what are the strategies that guide us. Stock market provides a rich environment to study how people make decisions since responding to market uncertainty needs a constant update of these strategies. For this purpose, we run a lab-in-the-field experiment where volunteers are given a controlled set of financial information -based on real data from worldwide financial indices- and they are required to guess whether the market price would go "up" or "down" in each situation. From the data collected we explore basic statistical traits, behavioural biases and emerging strategies. In particular, we detect unintended patterns of behavior through consistent actions, which can be interpreted as Market Imitation and Win-Stay Lose-Shift emerging strategies, with Market Imitation being the most dominant. We also observe that these strategies are affected by external factors: the expert advice, the lack of information or an information overload reinforce the use of these intuitive strategies, while the probability to follow them significantly decreases when subjects spends more time to make a decision. The cohort analysis shows that women and children are more prone to use such strategies although their performance is not undermined. Our results are of interest for better handling clients expectations of trading companies, to avoid behavioural anomalies in financial analysts decisions and to improve not only the design of markets but also the trading digital interfaces where information is set down. Strategies and behavioural biases observed can also be translated into new agent based modelling or stochastic price dynamics to better understand financial bubbles or the effects of asymmetric risk perception to price drops.

  3. Adaptive social learning strategies in temporally and spatially varying environments : how temporal vs. spatial variation, number of cultural traits, and costs of learning influence the evolution of conformist-biased transmission, payoff-biased transmission, and individual learning.

    Science.gov (United States)

    Nakahashi, Wataru; Wakano, Joe Yuichiro; Henrich, Joseph

    2012-12-01

    Long before the origins of agriculture human ancestors had expanded across the globe into an immense variety of environments, from Australian deserts to Siberian tundra. Survival in these environments did not principally depend on genetic adaptations, but instead on evolved learning strategies that permitted the assembly of locally adaptive behavioral repertoires. To develop hypotheses about these learning strategies, we have modeled the evolution of learning strategies to assess what conditions and constraints favor which kinds of strategies. To build on prior work, we focus on clarifying how spatial variability, temporal variability, and the number of cultural traits influence the evolution of four types of strategies: (1) individual learning, (2) unbiased social learning, (3) payoff-biased social learning, and (4) conformist transmission. Using a combination of analytic and simulation methods, we show that spatial-but not temporal-variation strongly favors the emergence of conformist transmission. This effect intensifies when migration rates are relatively high and individual learning is costly. We also show that increasing the number of cultural traits above two favors the evolution of conformist transmission, which suggests that the assumption of only two traits in many models has been conservative. We close by discussing how (1) spatial variability represents only one way of introducing the low-level, nonadaptive phenotypic trait variation that so favors conformist transmission, the other obvious way being learning errors, and (2) our findings apply to the evolution of conformist transmission in social interactions. Throughout we emphasize how our models generate empirical predictions suitable for laboratory testing.

  4. Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.

    Science.gov (United States)

    Sahn, James J; Granger, Brett A; Martin, Stephen F

    2014-10-21

    A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.

  5. The strategies of European energy operators. Which strategic and capitalistic evolutions for the sector on a medium term?

    International Nuclear Information System (INIS)

    2012-11-01

    This article presents the content of a market study which aimed at describing the current regulatory context of energy markets in Europe and the degree of openness to competition, at analysing all figures concerning electricity and natural gas in different countries (production, consumption, balance of trade), at analysing development strategies of electricity providers and gas operators and at assessing their strengths and weaknesses, at comparing financial performance of leader groups and at assessing their financial flexibility, and at anticipating the reconfiguration of the sector on a medium term. Fifteen energy companies or operators have been analysed: Centrica, CEZ, E.ON, EDF, EDP, Enel, ENI, Fortum, Gas Natural, GDF Suez, Iberdrola, RWE, SSE, Vattenfall, Verbund

  6. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

    Science.gov (United States)

    Mendichovszky, I A; Priest, A N; Bowden, D J; Hunter, S; Joubert, I; Hilborne, S; Graves, M J; Baglin, T; Lomas, D J

    2017-06-01

    Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. • MRI can distinguish between acute and evolving or chronic lower limb DVT • Two advanced MRI techniques can follow the evolution of lower limb DVT • MRI could be used to avoid an incorrect diagnosis of recurrent DVT • MRI could help avoid the risks and complications of lifelong anticoagulation therapy.

  7. Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies

    Energy Technology Data Exchange (ETDEWEB)

    Loebel, U. [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States); Hwang, S.; Edwards, A.; Patay, Z. [St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States); Li, Y.; Li, X. [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Broniscer, A. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Pediatrics, Memphis, TN (United States)

    2016-10-15

    Based on clinical observations, we hypothesized that in infiltrative high-grade brainstem neoplasms, such as diffuse intrinsic pontine glioma (DIPG), longitudinal metabolic evaluation of the tumor by magnetic resonance spectroscopy (MRS) may be more accurate than volumetric data for monitoring the tumor's biological evolution during standard treatment. We evaluated longitudinal MRS data and corresponding tumor volumes of 31 children with DIPG. We statistically analyzed correlations between tumor volume and ratios of Cho/NAA, Cho/Cr, and NAA/Cr at key time points during the course of the disease through the end of the progression-free survival period. By the end of RT, tumor volume had significantly decreased from the baseline (P <.0001) and remained decreased through the last available follow-up magnetic resonance imaging study (P =.007632). However, the metabolic profile of the tumor tissue (Cho/Cr, NAA/Cr, and Cho/NAA ratios) did not change significantly over time. Our data show that longitudinal tumor volume and metabolic profile changes are dissociated in patients with DIPG during progression-free survival. Volume changes, therefore, may not accurately reflect treatment-related changes in tumor burden. This study adds to the existing body of evidence that the value of conventional MRI metrics, including volumetric data, needs to be reevaluated critically and, in infiltrative tumors in particular, may not be useful as study end-points in clinical trials. We submit that advanced quantitative MRI data, including robust, MRS-based metabolic ratios and diffusion and perfusion metrics, may be better surrogate markers of key end-points in clinical trials. (orig.)

  8. The cook, the thief, his wife and her lover: on the evolution of the human reproductive strategy.

    Science.gov (United States)

    Schuiling, G A

    2003-12-01

    Human reproductive strategy differs from that of most other mammals, including Apes such as the closely related chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). For example, humans, although basically polygamic, exhibit a strong tendency to (serial) monogamy and--very rare for a mammal--provide biparental care. Moreover, humans are (almost) permanently willing to mate but, in contrast to other species, do so only in private. Unlike chimpanzees and bonobos, the human female exhibits no external signs of ovulation; rather a number of bodily features, e.g. permanently swollen milk glands and the quality of skin and hair, indicate fitness to breed. Human males also exhibit qualities that are rare among mammals: fertile males can be in the company of fertile females without sex being an imperative--although the awareness of sexuality is generally omnipresent. Moreover, unlike most other Apes, human males can cooperate in large groups, in spite of their polygynic inclination and their tendency to compete with each other for access to females. This capacity probably evolved in response to the necessity to acquire food, in particular meat, which was difficult to obtain by a single man. But life in large, complex, multi-male, multi-female groups places great demands on the members' social skills and, to be able to meet these demands, a large, sophisticated brain (neocortex) is needed. Food (and in its wake, cooking) probably forced man to live in ever-larger groups and to evolve the capacity to cooperate. This, in its turn, drove man's present-days psychosocial (emotional and intellectual) make-up. But for this to evolve, an adaptation of reproductive strategy was a conditio sine qua non.

  9. Supercapacitor electrodes by direct growth of multi-walled carbon nanotubes on Al: a study of performance versus layer growth evolution

    International Nuclear Information System (INIS)

    Zhao, Fu; Vicenzo, Antonello; Hashempour, Mazdak; Bestetti, Massimiliano

    2014-01-01

    Supercapacitor electrodes were fabricated by direct growth of multi-walled carbon nanotubes (CNTs) on Al current collectors via a chemical vapor deposition process in the presence of a spin-coated Co-Mo catalyst. A detailed study of the dependence of the CNT layer structure and thickness on growth time set the basis for the assessment of supercapacitors assembled with the CNTs/Al electrodes. As the main features of the layer growth evolution, an increase in the population of finer CNTs and a shift from a random entanglement to a rough vertical alignment of nanotubes were noted with proceeding growth. The growth time influence on the performance of supercapacitors was in fact apparent. Particularly, the specific capacitance of CNTs/Al electrodes in 0.5 M K 2 SO 4 aqueous electrolyte increased from 35 to 80 F g −1 as the CNT layer thickness varied from 20 to 60 μm, with a concurrent loss in rate capability (knee frequency from 1 kHz to 60 Hz). The latter was excellent in general, arguably due to both a fast ion transport through the interconnected CNT network and a negligible contribution of the active layer/current collector contact to the equivalent series resistance (0.15–0.22 mΩ g), a distinct advantage of the direct growth fabrication method. Overall, a relatively simple process of direct growth of CNTs on Al foils is shown to be an effective method to fabricate supercapacitor electrodes, notably in the absence of special measures and processing steps finalized to a tight control of nanotubes growth and organization

  10. Design, monitoring and evaluation of a direct payments approach for an ecotourism strategy to reduce illegal hunting and trade of wildlife in Lao PDR

    Science.gov (United States)

    Johnson, Arlyne; Duangdala, Sivilay; Hansel, Troy

    2018-01-01

    Ecotourism as a strategy for achieving biodiversity conservation often results in limited conservation impact relative to its investment and revenue return. In cases where an ecotourism strategy has been used, projects are frequently criticized for not providing sufficient evidence on how the strategy has reduced threats or improved the status of the biodiversity it purports to protect. In Lao PDR, revenue from ecotourism has not been directly linked to or dependent on improvements in biodiversity and there is no evidence that ecotourism enterprises have contributed to conservation. In other developing countries, direct payments through explicit contracts in return for ecosystem services have been proposed as a more cost-effective means for achieving conservation, although further research is needed to evaluate the impact of this approach. To address this need, a new model was tested in the Nam Et-Phou Louey National Protected Area (NPA) in Lao PDR using a direct payments approach to create ecotourism incentives for villagers to increase wildlife populations. Over a four-year period, we monitored along a theory of change to evaluate assumptions about the linkages between intermediate results and biological outcomes. Preliminary results show a negative correlation between ecotourism benefits and hunting infractions in target villages; no increase in hunting sign in the ecotourism sector of the NPA relative to a three-fold increase in hunting sign across the NPA’s non-tourism sectors; and an overall increase in wildlife sightings. This case provides key lessons on the design of a direct payments approach for an ecotourism strategy, including how to combine threat monitoring and data on wildlife sightings to evaluate strategy effectiveness, on setting rates for wildlife sightings and village fees, and the utility of the approach for protecting very rare species. PMID:29489821

  11. Design, monitoring and evaluation of a direct payments approach for an ecotourism strategy to reduce illegal hunting and trade of wildlife in Lao PDR.

    Science.gov (United States)

    Eshoo, Paul Frederick; Johnson, Arlyne; Duangdala, Sivilay; Hansel, Troy

    2018-01-01

    Ecotourism as a strategy for achieving biodiversity conservation often results in limited conservation impact relative to its investment and revenue return. In cases where an ecotourism strategy has been used, projects are frequently criticized for not providing sufficient evidence on how the strategy has reduced threats or improved the status of the biodiversity it purports to protect. In Lao PDR, revenue from ecotourism has not been directly linked to or dependent on improvements in biodiversity and there is no evidence that ecotourism enterprises have contributed to conservation. In other developing countries, direct payments through explicit contracts in return for ecosystem services have been proposed as a more cost-effective means for achieving conservation, although further research is needed to evaluate the impact of this approach. To address this need, a new model was tested in the Nam Et-Phou Louey National Protected Area (NPA) in Lao PDR using a direct payments approach to create ecotourism incentives for villagers to increase wildlife populations. Over a four-year period, we monitored along a theory of change to evaluate assumptions about the linkages between intermediate results and biological outcomes. Preliminary results show a negative correlation between ecotourism benefits and hunting infractions in target villages; no increase in hunting sign in the ecotourism sector of the NPA relative to a three-fold increase in hunting sign across the NPA's non-tourism sectors; and an overall increase in wildlife sightings. This case provides key lessons on the design of a direct payments approach for an ecotourism strategy, including how to combine threat monitoring and data on wildlife sightings to evaluate strategy effectiveness, on setting rates for wildlife sightings and village fees, and the utility of the approach for protecting very rare species.

  12. Modified Covariance Matrix Adaptation – Evolution Strategy algorithm for constrained optimization under uncertainty, application to rocket design

    Directory of Open Access Journals (Sweden)

    Chocat Rudy

    2015-01-01

    Full Text Available The design of complex systems often induces a constrained optimization problem under uncertainty. An adaptation of CMA-ES(λ, μ optimization algorithm is proposed in order to efficiently handle the constraints in the presence of noise. The update mechanisms of the parametrized distribution used to generate the candidate solutions are modified. The constraint handling method allows to reduce the semi-principal axes of the probable research ellipsoid in the directions violating the constraints. The proposed approach is compared to existing approaches on three analytic optimization problems to highlight the efficiency and the robustness of the algorithm. The proposed method is used to design a two stage solid propulsion launch vehicle.

  13. Directed evolution of adaptive traits

    Science.gov (United States)

    As a species, switchgrass is adapted to an amazingly broad range of environments, spanning hardiness zones ranging from HZ3 to HZ9 (Canada to Mexico), from the mid-grass prairie to the Atlantic Seaboard, from sandy soils to heavy clay soils, from acid to alkaline soils, and from wetland to dryland h...

  14. "Gone are the days of mass-media marketing plans and short term customer relationships": tobacco industry direct mail and database marketing strategies.

    Science.gov (United States)

    Lewis, M Jane; Ling, Pamela M

    2016-07-01

    As limitations on traditional marketing tactics and scrutiny by tobacco control have increased, the tobacco industry has benefited from direct mail marketing which transmits marketing messages directly to carefully targeted consumers utilising extensive custom consumer databases. However, research in these areas has been limited. This is the first study to examine the development, purposes and extent of direct mail and customer databases. We examined direct mail and database marketing by RJ Reynolds and Philip Morris utilising internal tobacco industry documents from the Legacy Tobacco Document Library employing standard document research techniques. Direct mail marketing utilising industry databases began in the 1970s and grew from the need for a promotional strategy to deal with declining smoking rates, growing numbers of products and a cluttered media landscape. Both RJ Reynolds and Philip Morris started with existing commercial consumer mailing lists, but subsequently decided to build their own databases of smokers' names, addresses, brand preferences, purchase patterns, interests and activities. By the mid-1990s both RJ Reynolds and Philip Morris databases contained at least 30 million smokers' names each. These companies valued direct mail/database marketing's flexibility, efficiency and unique ability to deliver specific messages to particular groups as well as direct mail's limited visibility to tobacco control, public health and regulators. Database marketing is an important and increasingly sophisticated tobacco marketing strategy. Additional research is needed on the prevalence of receipt and exposure to direct mail items and their influence on receivers' perceptions and smoking behaviours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. “Gone are the days of mass-media marketing plans and short term customer relationships”: tobacco industry direct mail and database marketing strategies

    Science.gov (United States)

    Lewis, M Jane; Ling, Pamela M

    2015-01-01

    Background As limitations on traditional marketing tactics and scrutiny by tobacco control have increased, the tobacco industry has benefited from direct mail marketing which transmits marketing messages directly to carefully targeted consumers utilising extensive custom consumer databases. However, research in these areas has been limited. This is the first study to examine the development, purposes and extent of direct mail and customer databases. Methods We examined direct mail and database marketing by RJ Reynolds and Philip Morris utilising internal tobacco industry documents from the Legacy Tobacco Document Library employing standard document research techniques. Results Direct mail marketing utilising industry databases began in the 1970s and grew from the need for a promotional strategy to deal with declining smoking rates, growing numbers of products and a cluttered media landscape. Both RJ Reynolds and Philip Morris started with existing commercial consumer mailing lists, but subsequently decided to build their own databases of smokers’ names, addresses, brand preferences, purchase patterns, interests and activities. By the mid-1990s both RJ Reynolds and Philip Morris databases contained at least 30 million smokers’ names each. These companies valued direct mail/database marketing’s flexibility, efficiency and unique ability to deliver specific messages to particular groups as well as direct mail’s limited visibility to tobacco control, public health and regulators. Conclusions Database marketing is an important and increasingly sophisticated tobacco marketing strategy. Additional research is needed on the prevalence of receipt and exposure to direct mail items and their influence on receivers’ perceptions and smoking behaviours. PMID:26243810

  16. Contemporary Directions in Theories and Psychotherapeutic Strategies in Treatment of Personality Disorders: Relation to Level of Personality Functioning

    DEFF Research Database (Denmark)

    Simonsen, Sebastian; Simonsen, Erik

    2014-01-01

    In this commentary on treatment strategies for personality disorders, we analyze each of the cases and the problem of low motivation in terms of how they fit with the Level of Personality Functioning scale. We then show how patients vary in terms of both level and breadth of pathology. Three...

  17. A general design strategy for block copolymer directed self-assembly patterning of integrated circuits contact holes using an alphabet approach.

    Science.gov (United States)

    Yi, He; Bao, Xin-Yu; Tiberio, Richard; Wong, H-S Philip

    2015-02-11

    Directed self-assembly (DSA) is a promising lithography candidate for technology nodes beyond 14 nm. Researchers have shown contact hole patterning for random logic circuits using DSA with small physical templates. This paper introduces an alphabet approach that uses a minimal set of small physical templates to pattern all contacts configurations on integrated circuits. We illustrate, through experiments, a general and scalable template design strategy that links the DSA material properties to the technology node requirements.

  18. The strategy of alternate direction adapted to a coarse mesh method for the solution of neutron diffusion problems

    International Nuclear Information System (INIS)

    Watson, F.V.

    1982-01-01

    An adaptation of the alternate direction method for coarse mesh calculation, is presented. The algorithm is applicable to two-and three dimensional problems, the last being the more interesting one. (E.G.) [pt

  19. Strategies to meet the requirements of the Nitrates Directive on arable and field vegetable farms in The Netherlands

    NARCIS (Netherlands)

    Langeveld, J.W.A.

    2003-01-01

    Intensive fertilisation practices in the Netherlands make it cumbersome to comply with the EU Nitrate Directive. Over the years, government has adopted increasingly strict environmental legislation, including the farm gate balance system MINAS (MINeral Accounting System) and a compulsory manure

  20. Enantioselective Direct α-Amination of Aldehydes via a Photoredox Mechanism: A Strategy for Asymmetric Amine Fragment Coupling

    OpenAIRE

    Cecere, Giuseppe; Koenig, Christian M.; Alleva, Jennifer L.; MacMillan, David W. C.

    2013-01-01

    The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated, nitrogen-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Important...

  1. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Mendichovszky, I.A.; Lomas, D.J. [Addenbrooke' s Hospital, Department of Radiology, Cambridge (United Kingdom); University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Priest, A.N.; Bowden, D.J.; Hunter, S.; Joubert, I.; Hilborne, S.; Graves, M.J. [Addenbrooke' s Hospital, Department of Radiology, Cambridge (United Kingdom); Baglin, T. [Addenbrooke' s Hospital, Department of Haematology, Cambridge (United Kingdom)

    2017-06-15

    Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. (orig.)

  2. In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

    Science.gov (United States)

    Pick, J L; Hutter, P; Tschirren, B

    2016-06-01

    Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.

  3. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study

    International Nuclear Information System (INIS)

    Mendichovszky, I.A.; Lomas, D.J.; Priest, A.N.; Bowden, D.J.; Hunter, S.; Joubert, I.; Hilborne, S.; Graves, M.J.; Baglin, T.

    2017-01-01

    Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. (orig.)

  4. In-situ exploration of Venus on a global scale : direct measurements of origins and evolution, meterology, dynamics, and chemistry by a long-duration aerial science station

    Science.gov (United States)

    Baines, Kevin H.; Atreya, Sushi; Carlson, Robert W.; Chutjian, Ara; Crisp, David; Hall, Jeffrey L.; Jones, Dayton L.; Kerzhanovich, Victor V.; Limaye, Sanjay S.

    2005-01-01

    Drifting in the strong winds of Venus under benign Earth-like temperature and pressure conditions, an instrumented balloon-borne science station presents a viable means to explore, in-situ, the Venusian atmosphere on a global scale. Flying over the ground at speeds exceeding 240 km/hour while floating in the Venusian skies near 55 km altitude for several weeks, such an aerostat can conduct a 'world tour' of our neighboring planet, as it circumnavigates the globe multiple times during its flight from equatorial to polar latitudes. Onboard science sensors can repeatedly and directly sample gas compositions, atmospheric pressures and temperatures and cloud particle properties, giving unprecedented insight into the chemical processes occurring within the sulfuric clouds. Additionally, interferometric tracking via Earth-based radio observatories can yield positions and windspeeds to better than 10 cm/sec over one-hour periods, providing important information for understanding the planet's meridional circulation and enigmatic zonal super-rotation, as well as local dynamics associated with meteorological processes. As well, hundreds of GCMS spectra collected during the flight can provide measurements of noble gas compositions and their isotopes with unprecedented accuracy, thereby enabling fundamental new insights into Venus's origin and evolution.

  5. Teaching and cultural education in the knowledge society. Evolutive analysis of a strategy of collaborative learning in Higher Education

    Directory of Open Access Journals (Sweden)

    Manuela FABBRI

    2011-12-01

    Full Text Available 0 0 1 214 1180 Instituto Universitario de Ciencias de la Educación 9 2 1392 14.0 Normal 0 21 false false false ES JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-ansi-language:ES; mso-fareast-language:EN-US;} This paper discuss in a pedagogical level an experience on the use of Forum as a telematic device. The part of e-learning comprised, together with contents and different kind of exercises, a forum. It was prepared for udergraduated students (third year in Social and Cultural Education (Faculty of Education, University of Bologna. From a brief analysis of the context for the Forum on collaborative learning, authors present a description of the quantitative data from experience, some reflections about the research for techno-social goals, and extract some conclusions from positive elements and limits when using TICs in Higher Education system. From assessment and analysis of the educational process and experience of social formation that develops in the Forum, the authors present an instructional design proposal from the critical and reflective paradigm, after evaluating various comments on the results, related with the strengths and limitations of the instrument in the university context. The conclusions guide the work in the subject of educational technology to not only a reflection of the disciplinary nature focused on the use of ICT, but also an approach to collaborative learning strategies and throughout lifelong learning

  6. Current challenges of Germany’s energy transition project and competing strategies of challengers and incumbents: The case of direct marketing of electricity from renewable energy sources

    International Nuclear Information System (INIS)

    Wassermann, Sandra; Reeg, Matthias; Nienhaus, Kristina

    2015-01-01

    Electricity generated by renewable energies (RES-E) already accounts for 25% of Germany’s electricity supply. This has led to recent discussions for a better market integration of RES-E. The paper examines how competing actors and their ideas on market integration developed new services for direct marketing according to their respective origins and tried to shape the regulatory framework. The paper analyses this process and explains the current shape of the field of direct marketing. Medium-sized structured actors, who favoured RES-E integration via the conventional wholesale power markets, and who formed early close coalitions with RES-E power producers at the same time, have been most successful in terms of market shares. Moreover, they have been very successful for different reasons in building-up coalitions with governance units and influencing the field rules and routines. Based on those findings, the paper will conclude with some policy advices for the future adjustment of the current regulative frameworks. As long as there is no evidence of how RES-E can be integrated most effectively and efficiently, policies should maintain a competition between different direct marketing strategies to find out which strategies serve the best in terms of achieving a successful energy transition. - Highlights: • Innovation sociological analysis of the market integration of electricity from renewables in the German electricity markets. • Direct marketing of RES-E seen as a new strategic action field in the German “Energiewende”. • Strategies of incumbent and challenger actors to shape the rules of the field. • Suggestions for the future design of policy instruments for direct marketing of RES-E

  7. Evolution of direct mechanisms with incident energy from the Coulomb-barrier to relativistic energies. - Two-center effects in nucleon transfer between nuclei. - Signatures of nucleon promotion in heavy ion reactions at barrier energies

    International Nuclear Information System (INIS)

    Oertzen, W. von; Voit, H.; Imanishi, B.

    1988-10-01

    This report contains a review article considering the evolution of direct mechanisms with incident energy in heavy ion reactions and two theoretical articles concerning two-center effects in transfer reactions between heavy ions and the nucleon promotion in heavy ion reactions. See hints under the relevant topics. (HSI)

  8. A Fly-Through Mission Strategy Targeting Peptide as a Signature of Chemical Evolution and Possible Life in Enceladus Plumes

    Science.gov (United States)

    Fujishima, Kosuke; Dziomba, Szymon; Takahagi, Wataru; Shibuya, Takazo; Takano, Yoshinori; Guerrouache, Mohamed; Carbonnier, Benjamin; Takai, Ken; Rothschild, Lynn J.; Yano, Hajime

    2016-01-01

    capillary electrophoresis (CE) under optimized conditions. We further conducted Enceladus plume fly-through capture experiment by accelerating peptides soaked in rock particles up to a speed of 5.7 km/s and capturing with originally developed hydrophobic silica aerogels. Direct peptide extraction with acetonitrile-water followed by CE analysis led to detection of only but two stereoisomeric acidic peptide peaks, presenting the first run-through hypervelocuty impact sample analysis targeting peptides as key molecule to to understand the ongoing astrobiology on Enceladus.

  9. Linking Contextual Factors with Rhetorical Pattern Shift: Direct and Indirect Strategies Recommended in English Business Communication Textbooks in China

    Science.gov (United States)

    Wang, Junhua; Zhu, Pinfan

    2011-01-01

    Scholars have consistently claimed that rhetorical patterns are culturally bound, and indirectness is a defining characteristic of Chinese writing. Through examining how the rhetorical mechanism of directness and indirectness is presented in 29 English business communication textbooks published in China, we explore how English business…

  10. Future Directions for Pain Management: Lessons from the Institute of Medicine Pain Report and the National Pain Strategy.

    Science.gov (United States)

    Mackey, Sean

    2016-02-01

    According to the Institute of Medicine Relieving Pain in America Report and the soon to be released National Pain Strategy, pain affects over 100 million Americans and costs our country in over $500 billion per year. We have a greater appreciation for the complex nature of pain and that it can develop into a disease in itself. As such, we need more efforts on prevention of chronic pain and for interdisciplinary approaches. For precision pain medicine to be successful, we need to link learning health systems with pain biomarkers (eg, genomics, proteomics, patient reported outcomes, brain markers) and its treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Under what conditions can a nonprescription drug label serve as refutation text? The role of directed attention and processing strategy

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2017-09-01

    Full Text Available Nonprescription drug labels are relatively ineffective in refuting drug misconceptions. We sought to improve the effectiveness of an aspirin label as a refutation text by manipulating selective attention and label-processing strategy. After reading a facsimile label, those of 196 undergraduates who attempted to explain why shaded drug facts are “easily confused” recalled more refuting drug facts than participants who attempted to explain why those facts are “easily ignored.” However, “easily confused” processing did not change truth ratings of misconceptions associated with those drug facts. We conclude that refuted misconceptions remain in memory but are inhibited by disconfirming drug facts.

  12. Influence of narrow fuel spray angle and split injection strategies on combustion efficiency and engine performance in a common rail direct injection diesel engine

    Directory of Open Access Journals (Sweden)

    Raouf Mobasheri

    2017-03-01

    Full Text Available Direct injection diesel engines have been widely used in transportation and stationary power systems because of their inherent high thermal efficiency. On the other hand, emission regulations such as NOx and particulates have become more stringent from the standpoint of preserving the environment in recent years. In this study, previous results of multiple injection strategies have been further investigated to analyze the effects of narrow fuel spray angle on optimum multiple injection schemes in a heavy duty common rail direct injection diesel engine. An advanced computational fluid dynamics simulation has been carried out on a Caterpillar 3401 diesel engine for a conventional part load condition in 1600 r/min at two exhaust gas recirculation rates. A good agreement of calculated and measured in-cylinder pressure, heat release rate and pollutant formation trends was obtained under various operating points. Three different included spray angles have been studied in comparison with the traditional spray injection angle. The results show that spray targeting is very effective for controlling the in-cylinder mixture distributions especially when it accompanied with various injection strategies. It was found that the optimum engine performance for simultaneous reduction of soot and NOx emissions was achieved with 105° included spray angle along with an optimized split injection strategy. The results show, in this case, the fuel spray impinges at the edge of the piston bowl and a counterclockwise flow motion is generated that pushes mixture toward the center of the piston bowl.

  13. Tailored central nervous system-directed treatment strategy for isolated CNS recurrence of adult acute myeloid leukemia.

    Science.gov (United States)

    Zheng, Changcheng; Liu, Xin; Zhu, Weibo; Cai, Xiaoyan; Wu, Jingsheng; Sun, Zimin

    2014-06-01

    The aim of this report was to investigate the tailored treatment strategies for isolated central nervous system (CNS) recurrence in adult patients with acute myeloid leukemia (AML). Isolated CNS recurrence was documented in 34 patients: there were 18, 6, and 10 patients with meningeal involvement type (type A), cranial nerve palsy type (type B), and myeloid sarcoma type (type C), respectively. For patients with type A, intrathecal chemotherapy was the predominant strategy. For type B, systemic HD-Ara-C with four cycles was the main treatment. For type C, cranial irradiation or craniospinal irradiation was adopted and two cycles of HD-Ara-C were given after the irradiation. The 5-year cumulative incidence of CNS recurrence was 12.8%. There was a significantly higher WBC count (32.6∼60.8 × 10(9)/l) in patients at first diagnosis who developed CNS recurrence (all of the three types) compared with patients with no CNS recurrence (10.1 × 10(9)/l) (P = 0.005). We found that a significantly more patients with AML-M5 and 11q23 abnormalities developed CNS recurrence in type A (P adult AML, but further studies are needed to improve the long-term survival.

  14. Microstructural evolution of direct chill cast Al-15.5Si-4Cu-1Mg-1Ni-0.5Cr alloy during solution treatment

    Directory of Open Access Journals (Sweden)

    He Kezhun

    2011-08-01

    Full Text Available Heat treatment has important influence on the microstructure and mechanical properties of Al-Si alloys. The most common used heat treatment method for these alloys is solution treatment followed by age-hardening. This paper investigates the microstructural evolution of a direct chill (DC cast Al-15.5Si-4Cu-1Mg-1Ni-0.5Cr alloy after solution treated at 500, 510, 520 and 530℃, respectively for different times. The major phases observed in the as-cast alloy are α-aluminum dendrite, primary Si particle, eutectic Si, Al7Cu4Ni, Al5Cu2Mg8Si6, Al15(Cr, Fe, Ni, Cu4Si2 and Al2Cu. The Al2Cu phase dissolves completely after being solution treated for 2 h at 500℃, while the eutectic Si, Al5Cu2Mg8Si6 and Al15(Cr, Fe, Ni, Cu4Si2 phases are insoluble. In addition, the Al7Cu4Ni phase is substituted by the Al3CuNi phase. The α-aluminum dendrite network disappears when the solution temperature is increased to 530℃. Incipient melting of the Al2Cu-rich eutectic mixture occurrs at 520℃, and melting of the Al5Cu2Mg8Si6 and Al3CuNi phases is observed at a solution temperature of 530℃. The void formation of the structure and deterioration of the mechanical properties are found in samples solution treated at 530℃.

  15. Multi-directional self-ion irradiation of thin gold films: A new strategy for achieving full texture control

    International Nuclear Information System (INIS)

    Seita, Matteo; Muff, Daniel; Spolenak, Ralph

    2011-01-01

    Highlights: → Multi-directional self-ion bombardment of Au films. → Extensive selective grain growth leads to single crystal-like films. → Texture rotation is prevented by the multi-directional irradiation process. → Texture rotation rate depends on the film initial defect density. - Abstract: Post-deposition ion bombardment can be employed to convert polycrystalline films into single crystals through a process of selective grain growth. Here we report a new technique that enables selective grain growth in self-ion bombarded gold films - a system in which the formation of large single crystal domains was prevented by the occurrence of ion-induced texture rotation. Our findings suggest that the extent of the texture rotation is a function of the ion fluence and the film initial microstructure.

  16. Direct in Situ Conversion of Metals into Metal-Organic Frameworks: A Strategy for the Rapid Growth of MOF Films on Metal Substrates.

    Science.gov (United States)

    Ji, Hoon; Hwang, Sunhyun; Kim, Keonmok; Kim, CheolGi; Jeong, Nak Cheon

    2016-11-30

    The fabrication of metal-organic framework (MOF) films on conducting substrates has demonstrated great potential in applications such as electronic conduction and sensing. For these applications, direct contact of the film to the conducting substrate without a self-assembled monolayer (SAM) is a desired step that must be achieved prior to the use of MOF films. In this report, we propose an in situ strategy for the rapid one-step conversion of Cu metal into HKUST-1 films on conducting Cu substrates. The Cu substrate acts both as a conducting substrate and a source of Cu 2+ ions during the synthesis of HKUST-1. This synthesis is possible because of the simultaneous reaction of an oxidizing agent and a deprotonating agent, in which the former agent dissolves the metal substrate to form Cu 2+ ions while the latter agent deprotonates the ligand. Using this strategy, the HKUST-1 film could not only be rapidly synthesized within 5 min but also be directly attached to the Cu substrate. Based on microscopic studies, we propose a plausible mechanism for the growth reaction. Furthermore, we show the versatility of this in situ conversion methodology, applying it to ZIF-8, which comprises Zn 2+ ions and imidazole-based ligands. Using an I 2 -filled HKUST-1 film, we further demonstrate that the direct contact of the MOF film to the conducting substrate makes the material more suitable for use as a sensor or electronic conductor.

  17. Decentralized energy management strategy based on predictive controllers for a medium voltage direct current photovoltaic electric vehicle charging station

    International Nuclear Information System (INIS)

    Torreglosa, Juan P.; García-Triviño, Pablo; Fernández-Ramirez, Luis M.; Jurado, Francisco

    2016-01-01

    Highlights: • Electric vehicle charging station supplied by photovoltaic, batteries and grid connection is analyzed. • The bus voltage is the key parameter for controlling the system by decentralized approach. • Decentralized control approach facilities the enlargement of the system. • Photovoltaic and battery systems are controlled by model predictive controllers. • Response by model predictive controllers improves that by PI controllers. - Abstract: The use of distributed charging stations based on renewable energy sources for electric vehicles has increased in recent years. Combining photovoltaic solar energy and batteries as energy storage system, directly tied into a medium voltage direct current bus, and with the grid support, results to be an interesting option for improving the operation and efficiency of electric vehicle charging stations. In this paper, an electric vehicle charging station supplied by photovoltaic solar panels, batteries and with grid connection is analysed and evaluated. A decentralized energy management system is developed for regulating the energy flow among the photovoltaic system, the battery and the grid in order to achieve the efficient charging of electric vehicles. The medium voltage direct current bus voltage is the key parameter for controlling the system. The battery is controlled by a model predictive controller in order to keep the bus voltage at its reference value. Depending on the state-of-charge of the battery and the bus voltage, the photovoltaic system can work at maximum power point tracking mode or at bus voltage sustaining mode, or even the grid support can be needed. The results demonstrate the proper operation and energy management of the electric vehicle charging station under study.

  18. Evolution strategies for robust optimization

    NARCIS (Netherlands)

    Kruisselbrink, Johannes Willem

    2012-01-01

    Real-world (black-box) optimization problems often involve various types of uncertainties and noise emerging in different parts of the optimization problem. When this is not accounted for, optimization may fail or may yield solutions that are optimal in the classical strict notion of optimality, but

  19. Effects of turbulence enhancement on combustion process using a double injection strategy in direct-injection spark-ignition (DISI) gasoline engines

    International Nuclear Information System (INIS)

    Kim, Taehoon; Song, Jingeun; Park, Sungwook

    2015-01-01

    Highlights: • Using double injection strategy, turbulent kinetic energy can be improved with slight decrease in mixture homogeneity. • Retarded first injection timing reduces vapor fuel loss to intake port. • Double injection increases tumble intensity. • High turbulent intensity caused by double injection increases flame propagation speed. - Abstract: Direct-i