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Sample records for directed evolution approaches

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

    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 ...

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

    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.

  3. Novel Random Mutagenesis Method for Directed Evolution.

    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.

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

    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....

  5. Directed evolution of enzymes using microfluidic chips

    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.

  6. Evolution of genetic architecture under directional selection.

    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.

  7. Student Teachers' Approaches to Teaching Biological Evolution

    Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

    2015-06-01

    Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution teaching can be particularly challenging for student teachers who are just beginning to gain pedagogical knowledge and pedagogical content knowledge related to evolution teaching and who seek approval from university supervisors and cooperating teachers. Science teacher educators need to know how to best support student teachers as they broach the sometimes daunting task of teaching evolution within student teaching placements. This multiple case study report documents how three student teachers approached evolution instruction and what influenced their approaches. Data sources included student teacher interviews, field note observations for 4-5 days of evolution instruction, and evolution instructional artifacts. Data were analyzed using grounded theory approaches to develop individual cases and a cross-case analysis. Seven influences (state exams and standards, cooperating teacher, ideas about teaching and learning, concerns about evolution controversy, personal commitment to evolution, knowledge and preparation for teaching evolution, and own evolution learning experiences) were identified and compared across cases. Implications for science teacher preparation and future research are provided.

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

    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

  9. A stochastic approach to chemical evolution

    Copi, C.J.

    1997-01-01

    Observations of elemental abundances in the Galaxy have repeatedly shown an intrinsic scatter as a function of time and metallicity. The standard approach to chemical evolution does not attempt to address this scatter in abundances since only the mean evolution is followed. In this work, the scatter is addressed via a stochastic approach to solving chemical evolution models. Three simple chemical evolution scenarios are studied using this stochastic approach: a closed box model, an infall model, and an outflow model. These models are solved for the solar neighborhood in a Monte Carlo fashion. The evolutionary history of one particular region is determined randomly based on the star formation rate and the initial mass function. Following the evolution in an ensemble of such regions leads to the predicted spread in abundances expected, based solely on different evolutionary histories of otherwise identical regions. In this work, 13 isotopes are followed, including the light elements, the CNO elements, a few α-elements, and iron. It is found that the predicted spread in abundances for a 10 5 M circle-dot region is in good agreement with observations for the α-elements. For CN, the agreement is not as good, perhaps indicating the need for more physics input for low-mass stellar evolution. Similarly for the light elements, the predicted scatter is quite small, which is in contradiction to the observations of 3 He in HII regions. The models are tuned for the solar neighborhood so that good agreement with HII regions is not expected. This has important implications for low-mass stellar evolution and on using chemical evolution to determine the primordial light-element abundances in order to test big bang nucleosynthesis. copyright 1997 The American Astronomical Society

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

    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.

  11. Evolution of the mirror approach to fusion: some conjectures

    Post, R.E.

    1984-01-01

    Some possible directions for the future evolution of the mirror approach to fusion are outlined, in the context of economically-motivated criteria. Speculations are given as to the potential advantages, economic and otherwise, of the use of axially-symmetric systems, operated in semi-collisional regimes of lower Q (fusion power balance ratio) than that projected for present-day tandem mirror designs. These regims include barely tandem modes, and ion-heated modes, in association with higher efficiency direct conversion. Another possible economically advantageous approach mentioned is the use of a tandem mirror plasma to stabilize a FRM (field-reversed mirror) plasma, with potential synergistic advantages

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

    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...

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

    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…

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

    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

  15. The Evolution of the Direct Marketing Industry in Italy

    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.

  16. Directed Evolution of Membrane Transport Using Synthetic Selections

    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...

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

    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.

  18. Student Teachers' Approaches to Teaching Biological Evolution

    Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

    2015-01-01

    Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution…

  19. Evolution, Physics, and Cancer: Disrupting Traditional Approache

    Austin, Robert

    Physicists who were recruited to try and assist with the stubbornly constant mortality rates of cancer world-wide over the past 100 years have basically had the invitation withdrawn by the oncology community. The oncologists became annoyed with the independence of thought and the skepticism of some physicists with continuation of the present paradigm of the cancer genome as the rosette stone as the key to cancer. To quote a recent letter in Physics Today: ``Curing cancer is a complex biological problem to be solved by biologists''. Apparently our mission as minions is is to be high-level technicians. But I think that is wrong and will lead to continuation of the string of failures and deceptions foisted on the public at large by the Medical Industrial Complex, I think we really need to re-think cancer as a phenomena which is driven by evolution and may be desired by the organism and be a product of both the aging of the proteome and the genome. Further, searching for mutations (The Cancer Genome) may be completely the wrong direction, searching for protected genes may be as important as looking for mutated genes. I'll try to present the case that physicists should not have been kicked out of the Medical Industrial Complex that keeps the cancer business humming and profitable.

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

    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.

  1. Selection platforms for directed evolution in synthetic biology.

    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).

  2. A Constructive Approach To Software Evolution

    Ciraci, S.; van den Broek, P.M.; Aksit, Mehmet

    2007-01-01

    In many software design and evaluation techniques, either the software evolution problem is not systematically elaborated, or only the impact of evolution is considered. Thus, most of the time software is changed by editing the components of the software system, i.e. breaking down the software

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

    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.

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

    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.

  5. Directed evolution of an extremely stable fluorescent protein.

    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.

  6. Laughter as an approach to vocal evolution: The bipedal theory.

    Provine, Robert R

    2017-02-01

    Laughter is a simple, stereotyped, innate, human play vocalization that is ideal for the study of vocal evolution. The basic approach of describing the act of laughter and when we do it has revealed a variety of phenomena of social, linguistic, and neurological significance. Findings include the acoustic structure of laughter, the minimal voluntary control of laughter, the punctuation effect (which describes the placement of laughter in conversation and indicates the dominance of speech over laughter), and the role of laughter in human matching and mating. Especially notable is the use of laughter to discover why humans can speak and other apes cannot. Quadrupeds, including our primate ancestors, have a 1:1 relation between breathing and stride because their thorax must absorb forelimb impacts during running. The direct link between breathing and locomotion limits vocalizations to short, simple utterances, such as the characteristic panting chimpanzee laugh (one sound per inward or outward breath). The evolution of bipedal locomotion freed the respiration system of its support function during running, permitting greater breath control and the selection for human-type laughter (a parsed exhalation), and subsequently the virtuosic, sustained, expiratory vocalization of speech. This is the basis of the bipedal theory of speech evolution.

  7. TRENDS IN THE EVOLUTION OF WORLDWIDE FOREIGN DIRECT INVESTMENTS

    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.

  8. A cultural evolution approach to digital media

    Acerbi, A.

    2016-01-01

    Digital media have today an enormous diffusion, and their influence on the behaviour of a vast part of the human population can hardly be underestimated. In this review I propose that cultural evolution theory, including both a sophisticated view of human behaviour and a methodological attitude to

  9. Sociohistorical evolution of judo: introductory approaches

    Orozimbo Cordeiro Júnior

    2008-06-01

    Full Text Available The sociohistorical evolution of judo provided by the research project Methodology for teaching judo from the critical–excelling stance is discussed in this article. The aim of the project was to establish a plan for systematizing judo as body culture constituent and scholastic knowledge of physical education. The ancillary pedagogical material is constituted by an introduction, objectives, contents, teaching methodology and evaluation system.

  10. Directed evolution of a thermostable l-aminoacylase biocatalyst

    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. A Cultural Evolution Approach to Digital Media.

    Acerbi, Alberto

    2016-01-01

    Digital media have today an enormous diffusion, and their influence on the behavior of a vast part of the human population can hardly be underestimated. In this review I propose that cultural evolution theory, including both a sophisticated view of human behavior and a methodological attitude to modeling and quantitative analysis, provides a useful framework to study the effects and the developments of media in the digital age. I will first give a general presentation of the cultural evolution framework, and I will then introduce this more specific research program with two illustrative topics. The first topic concerns how cultural transmission biases, that is, simple heuristics such as "copy prestigious individuals" or "copy the majority," operate in the novel context of digital media. The existence of transmission biases is generally justified with their adaptivity in small-scale societies. How do they operate in an environment where, for example, prestigious individuals possess not-relevant skills, or popularity is explicitly quantified and advertised? The second aspect relates to fidelity of cultural transmission. Digitally-mediated interactions support cheap and immediate high-fidelity transmission, in opposition, for example, to oral traditions. How does this change the content that is more likely to spread? Overall, I suggest the usefulness of a "long view" to our contemporary digital environment, contextualized in cognitive science and cultural evolution theory, and I discuss how this perspective could help us to understand what is genuinely new and what is not.

  12. A cultural evolution approach to digital media

    Alberto Acerbi

    2016-12-01

    Full Text Available Digital media have today an enormous diffusion, and their influence on the behaviour of a vast part of the human population can hardly be underestimated. In this review I propose that cultural evolution theory, including both a sophisticated view of human behaviour and a methodological attitude to modelling and quantitative analysis, provides a useful framework to study the effects and the developments of media in the digital age. I will first give a general presentation of the cultural evolution framework, and I will then introduce this more specific research program with two illustrative topics.The first topic concerns how cultural transmission biases, that is, simple heuristics such as copy prestigious individuals or copy the majority, operate in the novel context of digital media. The existence of transmission biases is generally justified with their adaptivity in small-scale societies. How do they operate in an environment where, for example, prestigious individuals possess not-relevant skills, or popularity is explicitly quantified and advertised?The second aspect relates to fidelity of cultural transmission. Digitally-mediated interactions support cheap and immediate high-fidelity transmission, in opposition, for example, to oral traditions. How does this change the content that is more likely to spread? Overall, I suggest the usefulness of a long view to our contemporary digital environment, contextualised in cognitive science and cultural evolution theory, and I discuss how this perspective could help us to understand what is genuinely new and what is not.

  13. A Cultural Evolution Approach to Digital Media

    Acerbi, Alberto

    2016-01-01

    Digital media have today an enormous diffusion, and their influence on the behavior of a vast part of the human population can hardly be underestimated. In this review I propose that cultural evolution theory, including both a sophisticated view of human behavior and a methodological attitude to modeling and quantitative analysis, provides a useful framework to study the effects and the developments of media in the digital age. I will first give a general presentation of the cultural evolution framework, and I will then introduce this more specific research program with two illustrative topics. The first topic concerns how cultural transmission biases, that is, simple heuristics such as “copy prestigious individuals” or “copy the majority,” operate in the novel context of digital media. The existence of transmission biases is generally justified with their adaptivity in small-scale societies. How do they operate in an environment where, for example, prestigious individuals possess not-relevant skills, or popularity is explicitly quantified and advertised? The second aspect relates to fidelity of cultural transmission. Digitally-mediated interactions support cheap and immediate high-fidelity transmission, in opposition, for example, to oral traditions. How does this change the content that is more likely to spread? Overall, I suggest the usefulness of a “long view” to our contemporary digital environment, contextualized in cognitive science and cultural evolution theory, and I discuss how this perspective could help us to understand what is genuinely new and what is not. PMID:28018200

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

    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.

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

    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.

  16. Thermal force approach to molecular evolution.

    Braun, Dieter; Libchaber, Albert

    2004-06-01

    Recent experiments are discussed where temperature gradients across mesoscopic pores are shown to provide essential mechanisms for autonomous molecular evolution. On the one hand, laminar thermal convection can drive DNA replication as the molecules are continuously cycled between hot and cold regions of a chamber. On the other hand, thermophoresis can accumulate charged biopolymers in similar convection settings. The experiments show that temperature differences analogous to those across porous rocks present a robust nonequilibrium boundary condition to feed the replication and accumulation of evolving molecules. It is speculated that similar nonequilibrium conditions near porous submarine hydrothermal mounds could have triggered the origin of life. In such a scenario, the encapsulation of cells with membranes would be a later development. It is expected that detailed studies of mesoscopic boundary conditions under nonequilibrium conditions will reveal new connecting pieces in the fascinating puzzle of the origins of life.

  17. Perturbative evolution: a different approach at small x

    Donnachie, A. [University of Manchester, School of Physics and Astromony, Manchester (United Kingdom); Landshoff, P.V. [DAMTP, Cambridge University, Cambridge (United Kingdom)

    2017-08-15

    We propose an approach to DGLAP evolution at small x that circumvents the usual problem that a perturbation expansion is not valid there. The data for the charm structure function are important to motivate the method, and it describes them much more successfully than the conventional approach. (orig.)

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

    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.

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

    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

  20. Directed Evolution and Structural Characterization of a Simvastatin Synthase

    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.

  1. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution

    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

  2. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.

    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.

  3. ESDIS DOI System, Approach, and Future Direction

    Wanchoo, L.; James, N.

    2013-12-01

    NASA's Earth Science Data and Information System (ESDIS) Project began investigating the use of Digital Object Identifiers (DOIs) in 2010 with the goal of assigning DOIs to various data products. These data products are archived and distributed by various Distributed Active Archive Centers (DAACs) located across the United States. Each data center has a unique approach and process for generating and archiving a variety of data products that are used for global change research. These varied approaches present a challenge for developing a DOI solution that fits all the possible variations. To address this challenge, ESDIS developed processes, guidelines, and several models for creating and assigning DOIs. Initially the system was started as a prototype approach and now it is fully operational. In February 2012, ESDIS joined the California Digital Library (CDL) EZID for registering the EOSDIS-related DOIs. ESDIS's DOI operational process allows for reserving DOIs while data providers are finalizing the DOIs and its associated elements. This flexibility allows data providers to embed and test the DOI in the data product metadata before formally registering with EZID. Data providers can change any DOI metadata, including the DOI name as long as it has not been registered or reserved by another data provider. ESDIS assures the uniqueness of the DOI names before it is registered. Currently, ESDIS has 146 data product DOIs registered with EZID and data providers have reserved an additional 93 DOIs with ESDIS. A semi-automated approach is being developed for processing and validating the DOI information provided by the data providers and will cover all the steps from the collection to the registration of DOIs. ESDIS's DOI concept utilizes a few mandatory metadata elements that effectively identify the data products and the source of availability. Of these elements, the Uniform Resource Locator (URL) attribute has the very important function of identifying the landing page

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

    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.

  5. Global evolution: New approach to understanding

    Damiani, V.

    1993-01-01

    Current threats to the health of the environment - urban air pollution, deforestation, water pollution, etc. are taking on an ever increasing global dimension and it is becoming clear that it will be impossible to develop real solutions to these problems without effectively and contemporaneously resolving the deep social and political problems which are affecting just about every part of the globe. The cause of past failures in environmental protection policy implementation can be ascribed to one of the main defects of our society - that of not having cultivated intuitive knowledge through direct as opposed to intellectual experience; and this defect was probably the result of man having separated biological and cultural aspects from human nature during the course of civilization. To accomplish the formidable task of global environmental restoration, mankind must re-program his ways of living and reasoning which are not in harmony with nature. Conventional rational methods of thinking, which are highly linear, must give way to an intuitive process of comprehension to allow man to successfully deal with the maintenance of the earth's dynamic and non-linear ecosystems and socio-economic frameworks

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

    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. A structuralist approach in the study of evolution and classification

    Hammen, van der L.

    1985-01-01

    A survey is given of structuralism as a method that can be applied in the study of evolution and classification. The results of a structuralist approach are illustrated by examples from the laws underlying numerical changes, from the laws underlying changes in the chelicerate life-cycle, and from

  8. An ensemble approach to the evolution of complex systems

    2014-03-15

    Mar 15, 2014 ... [Arpağ G and Erzan A 2014 An ensemble approach to the evolution of complex systems. J. Biosci. ... almost nothing about all the different ways in which your ...... energy cost to the organism of the maintenance, replication,.

  9. SEAS: A simulated evolution approach for analog circuit synthesis

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Mouthaan, A.J.; Wallinga, Hans

    1991-01-01

    The authors present a simulated evolution approach for analog circuit synthesis based on an analogy with the natural selection process in biological environments and on the iterative improvements in solving engineering problems. A prototype framework based on this idea, called SEAS, has been

  10. Spatial Economics: The Evolution of Approaches and Methodology

    Minakir P. A.

    2010-06-01

    Full Text Available The evolution of theoretical principles and approaches to the study of spatial organization of the economy is set forth. The changes in the content of the category «economic region» are analyzed. A comparative assessment is given of theoretical approaches to studying spatial aspects of the economy. The limited character of theoretical and applied regional economic tools in studying spatial organization and spatial interactions between economic agents of the modern economy is shown

  11. Two-component multistep direct reactions: A microscopic approach

    Koning, A.J.; Chadwick, M.B.

    1998-03-01

    The authors present two principal advances in multistep direct theory: (1) A two-component formulation of multistep direct reactions, where neutron and proton excitations are explicitly accounted for in the evolution of the reaction, for all orders of scattering. While this may at first seem to be a formidable task, especially for multistep processes where the many possible reaction pathways becomes large in a two-component formalism, the authors show that this is not so -- a rather simple generalization of the FKK convolution expression 1 automatically generates these pathways. Such considerations are particularly relevant when simultaneously analyzing both neutron and proton emission spectra, which is always important since these processes represent competing decay channels. (2) A new, and fully microscopic, method for calculating MSD cross sections which does not make use of particle-hole state densities but instead directly calculates cross sections for all possible particle-hole excitations (again including an exact book-keeping of the neutron/proton type of the particle and hole at all stages of the reaction) determined from a simple non-interacting shell model. This is in contrast to all previous numerical approaches which sample only a small number of such states to estimate the DWBA strength, and utilize simple analytical formulae for the partial state density, based on the equidistant spacing model. The new approach has been applied, along with theories for multistep compound, compound, and collective reactions, to analyze experimental emission spectra for a range of targets and energies. The authors show that the theory correctly accounts for double-differential nucleon spectra

  12. Teaching Higher Order Thinking in the Introductory MIS Course: A Model-Directed Approach

    Wang, Shouhong; Wang, Hai

    2011-01-01

    One vision of education evolution is to change the modes of thinking of students. Critical thinking, design thinking, and system thinking are higher order thinking paradigms that are specifically pertinent to business education. A model-directed approach to teaching and learning higher order thinking is proposed. An example of application of the…

  13. Structural Approaches to Sequence Evolution Molecules, Networks, Populations

    Bastolla, Ugo; Roman, H. Eduardo; Vendruscolo, Michele

    2007-01-01

    Structural requirements constrain the evolution of biological entities at all levels, from macromolecules to their networks, right up to populations of biological organisms. Classical models of molecular evolution, however, are focused at the level of the symbols - the biological sequence - rather than that of their resulting structure. Now recent advances in understanding the thermodynamics of macromolecules, the topological properties of gene networks, the organization and mutation capabilities of genomes, and the structure of populations make it possible to incorporate these key elements into a broader and deeply interdisciplinary view of molecular evolution. This book gives an account of such a new approach, through clear tutorial contributions by leading scientists specializing in the different fields involved.

  14. Middlemen: A Directed Search Equilibrium Approach

    Makoto Watanabe

    2012-01-01

    This paper studies an intermediated market operated by middlemen with high inventory holdings. I present a directed search model in which middlemen are less likely to experience a stockout because they have the advantage of inventory capacity, relative to other sellers. The model explains why popular items are sold at a larger premium, and everyday items at a larger discount, by large-scaled intermediaries. The concentration of middlemen's market, i.e., few middlemen, each with large capacity...

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

    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.

  16. Numerical approaches to time evolution of complex quantum systems

    Fehske, Holger; Schleede, Jens; Schubert, Gerald; Wellein, Gerhard; Filinov, Vladimir S.; Bishop, Alan R.

    2009-01-01

    We examine several numerical techniques for the calculation of the dynamics of quantum systems. In particular, we single out an iterative method which is based on expanding the time evolution operator into a finite series of Chebyshev polynomials. The Chebyshev approach benefits from two advantages over the standard time-integration Crank-Nicholson scheme: speedup and efficiency. Potential competitors are semiclassical methods such as the Wigner-Moyal or quantum tomographic approaches. We outline the basic concepts of these techniques and benchmark their performance against the Chebyshev approach by monitoring the time evolution of a Gaussian wave packet in restricted one-dimensional (1D) geometries. Thereby the focus is on tunnelling processes and the motion in anharmonic potentials. Finally we apply the prominent Chebyshev technique to two highly non-trivial problems of current interest: (i) the injection of a particle in a disordered 2D graphene nanoribbon and (ii) the spatiotemporal evolution of polaron states in finite quantum systems. Here, depending on the disorder/electron-phonon coupling strength and the device dimensions, we observe transmission or localisation of the matter wave.

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

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

    2016-01-01

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

  18. Elastic Multibody Dynamics A Direct Ritz Approach

    Bremer, H

    2008-01-01

    This textbook is an introduction to and exploration of a number of core topics in the field of applied mechanics: On the basis of Lagrange's Principle, a Central Equation of Dynamics is presented which yields a unified view on existing methods. From these, the Projection Equation is selected for the derivation of the motion equations of holonomic and of non-holonomic systems. The method is applied to rigid multibody systems where the rigid body is defined such that, by relaxation of the rigidity constraints, one can directly proceed to elastic bodies. A decomposition into subsystems leads to a minimal representation and to a recursive representation, respectively, of the equations of motion. Applied to elastic multibody systems one obtains, along with the use of spatial operators, a straight-on procedure for the interconnected partial and ordinary differential equations and the corresponding boundary conditions. The spatial operators are eventually applied to a RITZ series for approximation. The resulting equ...

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

    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...

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

    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.

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

    2013-12-01

    Dec 1, 2013 ... 1School of Mathematics and Applied Statistics, University of Wollongong, Wollongong,. NSW 2522 ... the nonlinear phenomena as well as their further applications in the real-life situations, it is ... concentration gradient. Thus ...

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

    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. The evolution of physician-directed managed care.

    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.

  4. Computational design of chimeric protein libraries for directed evolution.

    Silberg, Jonathan J; Nguyen, Peter Q; Stevenson, Taylor

    2010-01-01

    The best approach for creating libraries of functional proteins with large numbers of nondisruptive amino acid substitutions is protein recombination, in which structurally related polypeptides are swapped among homologous proteins. Unfortunately, as more distantly related proteins are recombined, the fraction of variants having a disrupted structure increases. One way to enrich the fraction of folded and potentially interesting chimeras in these libraries is to use computational algorithms to anticipate which structural elements can be swapped without disturbing the integrity of a protein's structure. Herein, we describe how the algorithm Schema uses the sequences and structures of the parent proteins recombined to predict the structural disruption of chimeras, and we outline how dynamic programming can be used to find libraries with a range of amino acid substitution levels that are enriched in variants with low Schema disruption.

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

    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.

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

    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...

  7. 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

    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.

  8. EXTENDE MODEL OF COMPETITIVITY THROUG APPLICATION OF NEW APPROACH DIRECTIVES

    Slavko Arsovski

    2009-03-01

    Full Text Available The basic subject of this work is the model of new approach impact on quality and safety products, and competency of our companies. This work represents real hypothesis on the basis of expert's experiences, in regard to that the infrastructure with using new approach directives wasn't examined until now, it isn't known which product or industry of Serbia is related to directives of the new approach and CE mark, and it is not known which are effects of the use of the CE mark. This work should indicate existing quality reserves and product's safety, the level of possible competency improvement and increasing the profit by discharging new approach directive requires.

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

    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)

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

    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.

  11. The evolution of green jobs in Scotland: A hybrid approach

    Connolly, Kevin; Allan, Grant J; McIntyre, Stuart G

    2016-01-01

    In support of its ambitious target to reduce CO_2 emissions the Scottish Government is aiming to have the equivalent of 100% of Scottish electricity consumption generated from renewable sources by 2020. This is, at least in part, motivated by an expectation of subsequent employment growth in low carbon and renewable energy technologies; however there is no official data source to track employment in these areas. This has led to a variety of definitions, methodologies and alternative estimates being produced. Building on a recent study (Bishop and Brand, 2013) we develop a “hybrid” approach which combines the detail of “bottom-up” surveys with “top-down” trend data to produce estimates on employment in Low Carbon Environmental Goods and Services (LCEGS). We demonstrate this methodology to produce estimates for such employment in Scotland between 2004 and 2012. Our approach shows how survey and official sources can combine to produce a more timely measure of employment in LCEGS activities, assisting policymakers in tracking, consistently, developments. Applying our approach, we find that over this period employment in LCEGS in Scotland grew, but that this was more volatile than aggregate employment, and in particular that employment in this sector was particularly badly hit during the great recession. - Highlights: • A “hybrid” approach estimates green jobs from bottom-up detail and top-down data. • Illustrative results show the evolution of such jobs in Scotland from 2004 to 2012. • Method provides policymakers a timely measure of the jobs success of energy policy.

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

    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.

  13. A quantitative approach to evolution of music and philosophy

    Vieira, Vilson; Fabbri, Renato; Travieso, Gonzalo; Oliveira Jr, Osvaldo N; Costa, Luciano da Fontoura

    2012-01-01

    The development of new statistical and computational methods is increasingly making it possible to bridge the gap between hard sciences and humanities. In this study, we propose an approach based on a quantitative evaluation of attributes of objects in fields of humanities, from which concepts such as dialectics and opposition are formally defined mathematically. As case studies, we analyzed the temporal evolution of classical music and philosophy by obtaining data for 8 features characterizing the corresponding fields for 7 well-known composers and philosophers, which were treated with multivariate statistics and pattern recognition methods. A bootstrap method was applied to avoid statistical bias caused by the small sample data set, with which hundreds of artificial composers and philosophers were generated, influenced by the 7 names originally chosen. Upon defining indices for opposition, skewness and counter-dialectics, we confirmed the intuitive analysis of historians in that classical music evolved according to a master–apprentice tradition, while in philosophy changes were driven by opposition. Though these case studies were meant only to show the possibility of treating phenomena in humanities quantitatively, including a quantitative measure of concepts such as dialectics and opposition, the results are encouraging for further application of the approach presented here to many other areas, since it is entirely generic. (paper)

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

    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.

  15. Foreign Direct Investment versus Portfolio Investment : A Global Games Approach

    Yamin Ahmad; Pietro Cova; Rodrigo Harrison

    2004-01-01

    We present a model of investment under uncertainty about fundamentals, using a global games approach. Goldstein & Razin (2003) show that there is an information based trade-off between foreign direct investment (FDI) and portfolio investment (PI) which rationalizes some well known stylised facts in the literature - the relative volatility and reversibility of foreign direct investment versus portfolio investment. We extend their result and show that uncertainty about fundamentals does not imp...

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

    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

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

    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,...

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

    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...

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

    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...

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

    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

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

    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.

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

    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.

  3. An evolution of image source camera attribution approaches.

    Jahanirad, Mehdi; Wahab, Ainuddin Wahid Abdul; Anuar, Nor Badrul

    2016-05-01

    researchers, are also critically analysed and further categorised into four different classes, namely, optical aberrations based, sensor camera fingerprints based, processing statistics based and processing regularities based, to present a classification. Furthermore, this paper aims to investigate the challenging problems, and the proposed strategies of such schemes based on the suggested taxonomy to plot an evolution of the source camera attribution approaches with respect to the subjective optimisation criteria over the last decade. The optimisation criteria were determined based on the strategies proposed to increase the detection accuracy, robustness and computational efficiency of source camera brand, model or device attribution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. VATS Lobectomy: Surgical Evolution from Conventional VATS to Uniportal Approach

    Diego Gonzalez-Rivas

    2012-01-01

    Full Text Available There is no standardized technique for the VATS lobectomy, though most centres use 2 ports and add a utility incision. However, the procedure can be performed by eliminating the two small ports and using only the utility incision with similar outcomes. Since 2010, when the uniportal approach was introduced for major pulmonary resection, the technique has been spreading worldwide. The single-port technique provides a direct view to the target tissue. The conventional triple port triangulation creates a new optical plane with genesis of dihedral or torsional angle that is not favorable with standard two-dimension monitors. The parallel instrumentation achieved during single-port approach mimics inside the maneuvers performed during open surgery. Furthermore, it represents the less invasive approach possible, and avoiding the use of trocar, we minimize the compression of the intercostal nerve. Further development of new technologies like sealing devices for all vessels and fissure, robotic arms that open inside the thorax, and wireless cameras will facilitate the uniportal approach to become the standard surgical procedure for pulmonary resection in most thoracic departments.

  5. Horizontal Directional Drilling (HDD) for shore approach applications

    Smith, Neil [MGI do Brasil Ltda., Rio de Janeiro, RJ (Brazil)

    2003-07-01

    Horizontal directional drilling (HDD) has become a commonly used construction method for pipeline shore approaches. HDD can mitigate environmental impact, provide greater burial depths and minimize construction schedules. The risks that are associated with HDD river crossings, which are generally well recognized, also apply to HDD shore approaches where they are combined with specific risks occurring from working in the marine environment. The shore approach projects of The Bronx and Hunts Point provide good practical examples of the benefits of this technology in spite of the various challenges encountered. (author)

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

    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.

  7. Intelligent Resource Management for Local Area Networks: Approach and Evolution

    Meike, Roger

    1988-01-01

    The Data Management System network is a complex and important part of manned space platforms. Its efficient operation is vital to crew, subsystems and experiments. AI is being considered to aid in the initial design of the network and to augment the management of its operation. The Intelligent Resource Management for Local Area Networks (IRMA-LAN) project is concerned with the application of AI techniques to network configuration and management. A network simulation was constructed employing real time process scheduling for realistic loads, and utilizing the IEEE 802.4 token passing scheme. This simulation is an integral part of the construction of the IRMA-LAN system. From it, a causal model is being constructed for use in prediction and deep reasoning about the system configuration. An AI network design advisor is being added to help in the design of an efficient network. The AI portion of the system is planned to evolve into a dynamic network management aid. The approach, the integrated simulation, project evolution, and some initial results are described.

  8. Stochastic Loewner evolution as an approach to conformal field theory

    Mueller-Lohmann, Annekathrin

    2008-01-01

    The main focus on this work lies on the relationship between two-dimensional boundary Conformal Field Theories (BCFTs) and SCHRAMM-LOEWNER Evolutions (SLEs) as motivated by their connection to the scaling limit of Statistical Physics models at criticality. The BCFT approach used for the past 25 years is based on the algebraic formulation of local objects such as fields and their correlations in these models. Introduced in 1999, SLE describes the physical properties from a probabilistic point of view, studying measures on growing curves, i.e. global objects such as cluster interfaces. After a short motivation of the topic, followed by a more detailed introduction to two-dimensional boundary Conformal Field Theory and SCHRAMM-LOEWNER Evolution, we present the results of our original work. We extend the method of obtaining SLE variants for a change of measure of the single SLE to derive the most general BCFT model that can be related to SLE. Moreover, we interpret the change of the measure in the context of physics and Probability Theory. In addition, we discuss the meaning of bulk fields in BCFT as bulk force-points for the SLE variant SLE (κ, vector ρ). Furthermore, we investigate the short-distance expansion of the boundary condition changing fields, creating cluster interfaces that can be described by SLE, with other boundary or bulk fields. Thereby we derive new SLE martingales related to the existence of boundary fields with vanishing descendant on level three. We motivate that the short-distance scaling law of these martingales as adjustment of the measure can be interpreted as the SLE probability of curves coming close to the location of the second field. Finally, we extend the algebraic κ-relation for the allowed variances in multiple SLE, arising due to the commutation requirement of the infinitesimal growth operators, to the joint growth of two SLE traces. The analysis straightforwardly suggests the form of the infinitesimal LOEWNER mapping of joint

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

    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. Constructive Approaches for Understanding the Origin of Self-Replication and Evolution

    Norikazu Ichihashi

    2016-07-01

    Full Text Available The mystery of the origin of life can be divided into two parts. The first part is the origin of biomolecules: under what physicochemical conditions did biomolecules such as amino acids, nucleotides, and their polymers arise? The second part of the mystery is the origin of life-specific functions such as the replication of genetic information, the reproduction of cellular structures, metabolism, and evolution. These functions require the coordination of many different kinds of biological molecules. A direct strategy to approach the second part of the mystery is the constructive approach, in which life-specific functions are recreated in a test tube from specific biological molecules. Using this approach, we are able to employ design principles to reproduce life-specific functions, and the knowledge gained through the reproduction process provides clues as to their origins. In this mini-review, we introduce recent insights gained using this approach, and propose important future directions for advancing our understanding of the origins of life.

  11. Direct and semi-direct approaches to lepton mixing with a massless neutrino

    King, Stephen F.; Ludl, Patrick Otto

    2016-01-01

    We discuss the possibility of enforcing a massless Majorana neutrino in the direct and semi-direct approaches to lepton mixing, in which the PMNS matrix is partly predicted by subgroups of a discrete family symmetry, extending previous group searches up to order 1535. We find a phenomenologically viable scheme for the semi-direct approach based on Q(648) which contains Δ(27) and the quaternion group as subgroups. This leads to novel predictions for the first column of the PMNS matrix corresponding to a normal neutrino mass hierarchy with m_1=0, and sum rules for the mixing angles and phase which are characterised by the solar angle being on the low side θ_1_2∼31"∘ and the Dirac (oscillation) CP phase δ being either about ±45"∘ or ±π.

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

    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. Textural Evolution During Micro Direct Metal Deposition of NiTi Alloy

    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.

  14. Evolution of approaches to viral safety issues for biological products.

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

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

    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...

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

    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

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

    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.

  18. Approach to interior design for passive direct gain solar homes

    Kachadorian, C.C.

    1980-01-01

    In response to requests from buyers and builders of direct gain passive solar homes interior design criteria either specific to, or emphasized by, passive solar buildings are investigated. Problems of high sunlight penetration, secondary illumination, material selection, sound control and psychology are approached. Material deterioration, fading, glare, noise, and a sense of spacial confinement can be minimized, contributing to the appeal and saleability of passive solar homes.

  19. Labor Costs and Foreign Direct Investment: A Panel VAR Approach

    Bahar Bayraktar-Sağlam; Selin Sayek Böke

    2017-01-01

    This paper examines the endogenous interaction between labor costs and Foreign Direct Investment (FDI) in the OECD countries via the Panel VAR approach under system GMM estimates for the period 1995–2009. The available data allows identifying the relevance of the components of labor costs, and allows a detailed analysis across different sectors. Empirical findings have revealed that sectoral composition of FDI and the decomposition of labor costs play a significant role in investigating the d...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  5. Alternative approach for Article 5. Energie Efficiency Directive; Alternatieve aanpak artikel 5. Energy Efficiency Directive

    Menkveld, M.; Jablonska, B. [ECN Beleidsstudies, Petten (Netherlands)

    2013-05-15

    Article 5 of the Energy Efficiency Directive (EED) is an annual obligation to renovate 3% of the building stock of central government. After renovation the buildings will meet the minimum energy performance requirements laid down in Article 4 of the EPBD. The Directive gives room to an alternative approach to achieve the same savings. The Ministry of Interior Affairs has asked ECN to assist with this alternative approach. ECN calculated what saving are achieved with the 3% renovation obligation under the directive. Then ECN looked for the possibilities for an alternative approach to achieve the same savings [Dutch] In artikel 5 van de Energie Efficiency Directive (EED) staat een verplichting om jaarlijks 3% van de gebouwvoorraad van de centrale overheid te renoveren. Die 3% van de gebouwvoorraad moet na renovatie voldoen aan de minimum eisen inzake energieprestatie die door het betreffende lidstaat zijn vastgelegd op grond van artikel 4 in de EPBD. De verplichting betreft gebouwen die in bezit en in gebruik zijn van de rijksoverheid met een gebruiksoppervlakte groter dan 500 m{sup 2}, vanaf juli 2015 groter dan 250 m{sup 2}. De gebouwen die eigendom zijn van de Rijksgebouwendienst betreft kantoren van rijksdiensten, gerechtsgebouwen, gebouwen van douane en politie en gevangenissen. Van de gebouwen van Defensie hoeven alleen kantoren en legeringsgebouwen aan de verplichting te voldoen.

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

    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.

  7. A Modeling Approach for Plastic-Metal Laser Direct Joining

    Lutey, Adrian H. A.; Fortunato, Alessandro; Ascari, Alessandro; Romoli, Luca

    2017-09-01

    Laser processing has been identified as a feasible approach to direct joining of metal and plastic components without the need for adhesives or mechanical fasteners. The present work sees development of a modeling approach for conduction and transmission laser direct joining of these materials based on multi-layer optical propagation theory and numerical heat flow simulation. The scope of this methodology is to predict process outcomes based on the calculated joint interface and upper surface temperatures. Three representative cases are considered for model verification, including conduction joining of PBT and aluminum alloy, transmission joining of optically transparent PET and stainless steel, and transmission joining of semi-transparent PA 66 and stainless steel. Conduction direct laser joining experiments are performed on black PBT and 6082 anticorodal aluminum alloy, achieving shear loads of over 2000 N with specimens of 2 mm thickness and 25 mm width. Comparison with simulation results shows that consistently high strength is achieved where the peak interface temperature is above the plastic degradation temperature. Comparison of transmission joining simulations and published experimental results confirms these findings and highlights the influence of plastic layer optical absorption on process feasibility.

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

    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.

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

    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.

    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

    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. An approach of community evolution based on gravitational relationship refactoring in dynamic networks

    Yin, Guisheng; Chi, Kuo; Dong, Yuxin; Dong, Hongbin

    2017-01-01

    In this paper, an approach of community evolution based on gravitational relationship refactoring between the nodes in a dynamic network is proposed, and it can be used to simulate the process of community evolution. A static community detection algorithm and a dynamic community evolution algorithm are included in the approach. At first, communities are initialized by constructing the core nodes chains, the nodes can be iteratively searched and divided into corresponding communities via the static community detection algorithm. For a dynamic network, an evolutionary process is divided into three phases, and behaviors of community evolution can be judged according to the changing situation of the core nodes chain in each community. Experiments show that the proposed approach can achieve accuracy and availability in the synthetic and real world networks. - Highlights: • The proposed approach considers both the static community detection and dynamic community evolution. • The approach of community evolution can identify the whole 6 common evolution events. • The proposed approach can judge the evolutionary events according to the variations of the core nodes chains.

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

    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.

  14. Labor Costs and Foreign Direct Investment: A Panel VAR Approach

    Bahar Bayraktar-Sağlam

    2017-09-01

    Full Text Available This paper examines the endogenous interaction between labor costs and Foreign Direct Investment (FDI in the OECD countries via the Panel VAR approach under system GMM estimates for the period 1995–2009. The available data allows identifying the relevance of the components of labor costs, and allows a detailed analysis across different sectors. Empirical findings have revealed that sectoral composition of FDI and the decomposition of labor costs play a significant role in investigating the dynamic association between labor costs and FDI. Further, results suggest that labor market policies should focus on productivity-enhancing tools in addition to price hindering tools.

  15. Approaching direct optimization of as-built lens performance

    McGuire, James P.; Kuper, Thomas G.

    2012-10-01

    We describe a method approaching direct optimization of the rms wavefront error of a lens including tolerances. By including the effect of tolerances in the error function, the designer can choose to improve the as-built performance with a fixed set of tolerances and/or reduce the cost of production lenses with looser tolerances. The method relies on the speed of differential tolerance analysis and has recently become practical due to the combination of continuing increases in computer hardware speed and multiple core processing We illustrate the method's use on a Cooke triplet, a double Gauss, and two plastic mobile phone camera lenses.

  16. Material inhomogeneities and their evolution a geometric approach

    Epstein, Marcelo

    2007-01-01

    Presents a unified treatment of the inhomogeneity theory using some of the tools of modern differential geometry. This book deals with the geometrical description of uniform bodies and their homogeneity conditions. It also develops a theory of material evolution and discusses its relevance in various applied contexts.

  17. Early Stages of the Evolution of Life: a Cybernetic Approach

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  18. Direct approach for bioprocess optimization in a continuous flat-bed photobioreactor system.

    Kwon, Jong-Hee; Rögner, Matthias; Rexroth, Sascha

    2012-11-30

    Application of photosynthetic micro-organisms, such as cyanobacteria and green algae, for the carbon neutral energy production raises the need for cost-efficient photobiological processes. Optimization of these processes requires permanent control of many independent and mutably dependent parameters, for which a continuous cultivation approach has significant advantages. As central factors like the cell density can be kept constant by turbidostatic control, light intensity and iron content with its strong impact on productivity can be optimized. Both are key parameters due to their strong dependence on photosynthetic activity. Here we introduce an engineered low-cost 5 L flat-plate photobioreactor in combination with a simple and efficient optimization procedure for continuous photo-cultivation of microalgae. Based on direct determination of the growth rate at constant cell densities and the continuous measurement of O₂ evolution, stress conditions and their effect on the photosynthetic productivity can be directly observed. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Direct percutaneous transaortic approach for treatment of aortic pseudoaneurysms.

    Pirelli, Luigi; Kliger, Chad; Fontana, Gregory P; Ruiz, Carlos E

    2015-05-01

    Aortic pseudoaneurysms (APAs) can develop months or years after aortic and cardiac surgery. If not treated appropriately, APAs can lead to fatal complications and ultimately death. We describe a case of a 61-year old patient with a diagnosed large pseudoaneurysm 5 years after his aortic valve surgery, who was treated with a novel transcatheter direct transaortic approach. The patient had dilated cardiomyopathy with an APA adjacent to the lower sternal plate. An Amplatzer septal occlusion device followed by coils was delivered transcutaneously through the APA to close its neck and fill the false aneurysm, respectively. Triple fusion multimodality imaging was used to guide the placement of the occlusion devices. The merging of computed tomography (CT) and echocardiography with real-time fluoroscopy was fundamental in procedural planning and guidance. Post-procedural transoesophageal echocardiogram (TOE) and CT angiography showed complete exclusion of the APA. A direct transaortic approach is a valid option for closure of an APA if the surgical risk is prohibitive, and the use of triple fusion technology is an essential tool in the hands of interventionalists and surgeons for preoperative planning and conduction of these procedures. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Statistical approach to thermal evolution of neutron stars

    Beznogov, M V; Yakovlev, D G

    2015-01-01

    Studying thermal evolution of neutron stars (NSs) is one of a few ways to investigate the properties of superdense matter in their cores. We study the cooling of isolated NSs (INSs) and deep crustal heating of transiently accreting NSs in X-ray transients (XRTs, binary systems with low-mass companions). Currently, nearly 50 of such NSs are observed, and one can apply statistical methods to analyze the whole dataset. We propose a method for such analysis based on thermal evolution theory for individual stars and on averaging the results over NS mass distributions. We calculate the distributions of INSs and accreting NSs (ANSs) in XRTs over cooling and heating diagrams respectively. Comparing theoretical and observational distributions one can infer information on physical properties of superdense matter and on mass distributions of INSs and ANSs. (paper)

  1. EVOLUTION OF THEORETICAL APPROACHES TO THE DEFINITION OF THE CATEGORY “PERSONNEL POTENTIAL”

    Аlexandra Deshchenko

    2016-02-01

    Full Text Available The article describes the evolution of theoretical approaches to definition of the category «personnel potential» based on the analysis of approaches to definition of the conceptual apparatus of labor Economics, including such categories as: labor force, labor resources, labor potential, human resources, human capital, human capital different authors. The analysis of the evolution of the terms in accordance with the stages of development of a society.

  2. Biological evolution of replicator systems: towards a quantitative approach.

    Martin, Osmel; Horvath, J E

    2013-04-01

    The aim of this work is to study the features of a simple replicator chemical model of the relation between kinetic stability and entropy production under the action of external perturbations. We quantitatively explore the different paths leading to evolution in a toy model where two independent replicators compete for the same substrate. To do that, the same scenario described originally by Pross (J Phys Org Chem 17:312-316, 2004) is revised and new criteria to define the kinetic stability are proposed. Our results suggest that fast replicator populations are continually favored by the effects of strong stochastic environmental fluctuations capable to determine the global population, the former assumed to be the only acting evolution force. We demonstrate that the process is continually driven by strong perturbations only, and that population crashes may be useful proxies for these catastrophic environmental fluctuations. As expected, such behavior is particularly enhanced under very large scale perturbations, suggesting a likely dynamical footprint in the recovery patterns of new species after mass extinction events in the Earth's geological past. Furthermore, the hypothesis that natural selection always favors the faster processes may give theoretical support to different studies that claim the applicability of maximum principles like the Maximum Metabolic Flux (MMF) or Maximum Entropy Productions Principle (MEPP), seen as the main goal of biological evolution.

  3. The Institutional Approach for Modeling the Evolution of Human Societies.

    Powers, Simon T

    2018-01-01

    Artificial life is concerned with understanding the dynamics of human societies. A defining feature of any society is its institutions. However, defining exactly what an institution is has proven difficult, with authors often talking past each other. This article presents a dynamic model of institutions, which views them as political game forms that generate the rules of a group's economic interactions. Unlike most prior work, the framework presented here allows for the construction of explicit models of the evolution of institutional rules. It takes account of the fact that group members are likely to try to create rules that benefit themselves. Following from this, it allows us to determine the conditions under which self-interested individuals will create institutional rules that support cooperation-for example, that prevent a tragedy of the commons. The article finishes with an example of how a model of the evolution of institutional rewards and punishments for promoting cooperation can be created. It is intended that this framework will allow artificial life researchers to examine how human groups can themselves create conditions for cooperation. This will help provide a better understanding of historical human social evolution, and facilitate the resolution of pressing societal social dilemmas.

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

    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.

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

    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

  6. Coastal Foredune Evolution, Part 2: Modeling Approaches for Meso-Scale Morphologic Evolution

    2017-03-01

    for Meso-Scale Morphologic Evolution by Margaret L. Palmsten1, Katherine L. Brodie2, and Nicholas J. Spore2 PURPOSE: This Coastal and Hydraulics ...managers because foredunes provide ecosystem services and can reduce storm damages to coastal infrastructure, both of which increase the resiliency...MS 2 U.S. Army Engineer Research and Development Center, Coastal and Hydraulics Laboratory, Duck, NC ERDC/CHL CHETN-II-57 March 2017 2 models of

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

    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

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

    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.

  9. The evolution of "Life": A Metadarwinian integrative approach.

    De Loof, Arnold

    2017-01-01

    It is undeniably very logical to first formulate an unambiguous definition of "Life" before engaging in defining the parameters instrumental to Life's evolution. Because nearly everybody assumes, erroneously in my opinion, that catching Life's essence in a single sentence is impossible, this way of thinking remained largely unexplored in evolutionary theory. Upon analyzing what exactly happens at the transition from "still alive" to "just dead," the following definition emerged. What we call "Life" (L) is an activity . It is nothing other than the total sum (∑) of all communication acts (C) executed, at moment t, by entities organized as sender-receiver compartments: L = ∑C Such "living" entities are self-electrifying and talking ( = communicating) aggregates of fossil stardust operating in an environment heavily polluted by toxic calcium. Communication is a multifaceted, complex process that is seldom well explained in introductory textbooks of biology. Communication is instrumental to adaptation because, at the cellular level, any act of communication is in fact a problem-solving act. It can be logically deduced that not Natural Selection itself but communication/problem-solving activity preceding selection is the universal driving force of evolution. This is against what textbooks usually claim, although doubt on the status of Natural Selection as driving force has been around for long. Finally, adopting the sender-receiver with its 2 memory systems (genetic and cognitive, both with their own rules) and 2 types of progeny ("physical children" and "pupils") as the universal unit of architecture and function of all living entities, also enables the seamless integration of cultural and organic evolution, another long-standing tough problem in evolutionary theory. Paraphrasing Theodosius Dobzhansky, the very essence of biology is: "Nothing in biology and evolutionary theory makes sense except in the light of the ability of living matter to communicate, and by

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

    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

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

    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.

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

    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.

  13. Emotional and Spiritual Quotient Approach Improve Biology Education Students’ Acceptance of Evolution Theory

    Darussyamsu, R.; Fadilah, M.; Putri, D. H.

    2018-04-01

    Emotional and spiritual aspect is one of main factors that influence students’ acceptance of a theory. This study aim to measure university students’ acceptance of evolution by learns evolution using emotional and spiritual quotient (ESQ) approach. This is a quasi-experimental research using one shot case study design with the subject 36 biology educational students at Biology Department, Faculty of Mathematics and Natural Science, Universitas Negeri Padang. Data collected using the MATE instrument by Rutledge and Warden (2000) after the students learn evolution for eight meetings since January until March 2017. The result showed that by learning evolution theory combine with ESQ aspects increase students acceptance from very low become moderate acceptance. It concluded that ESQ aspects can improve students’ acceptance of evolution. Any criteria depend on it are discussed.

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

    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

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

    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.

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

    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.

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

    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....

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

    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.

  19. Phenylalanine ammonia-lyase through evolution: A bioinformatic approach

    Shiva Hemmati

    2015-03-01

    Full Text Available Phenylalanine ammonia-lyase (PAL is the first entry enzyme of the phenylpropanoid pathway that converts phenylalanine to cinnamic acid which is the precursor of various secondary metabolites. PAL is recently formulated for phenylketonuric patients in pegylated forms; therefore, screening a PAL with the highest affinity to the substrate is of a great importance. PAL exists in all higher plants and some fungi and few bacteria. Ancestors of land plants have been adopted by evolving metabolic pathways. A multi-gene family encodes PAL by gene duplication events in most plants. In this study, the taxonomic distribution and phylogeny of pal gene found in land plants, fungi and bacteria have been analyzed. It seems that the ancestor of plants acquired a pal gene via horizontal gene transfer in symbioses with bacteria and fungi. Gymnosperms have kept a diverse set of pal genes that arose from gene duplication events. In angiosperms, after the divergence of dicotyledons from monocots, pal genes were duplicated many times. The close paralogues of pal genes in some species indicate expansion of gene families after the divergence in plant pal gene evolution. Interestingly, some of the plant pals clustered by species in a way that pals within one species are more closely related to each other than to homologs in the other species which indicates this duplication event occurred more recently.

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

    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.

  1. Direct Problem-Based Learning (DPBL): A Framework for Integrating Direct Instruction and Problem-Based Learning Approach

    Winarno, Sri; Muthu, Kalaiarasi Sonai; Ling, Lew Sook

    2018-01-01

    Direct instruction approach has been widely used in higher education. Many studies revealed that direct instruction improved students' knowledge. The characteristics of direct instruction include the subject delivered through face-to-face interaction with the lecturers and materials that sequenced deliberately and taught explicitly. However,…

  2. Axial and parity anomalies and vacuum charge: A direct approach

    Boyanovsky, D.; Blankenbecler, R.

    1985-01-01

    We study the axial and parity anomalies in Abelian gauge theories using the direct yet intuitive approach of counting the relative number of states of one chirality with respect to the other. A fundamental gauge-invariant quantity, the determinantal ratio, is introduced for this purpose. We find that the number of states is conserved and that the gauge fields differentially phase shift states of opposite chirality at infinite energies. This implies a relative flow of states at very large energies which must be compensated by a rearrangement of the density of states at finite energies. We then derive a sum rule which yields two alternative formulas for the index of a Dirac operator. One expresses the index in terms of its high-energy behavior, and the other in terms of the low-energy properties; these are the ''zero modes'' of definite chirality. Two examples are worked out in detail to clarify our general result. The physics of the axial anomaly is shown to translate into that of the parity anomaly in 2+1 dimensions, in which parity and chirality have interchanged roles. We also analyze the vacuum charge in regard to its high- and low-energy origin. The possibility of spectral flow is formulated and briefly discussed. In short, we provide a physical interpretation of certain mathematical indices, relate them to an extended version of Levinson's theorem of potential scattering, and simplify their evaluation

  3. Evolution of the the ART approach: highlights and achievements

    Jo E. Frencken

    2009-01-01

    Full Text Available Atraumatic Restorative Treatment (ART was initiated in the mid-eighties in Tanzania in response to an inappropriately functioning community oral health programme that was based on western health care models and western technology. The approach has evolved to its present standing as an effective minimal intervention approach mainly because the originators anticipated the great potential of ART to alleviate inequality in oral health care, and because they recognised the need to carry out research to investigate its effectiveness and applicability. Twenty-five years later, ART was accepted by the World Health Organisation (1994 and the FDI World Dental Federation (2002. It is included in textbooks on cariology, restorative dentistry and minimal intervention dentistry. It is being systematically introduced into public oral health service systems in a number of low- and middle income countries. Private practitioners use it. Many publications related to aspects of ART have been published and many more will follow. To achieve quality results with ART one has to attend well-conducted and sufficiently long training courses, preferably in combination with other caries preventive strategies. ART should, therefore, not be considered in isolation and must be part of an evidence-based approach to oral health with a strong foundation based on prevention.

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

    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.

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

    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

  6. A non-deterministic approach to forecasting the trophic evolution of lakes

    Roberto Bertoni

    2016-03-01

    Full Text Available Limnologists have long recognized that one of the goals of their discipline is to increase its predictive capability. In recent years, the role of prediction in applied ecology escalated, mainly due to man’s increased ability to change the biosphere. Such alterations often came with unplanned and noticeably negative side effects mushrooming from lack of proper attention to long-term consequences. Regression analysis of common limnological parameters has been successfully applied to develop predictive models relating the variability of limnological parameters to specific key causes. These approaches, though, are biased by the requirement of a priori cause-relation assumption, oftentimes difficult to find in the complex, nonlinear relationships entangling ecological data. A set of quantitative tools that can help addressing current environmental challenges avoiding such restrictions is currently being researched and developed within the framework of ecological informatics. One of these approaches attempting to model the relationship between a set of inputs and known outputs, is based on genetic algorithms and programming (GP. This stochastic optimization tool is based on the process of evolution in natural systems and was inspired by a direct analogy to sexual reproduction and Charles Darwin’s principle of natural selection. GP works through genetic algorithms that use selection and recombination operators to generate a population of equations. Thanks to a 25-years long time-series of regular limnological data, the deep, large, oligotrophic Lake Maggiore (Northern Italy is the ideal case study to test the predictive ability of GP. Testing of GP on the multi-year data series of this lake has allowed us to verify the forecasting efficacy of the models emerging from GP application. In addition, this non-deterministic approach leads to the discovery of non-obvious relationships between variables and enabled the formulation of new stochastic models.

  7. Modelling of nanoparticles: approaches to morphology and evolution

    Barnard, A S

    2010-01-01

    As we learn more about the physics, chemistry and engineering of materials at the nanoscale, we find that the development of a complete understanding is not (in general) possible using one technique alone. Computer simulations provide a very valuable addition to our scientific repertoire, but it is not immediately intuitive which of the many methods available are right for a given problem. In this paper, various computational approaches are described as they apply to the study of the structure and formation of discrete inorganic nanoparticles. To illustrate how these methods are best used, results of studies from many research groups are reviewed, and informal case studies are constructed on carbon, titania and gold nanoparticles.

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

    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.

  9. Rural credit in Brazil: contrat's evolution at an institutional approach

    Luciana Florêncio de Almeida

    2009-03-01

    Full Text Available This article outlines a New Institutional Economics’ approach of rural credit. The mainstream relies in the understanding that the rural credit contracts are hybrid forms in response to the agrichain´s complexity. The object of the research was operational credit contract for soybeans farms. The research consisted on qualitative researches in the extent that they sought to comprehend in a more profound level the rules of game for the rural financing contracting environment based on the economic agent’s perceptions. The results highlighted the agent’s perception that the judicial system is not strong enough to performance an efficient enforcement of the contracts. In response to this institutional challenge, the agents and the government manage adaptations in the contracts, which has been successful in the agent’s point of view. In the other hand, the informational system has showed weaknesses in protecting the creditor’s right. This scenario open breaches to opportunist actions and adverse selection. In order to mitigate these problems the agents govern interdependent transactions as a tool for risk sharing.

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

    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.

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

    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.

  12. Quantitative approaches for profit maximization in direct marketing

    van der Scheer, H.R.

    1998-01-01

    An effective direct marketing campaign aims at selecting those targets, offer and communication elements - at the right time - that maximize the net profits. The list of individuals to be mailed, i.e. the targets, is considered to be the most important component. Therefore, a large amount of direct

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

  20. Study of the microdoppler signature of a bicyclist for different directions of approach

    Rodriguez-Hervas, Berta; Maile, Michael; Flores, Benjamin C.

    2015-05-01

    The successful implementation of autonomous driving in an urban setting depends on the ability of the environment perception system to correctly classify vulnerable road users such as pedestrians and bicyclists in dense, complex scenarios. Self-driving vehicles include sensor systems such as cameras, lidars, and radars to enable decision making. Among these systems, radars are particularly relevant due to their operational robustness under adverse weather and night light conditions. Classification of pedestrian and car in urban settings using automotive radar has been widely investigated, suggesting that micro-Doppler signatures are useful for target discrimination. Our objective is to analyze and study the micro-Doppler signature of bicyclists approaching a vehicle from different directions in order to establish the basis of a classification criterion to distinguish bicycles from other targets including clutter. The micro-Doppler signature is obtained by grouping individual reflecting points using a clustering algorithm and observing the evolution of all the points belonging to an object in the Doppler domain over time. A comparison is then made with simulated data that uses a kinematic model of bicyclists' movement. The suitability of the micro-Doppler bicyclist signature as a classification feature is determined by comparing it to those belonging to cars and pedestrians approaching the automotive radar system.

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

    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).

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

    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).

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

    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.

  4. Direction-Dependence Analysis: A Confirmatory Approach for Testing Directional Theories

    Wiedermann, Wolfgang; von Eye, Alexander

    2015-01-01

    The concept of direction dependence has attracted growing attention due to its potential to help decide which of two competing linear regression models (X ? Y or Y ? X) is more likely to reflect the correct causal flow. Several tests have been proposed to evaluate hypotheses compatible with direction dependence. In this issue, Thoemmes (2015)…

  5. A Trajectory Generation Approach for Payload Directed Flight

    Ippolito, Corey A.; Yeh, Yoo-Hsiu

    2009-01-01

    Presently, flight systems designed to perform payload-centric maneuvers require preconstructed procedures and special hand-tuned guidance modes. To enable intelligent maneuvering via strong coupling between the goals of payload-directed flight and the autopilot functions, there exists a need to rethink traditional autopilot design and function. Research into payload directed flight examines sensor and payload-centric autopilot modes, architectures, and algorithms that provide layers of intelligent guidance, navigation and control for flight vehicles to achieve mission goals related to the payload sensors, taking into account various constraints such as the performance limitations of the aircraft, target tracking and estimation, obstacle avoidance, and constraint satisfaction. Payload directed flight requires a methodology for accurate trajectory planning that lets the system anticipate expected return from a suite of onboard sensors. This paper presents an extension to the existing techniques used in the literature to quickly and accurately plan flight trajectories that predict and optimize the expected return of onboard payload sensors.

  6. Impact of time and space evolution of ion tracks in nonvolatile memory cells approaching nanoscale

    Cellere, G.; Paccagnella, A.; Murat, M.; Barak, J.; Akkerman, A.; Harboe-Sorensen, R.; Virtanen, A.; Visconti, A.; Bonanomi, M.

    2010-01-01

    Swift heavy ions impacting on matter lose energy through the creation of dense tracks of charges. The study of the space and time evolution of energy exchange allows understanding the single event effects behavior in advanced microelectronic devices. In particular, the shrinking of minimum feature size of most advanced memory devices makes them very interesting test vehicles to study these effects since the device and the track dimensions are comparable; hence, measured effects are directly correlated with the time and space evolution of the energy release. In this work we are studying the time and space evolution of ion tracks by using advanced non volatile memories and Monte Carlo simulations. Experimental results are very well explained by the theoretical calculations.

  7. Pechukas-Yukawa approach to the evolution of the quantum state of a parametrically perturbed system

    Qureshi, Mumnuna A.; Zhong, Johnny; Qureshi, Zihad; Mason, Peter; Betouras, Joseph J.; Zagoskin, Alexandre M.

    2018-03-01

    We consider the evolution of the quantum states of a Hamiltonian that is parametrically perturbed via a term proportional to the adiabatic parameter λ (t ) . Starting with the Pechukas-Yukawa mapping of the energy eigenvalue evolution in a generalized Calogero-Sutherland model of a one-dimensional classical gas, we consider the adiabatic approximation with two different expansions of the quantum state in powers of d λ /d t and compare them with a direct numerical simulation. We show that one of these expansions (Magnus series) is especially convenient for the description of nonadiabatic evolution of the system. Applying the expansion to the exact cover 3-satisfiability problem, we obtain the occupation dynamics, which provides insight into the population of states and sources of decoherence in a quantum system.

  8. A novel optimization design approach for Contourlet directional filter banks

    Zhang, Songjun; Yang, Guoan; Cheng, Zhengxing; van de Wetering, H.M.M.; Ikuta, Chihiro; Nishio, Yoshifumi

    2014-01-01

    A Contourlet transform, an expansion of a wavelet transform, is a double filter bank structure composed of Laplacian Pyramid and directional filter banks. Several wavelet filters of preferable performance have been developed for wavelet transforms, e.g. CDF (Cohen, Daubechies and Feauveau) 9/7

  9. A Unifying Approach to Goal-Directed Evaluation

    Danvy, Olivier; Rhiger, Morten; Grobauer, Bernd

    2001-01-01

    Goal-directed evaluation, as embodied in Icon and Snobol, is built on the notions of backtracking and of generating successive results, and therefore it has always been something of a challenge to specify and implement. In this article, we address this challenge using computational monads and par...

  10. Conceptualizing strategic environmental assessment: Principles, approaches and research directions

    Noble, Bram, E-mail: b.noble@usask.ca [Department of Geography and Planning, and School of Environment and Sustainability, University of Saskatchewan, 117 Science Place, Saskatoon, Saskatchewan S7N 5A5 (Canada); Nwanekezie, Kelechi [Department of Geography and Planning, University of Saskatchewan, 117 Science Place, Saskatoon, Saskatchewan S7N 5A5 (Canada)

    2017-01-15

    Increasing emphasis has been placed in recent years on transitioning strategic environmental assessment (SEA) away from its environmental impact assessment (EIA) roots. Scholars have argued the need to conceptualize SEA as a process designed to facilitate strategic thinking, thus enabling transitions toward sustainability. The practice of SEA, however, remains deeply rooted in the EIA tradition and scholars and practitioners often appear divided on the nature and purpose of SEA. This paper revisits the strategic principles of SEA and conceptualizes SEA as a multi-faceted and multi-dimensional assessment process. It is suggested that SEA can be conceptualized as series of approaches operating along a spectrum from less to more strategic – from impact assessment-based to strategy-based – with each approach to SEA differentiated by the specific objectives of SEA application and the extent to which strategic principles are reflected in its design and implementation. Advancing the effectiveness of SEA requires a continued research agenda focused on improving the traditional SEA approach, as a tool to assess the impacts of policies, plans and programs (PPPs). Realizing the full potential of SEA, however, requires a new research agenda — one focused on the development and testing of a deliberative governance approach to SEA that can facilitate strategic innovations in PPP formulation and drive transitions in short-term policy and initiatives based on longer-term thinking. - Highlights: • SEA facilitates strategic thinking, enabling transitions toward sustainability. • SEA is conceptualized as a spectrum of approaches, from IA-based to strategy-based. • Each approach variably emphasizes strategic principles in its design and practice. • There is no one conceptualization of SEA that is best, SEA is fit for PPP purpose. • Research is needed to advance SEA to facilitate strategic PPP transformations.

  11. Conceptualizing strategic environmental assessment: Principles, approaches and research directions

    Noble, Bram; Nwanekezie, Kelechi

    2017-01-01

    Increasing emphasis has been placed in recent years on transitioning strategic environmental assessment (SEA) away from its environmental impact assessment (EIA) roots. Scholars have argued the need to conceptualize SEA as a process designed to facilitate strategic thinking, thus enabling transitions toward sustainability. The practice of SEA, however, remains deeply rooted in the EIA tradition and scholars and practitioners often appear divided on the nature and purpose of SEA. This paper revisits the strategic principles of SEA and conceptualizes SEA as a multi-faceted and multi-dimensional assessment process. It is suggested that SEA can be conceptualized as series of approaches operating along a spectrum from less to more strategic – from impact assessment-based to strategy-based – with each approach to SEA differentiated by the specific objectives of SEA application and the extent to which strategic principles are reflected in its design and implementation. Advancing the effectiveness of SEA requires a continued research agenda focused on improving the traditional SEA approach, as a tool to assess the impacts of policies, plans and programs (PPPs). Realizing the full potential of SEA, however, requires a new research agenda — one focused on the development and testing of a deliberative governance approach to SEA that can facilitate strategic innovations in PPP formulation and drive transitions in short-term policy and initiatives based on longer-term thinking. - Highlights: • SEA facilitates strategic thinking, enabling transitions toward sustainability. • SEA is conceptualized as a spectrum of approaches, from IA-based to strategy-based. • Each approach variably emphasizes strategic principles in its design and practice. • There is no one conceptualization of SEA that is best, SEA is fit for PPP purpose. • Research is needed to advance SEA to facilitate strategic PPP transformations.

  12. Pointing and the Evolution of Language: An Applied Evolutionary Epistemological Approach

    Nathalie Gontier

    2013-07-01

    Full Text Available Numerous evolutionary linguists have indicated that human pointing behaviour might be associated with the evolution of language. At an ontogenetic level, and in normal individuals, pointing develops spontaneously and the onset of human pointing precedes as well as facilitates phases in speech and language development. Phylogenetically, pointing behaviour might have preceded and facilitated the evolutionary origin of both gestural and vocal language. Contrary to wild non-human primates, captive and human-reared nonhuman primates also demonstrate pointing behaviour. In this article, we analyse the debates on pointing and its role it might have played in language evolution from a meta-level. From within an Applied Evolutionary Epistemological approach, we examine how exactly we can determine whether pointing has been a unit, a level or a mechanism in language evolution.

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

    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.

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

    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.

  15. Efficiency analysis of Chinese industry: A directional distance function approach

    Watanabe, Michio; Tanaka, Katsuya

    2007-01-01

    Two efficiency measures of Chinese industry were estimated at the provincial level from 1994 to 2002, using a directional output distance function. One is a traditional efficiency measure that considers only desirable output, while the other considers both desirable and undesirable outputs simultaneously. A comparison of the two measures revealed that efficiency levels are biased only if desirable output is considered. Five coastal provinces/municipalities that have attracted a large amount of foreign direct investment are found to be the most efficient when only desirable output is considered, and also when both desirable and undesirable outputs are considered. However, omitting undesirable output tends to lead to an overestimate of industrial efficiency levels in Shandong, Sichuan, and Hebei provinces. We also found that a province's industrial structure has significant effects on its efficiency levels

  16. A Unifying Approach to Goal-Directed Evaluation

    Danvy, Olivier; Grobauer, Bernd; Rhiger, Morten

    2001-01-01

    semantics coincides with Gudeman’s continuation semantics of Icon. We then compile Icon programs by specializing their interpreter (i.e., by using the first Futamura projection), using type-directed partial evaluation. Through various back ends, including a run-time code generator, we generate ML code, C......Goal-directed evaluation, as embodied in Icon and Snobol, is built on the notions of backtracking and of generating successive results, and therefore it has always been something of a challenge to specify and implement. In this article, we address this challenge using computational monads...... code, and OCaml byte code. Binding-time analysis and partial evaluation of the continuation-based interpreter automatically give rise to C programs that coincide with the result of Proebsting’s optimized compiler....

  17. A new approach for multicriticality in directed and diode percolation

    Tsallis, C.; Boston Univ., MA; Redner, S.

    1983-01-01

    A new and very simple model for treating directed and more general diode percolation problems is presented, by allowing neighboring sites to be joined by up to two independent bonds of opposite orientations. A generalized 'break-collapse' method is developed to calculate renormalization group recursion relations. On the square lattice, a very symmetric phase diagram is obtained which displays multicritical percolation phenomena, and a variety of interesting conductivity transitions are predicted. (Author) [pt

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

    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.

  19. Reliability-redundancy optimization by means of a chaotic differential evolution approach

    Coelho, Leandro dos Santos

    2009-01-01

    The reliability design is related to the performance analysis of many engineering systems. The reliability-redundancy optimization problems involve selection of components with multiple choices and redundancy levels that produce maximum benefits, can be subject to the cost, weight, and volume constraints. Classical mathematical methods have failed in handling nonconvexities and nonsmoothness in optimization problems. As an alternative to the classical optimization approaches, the meta-heuristics have been given much attention by many researchers due to their ability to find an almost global optimal solution in reliability-redundancy optimization problems. Evolutionary algorithms (EAs) - paradigms of evolutionary computation field - are stochastic and robust meta-heuristics useful to solve reliability-redundancy optimization problems. EAs such as genetic algorithm, evolutionary programming, evolution strategies and differential evolution are being used to find global or near global optimal solution. A differential evolution approach based on chaotic sequences using Lozi's map for reliability-redundancy optimization problems is proposed in this paper. The proposed method has a fast convergence rate but also maintains the diversity of the population so as to escape from local optima. An application example in reliability-redundancy optimization based on the overspeed protection system of a gas turbine is given to show its usefulness and efficiency. Simulation results show that the application of deterministic chaotic sequences instead of random sequences is a possible strategy to improve the performance of differential evolution.

  20. Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution.

    Smith, Silvia E; Showers-Corneli, Patrice; Dardenne, Caitlin N; Harpending, Henry H; Martin, Darren P; Beiko, Robert G

    2012-01-01

    The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer (M. abscessus to Segniliparus and M. smegmatis to Streptomyces), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case (M. vanbaalenii to Streptomyces) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is

  1. Direct anticoagulants and nursing: an approach from patient's safety.

    Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan

    In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  2. Opal shell structures: direct assembly versus inversion approach.

    Deng, Tian-Song; Sharifi, Parvin; Marlow, Frank

    2013-09-16

    Opal shell structures can be fabricated in two ways: By direct assembly from hollow spheres (hs-opal) or by infiltration of precursors into opal templates and inversion. The resulting lattice disturbances were characterized by scanning electron microscopy (SEM), optical microscopy, and transmission spectra. The hs-opal system shows much lower disturbances, for example, a lower number of cracks and lattice deformations. The strong suppression of crack formation in one of these inverse opal structures can be considered as promising candidates for the fabrication of more perfect photonic crystals. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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.

    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.

  4. Cache and memory hierarchy design a performance directed approach

    Przybylski, Steven A

    1991-01-01

    An authoritative book for hardware and software designers. Caches are by far the simplest and most effective mechanism for improving computer performance. This innovative book exposes the characteristics of performance-optimal single and multi-level cache hierarchies by approaching the cache design process through the novel perspective of minimizing execution times. It presents useful data on the relative performance of a wide spectrum of machines and offers empirical and analytical evaluations of the underlying phenomena. This book will help computer professionals appreciate the impact of ca

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

    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

  6. Determinants of Foreign Direct Investment in Romania: a Quantitative Approach

    Calcedonia Enache

    2017-02-01

    Full Text Available This study aims to examine the dynamic relationship between foreign direct investments (FDI and economic growth, using the Structural Vector Autoregressive model, in the period 2007-2014. The results of the econometric model show that the trajectory of FDI has its own origins, with reduced influences from economic growth. Another important conclusion is that there is a unidirectional causal relationship from the economic growth towards FDI, more precisely the influence of FDI on economic growth does not have a systematic, anticipatory nature. These results were achieved in the condition that, in the analyzed period, the net inflows of FDI were influenced by the lack of certainty on the sustainable re-launching of the economic growth both domestically and internationally, the segmentation of the financial market, the domestic structural reforms.

  7. Current approaches and future directions in the treatment of leprosy

    Worobec SM

    2012-08-01

    Full Text Available Sophie M WorobecDepartment of Dermatology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: This review surveys current treatments and future treatment trends in leprosy from a clinical perspective. The World Health Organization provides a multidrug treatment regimen that targets the Mycobacterium leprae bacillus which causes leprosy. Several investigational drugs are available for the treatment of drug-resistant M. leprae. Future directions in leprosy treatment will focus on: the molecular signaling mechanism M. leprae uses to avoid triggering an immune response; prospective studies of the side effects experienced during multiple-drug therapy; recognition of relapse rates post-completion of designated treatments; combating multidrug resistance; vaccine development; development of new diagnostic tests; and the implications of the recent discovery of a genetically distinct leprosy-causing bacillus, Mycobacterium lepromatosis.Keywords: epidemiology, leprosy, Hansen’s disease, multidrug resistance, multidrug therapy

  8. Efficient and simple approaches towards direct oxidative esterification of alcohols.

    Ray, Ritwika; Jana, Rahul Dev; Bhadra, Mayukh; Maiti, Debabrata; Lahiri, Goutam Kumar

    2014-11-17

    The present article describes novel oxidative protocols for direct esterification of alcohols. The protocols involve successful demonstrations of both "cross" and "self" esterification of a wide variety of alcohols. The cross-esterification proceeds under a simple transition-metal-free condition, containing catalytic amounts of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)/TBAB (tetra-n-butylammonium bromide) in combination with oxone (potassium peroxo monosulfate) as the oxidant, whereas the self-esterification is achieved through simple induction of Fe(OAc)2 /dipic (dipic=2,6-pyridinedicarboxylic acid) as the active catalyst under an identical oxidizing environment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. RISK AND THE FOREIGN DIRECT INVESTMENT - SYNTHETIC APPROACH

    LĂPĂDUŞI MIHAELA LOREDANA

    2016-06-01

    Full Text Available As part of the international economics flows, FDI always puts a mark on the economic development of a country. The internationalization of a company by investments involves a great many risks, from the lowest to the highest level of involvement. On the basis of these considerations one can assess that the country risk is one of the most important pillars that support the process of internationalization of a company by means of foreign direct investments. Broadly sepaking, country risk is an important component of the overall risk of trading on international levels. In other terms it can be seen as the likelihood of losses resulting from a series of macroeconomic (GDP decline on the long run, inflation increase, economic crises, etc., social (conflicts between social classes, civil wars, riots, etc. and political events (wars, territorial claims, conflicts of interest, etc.. In order to identify the main country risk factors that influence the decision of corporations to invest abroad, AT Kearney (2004 performed an extensive survery among multinational corporations. Those risk factors that were most frequently mentioned included government regulations (64%, country financial risk (60%, currency or interest rate volatility (51% and political and social disturbance (46%.[11] The purpose of this article is to highlight a number of important factors that may affect the realization of a foreign direct investment, in other terms to influence "go-no-go" decisions, that is to invest or not to invest. Also, through the analysis of the influence of country risk over FDI one aims at evaluating the relationship between risk and potential gain resulting from conducting the respective business. The purpose of this article is an attempt to identify and develop aspects that outline a number of risk factors of influence over FDI.

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

    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.

  11. Creating sustainable directions. Collaborative stakeholder approach of governments and businesses

    Keijzers, G.H.J.

    2003-01-01

    In this study it is demonstrated that the increasing complexity of sustainable development processes makes it necessary to intensify the collaboration between public and private parties to ensure effective, committed and enduring change. It is also demonstrated that this applies to both the development of government and business strategies and policies for sustainability. Report is given on research into the development of collaborative stakeholder and consensus-building approach for sustainable development. The emergence of new processes of collaboration and the increased intensity of collaboration between governments, businesses and societal groups is illustrated. The main research questions of this dissertation were formulated as: How does the complex and broadening range of sustainability issues affect policy processes for governments and businesses?; and How can enterprises manage the strategic processes of adapting their resources and capabilities to the evolving sustainability demands from a growing number of stakeholders?

  12. Quality management, a directive approach to patient safety.

    Ayuso-Murillo, Diego; de Andrés-Gimeno, Begoña; Noriega-Matanza, Concha; López-Suárez, Rafael Jesús; Herrera-Peco, Ivan

    Nowadays the implementation of effective quality management systems and external evaluation in healthcare is a necessity to ensure not only transparency in activities related to health but also access to health and patient safety. The key to correctly implementing a quality management system is support from the managers of health facilities, since it is managers who design and communicate to health professionals the strategies of action involved in quality management systems. This article focuses on nursing managers' approach to quality management through the implementation of cycles of continuous improvement, participation of improvement groups, monitoring systems and external evaluation quality models (EFQM, ISO). The implementation of a quality management system will enable preventable adverse effects to be minimized or eliminated, and promote patient safety and safe practice by health professionals. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  13. 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.

    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.

  14. Orbiting binary black hole evolutions with a multipatch high order finite-difference approach

    Pazos, Enrique; Tiglio, Manuel; Duez, Matthew D.; Kidder, Lawrence E.; Teukolsky, Saul A.

    2009-01-01

    We present numerical simulations of orbiting black holes for around 12 cycles, using a high order multipatch approach. Unlike some other approaches, the computational speed scales almost perfectly for thousands of processors. Multipatch methods are an alternative to adaptive mesh refinement, with benefits of simplicity and better scaling for improving the resolution in the wave zone. The results presented here pave the way for multipatch evolutions of black hole-neutron star and neutron star-neutron star binaries, where high resolution grids are needed to resolve details of the matter flow.

  15. Engaging Patients With Advance Directives Using an Information Visualization Approach.

    Woollen, Janet; Bakken, Suzanne

    2016-01-01

    Despite the benefits of advance directives (AD) to patients and care providers, they are often not completed due to lack of patient awareness. The purpose of the current article is to advocate for creation and use of an innovative information visualization (infovisual) as a health communication tool aimed at improving AD dissemination and engagement. The infovisual would promote AD awareness by encouraging patients to learn about their options and inspire contemplation and conversation regarding their end-of-life (EOL) journey. An infovisual may be able to communicate insights that are often communicated in words, but are much more powerfully communicated by example. Furthermore, an infovisual could facilitate vivid understanding of options and inspire the beginning of often difficult conversations among care providers, patients, and loved ones. It may also save clinicians time, as care providers may be able to spend less time explaining details of EOL care options. Use of an infovisual could assist in ensuring a well-planned EOL journey. Copyright 2016, SLACK Incorporated.

  16. New approach for direct chemical synthesis of hexagonal Co nanoparticles

    Abel, Frank M., E-mail: fabel@udel.edu [Physics and Astronomy, University of Delaware (United States); Tzitzios, Vasilis [Institute of Nanoscience and Nanotechnology, NCSR, Demokritos (Greece); Hadjipanayis, George C. [Physics and Astronomy, University of Delaware (United States)

    2016-02-15

    In this paper, we explore the possibility of producing hexagonal Cobalt nanoparticles, with high saturation magnetization by direct chemical synthesis. The nanoparticles were synthesized by reduction of anhydrous cobalt (II) chloride by NaBH{sub 4} in tetraglyme at temperatures in the range of 200–270 °C under a nitrogen–hydrogen atmosphere. The reactions were done at high temperatures to allow for the formation of as-made hexagonal cobalt. The size of the particles was controlled by the addition of different surfactants. The best magnetic properties so far were obtained on spherical hexagonal Co nanoparticles with an average size of 45 nm, a saturation magnetization of 143 emu/g and coercivity of 500 Oe. the saturation magnetization and coercivity were further improved by annealing the Co nanoparticles leading to saturation magnetization of 160 emu/g and coercivity of 540 Oe. - Highlights: • We synthesized hexagonal cobalt nanoparticles by a new wet chemical method. • We considered the effects of different surfactants on particles magnetic properties. • The as-made Co nanoparticles had magnetic properties of 143 emu/g and 500 Oe. • After annealing magnetic properties of 160 emu/g and 540 Oe were obtained.

  17. National policy measures. Right approach to foreign direct investment flows

    Cătălin-Emilian HUIDUMAC-PETRESCU

    2013-02-01

    Full Text Available 2011 was a difficult year for all the countries, developed and emerging ones. For overcoming the negative effects of the financial crisis, many economies have established as purpose to adopt new economic policies regarding the foreign direct investment flows (FDI, even to stimulate the flows or to reduce it (protectionism measures. So, there can be identified two categories of national policies: measures for the FDI flows stimulation and measures whose aim was the weighting of FDI developing, through restriction and regulation. In the first category we could include the liberalization measures and promotional and faciletation policies. In this study we evidenced that the fundament of the second category of policies is the belief that the FDI outward lead to job exports, to a raise of unemployment and a weakness of the industrial base.Many reports on FDI flows, here we talk about those made by UNCTAD, show that the regulation and restriction policies are seen as a possible protectionism, especially in the agricultural and extractive industries, where there have been required nationalization processes and divestments. Even more, the economies which adopted this kind of policies have been less interested in investing abroad, the outward of FDI being affected and globally the total outward decreased.

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

    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.

  19. The Direct Anterior Approach Does Not Increase Return to Function Following Hemiarthroplasty for Femoral Neck Fracture.

    Carlson, Victor R; Ong, Alvin C; Orozco, Fabio R; Lutz, Rex W; Duque, Andres F; Post, Zachary D

    2017-11-01

    The purpose of this study was to evaluate functional outcomes for hemiarthroplasty using a direct anterior approach or a direct lateral approach for femoral neck fracture. This retrospective review used data collected from a single institution between 2006 and 2016. Eighty-five and 75 consecutive patients who underwent hemiarthroplasty via a direct anterior approach and a direct lateral approach, respectively, met inclusion criteria. All patients with femoral neck fractures were treated by 1 of 2 fellowship-trained orthopedic surgeons using the direct anterior approach or the direct lateral approach to hemiarthroplasty. Disposition, ambulation, and other perioperative surgical outcomes were compared between the cohorts. Compared with the direct lateral cohort, the direct anterior cohort had a shorter mean operative time (2.4 minutes, P<.01), a shorter mean length of hospital stay (2.7 days, P<.01), and a smaller mean decrease in hemoglobin postoperatively (0.7 g/dL, P<.01). No significant difference was observed between the cohorts for postoperative disposition, the number of feet ambulated on the second postoperative day, or the prevalence of ambulatory decline at 4- to 6-week and 4- to 6-month follow-up visits. Compared with the direct lateral approach, the direct anterior approach may benefit patients by small, but statistically significant, improvements in blood loss, surgical time, and length of hospital stay after hemiarthroplasty. However, the direct anterior approach does not appear to decrease the likelihood of transfer to a skilled nursing facility postoperatively or accelerate return to preoperative function. [Orthopedics. 2017; 40(6):e1055-e1061.]. Copyright 2017, SLACK Incorporated.

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

    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

  1. The evolution model of Uppsala in light of the complex adaptive systems approach

    Rennaly Alves da Silva

    2013-11-01

    Full Text Available The behavioral approach to the internationalization of companies explains that the movements toward external markets occur in accordance with the increasing commitment of resources to mitigate the effects of uncertainty and reduce the perception of risk. Evidence indicates that the theories and practices developed in the domestic market may not be able to explain the reality of companies that operate in international markets. Thus, the Paradigm of Complexity presents itself as a comprehensive alternative to realize the relationships within organizations and markets. Accordingly, the aim of this theoretical paper is to analyze the evolution of the Uppsala Model between years 1975 and 2010 with the understanding of the companies in the process of internationalization as Complex Adaptive Systems, in accordance with the Model Kelly and Allison (1998. Four propositions are presented that show the links between the approaches. The most surprising is the perception that the conceptual evolution of the Uppsala Model seems to accompany the evolution of complexity levels, presented in Model Kelly and Allison.

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

    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

  3. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    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

  4. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    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

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

    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.

  6. Evolution of the Theoretical Approaches to Disclosing the Economic Substance of Accumulation of Capital

    Yemets Vadym V.

    2016-05-01

    Full Text Available The article proposes a classification for periods of evolution of theoretical approaches to disclosing the economic substance of accumulation of capital, taking into account the civilizational approach to the development of society. The author has proposed five stages in the evolution of theoretical approaches, which are closely related to the development of economy and stipulate dominance of a certain form of accumulation of capital. So, the first stage (time period B.C. – the 5th Century is referred to as Individual-social significance of accumulation of capital; the second stage (from the 6th century to the 16th century – Accumulation of monetary capitals; the third stage (from the mid-17th century until the end of the 18th century – Industrialproduction accumulation of capital; the fourth stage (from the mid-19th century until the 70s of the 20th century – Investment-oriented accumulation of capital; the fifth stage (from the 70s of the 20th century up to the current period – Globally-intensive accumulation of capital.

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

    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.

  8. The geoforecasting approach and long-term prediction of evolutive nuclide migration

    Peaudecerf, P.; D'Alessandro, M.; Canceill, M.; Fourniquet, J.; Godefroy, P.

    1985-01-01

    Safety analysis of long-lived radioactive waste repositories is dependent on natural site evolution scenarios. This is a complex problem given that there may be a large number of interdependent factors whose occurrence probability is usually very difficult to quantify. A major methodological effort has therefore been undertaken in this field under the terms of the Community's R and D programme. Research teams from the JRC and the BRGM tackled the problems by way of two complementary approaches; A critical analysis of existing methods was also undertaken at the request of the Commission. This paper sets out to summarize the work and, as far as possible, make a methodological evaluation

  9. Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach

    Sujita Kumar Kar

    2015-01-01

    Full Text Available Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its "culture-bound" status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder.

  10. A Self-Adaptive Evolutionary Approach to the Evolution of Aesthetic Maps for a RTS Game

    Lara-Cabrera, Raúl; Cotta, Carlos; Fernández-Leiva, Antonio J.

    2014-01-01

    Procedural content generation (PCG) is a research eld on the rise,with numerous papers devoted to this topic. This paper presents a PCG method based on a self-adaptive evolution strategy for the automatic generation of maps for the real-time strategy (RTS) game PlanetWars. These maps are generated in order to ful ll the aesthetic preferences of the user, as implied by her assessment of a collection of maps used as training set. A topological approach is used for the characterization of th...

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

    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

  12. Quasi-Steady Evolution of Hillslopes in Layered Landscapes: An Analytic Approach

    Glade, R. C.; Anderson, R. S.

    2018-01-01

    Landscapes developed in layered sedimentary or igneous rocks are common on Earth, as well as on other planets. Features such as hogbacks, exposed dikes, escarpments, and mesas exhibit resistant rock layers adjoining more erodible rock in tilted, vertical, or horizontal orientations. Hillslopes developed in the erodible rock are typically characterized by steep, linear-to-concave slopes or "ramps" mantled with material derived from the resistant layers, often in the form of large blocks. Previous work on hogbacks has shown that feedbacks between weathering and transport of the blocks and underlying soft rock can create relief over time and lead to the development of concave-up slope profiles in the absence of rilling processes. Here we employ an analytic approach, informed by numerical modeling and field data, to describe the quasi-steady state behavior of such rocky hillslopes for the full spectrum of resistant layer dip angles. We begin with a simple geometric analysis that relates structural dip to erosion rates. We then explore the mechanisms by which our numerical model of hogback evolution self-organizes to meet these geometric expectations, including adjustment of soil depth, erosion rates, and block velocities along the ramp. Analytical solutions relate easily measurable field quantities such as ramp length, slope, block size, and resistant layer dip angle to local incision rate, block velocity, and block weathering rate. These equations provide a framework for exploring the evolution of layered landscapes and pinpoint the processes for which we require a more thorough understanding to predict their evolution over time.

  13. Effects of extrinsic mortality on the evolution of aging: a stochastic modeling approach.

    Maxim Nikolaievich Shokhirev

    Full Text Available The evolutionary theories of aging are useful for gaining insights into the complex mechanisms underlying senescence. Classical theories argue that high levels of extrinsic mortality should select for the evolution of shorter lifespans and earlier peak fertility. Non-classical theories, in contrast, posit that an increase in extrinsic mortality could select for the evolution of longer lifespans. Although numerous studies support the classical paradigm, recent data challenge classical predictions, finding that high extrinsic mortality can select for the evolution of longer lifespans. To further elucidate the role of extrinsic mortality in the evolution of aging, we implemented a stochastic, agent-based, computational model. We used a simulated annealing optimization approach to predict which model parameters predispose populations to evolve longer or shorter lifespans in response to increased levels of predation. We report that longer lifespans evolved in the presence of rising predation if the cost of mating is relatively high and if energy is available in excess. Conversely, we found that dramatically shorter lifespans evolved when mating costs were relatively low and food was relatively scarce. We also analyzed the effects of increased predation on various parameters related to density dependence and energy allocation. Longer and shorter lifespans were accompanied by increased and decreased investments of energy into somatic maintenance, respectively. Similarly, earlier and later maturation ages were accompanied by increased and decreased energetic investments into early fecundity, respectively. Higher predation significantly decreased the total population size, enlarged the shared resource pool, and redistributed energy reserves for mature individuals. These results both corroborate and refine classical predictions, demonstrating a population-level trade-off between longevity and fecundity and identifying conditions that produce both

  14. Materials for pressure equipment under the new approach directives: a one-year home-experience

    Zdankiewicz, M.

    2005-01-01

    The New Approach Directives concerning pressure equipment set forth basic safety requirements for their designing, manufacturing and testing. The said requirements are being implemented in the field of materials in Poland after one-year experience. (author)

  15. Directive Versus Participative Leadership: Two Complementary Approaches to Managing School Effectiveness

    Somech, Anit

    2005-01-01

    Purpose: The educational literature reflects the widely shared belief that participative leadership has an overwhelming advantage over the contrasting style of directive leadership in organizational and team effectiveness. The purpose of this study was to examine the relative effect of a directive leadership approach as compared with a…

  16. Direct evaluation of free energy for large system through structure integration approach.

    Takeuchi, Kazuhito; Tanaka, Ryohei; Yuge, Koretaka

    2015-09-30

    We propose a new approach, 'structure integration', enabling direct evaluation of configurational free energy for large systems. The present approach is based on the statistical information of lattice. Through first-principles-based simulation, we find that the present method evaluates configurational free energy accurately in disorder states above critical temperature.

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

    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

  18. Computational Experiment Approach to Controlled Evolution of Procurement Pattern in Cluster Supply Chain

    Xiao Xue

    2015-01-01

    Full Text Available Companies have been aware of the benefits of developing Cluster Supply Chains (CSCs, and they are spending a great deal of time and money attempting to develop the new business pattern. Yet, the traditional techniques for identifying CSCs have strong theoretical antecedents, but seem to have little traction in the field. We believe this is because the standard techniques fail to capture evolution over time, nor provide useful intervention measures to reach goals. To address these problems, we introduce an agent-based modeling approach to evaluate CSCs. Taking collaborative procurement as research object, our approach is composed of three parts: model construction, model instantiation, and computational experiment. We use the approach to explore the service charging policy problem in collaborative procurement. Three kinds of service charging polices are compared in the same experiment environment. Finally, “Fixed Cost” is identified as the optimal policy under the stable market environment. The case study can help us to understand the workflow of applying the approach, and provide valuable decision support applications to industry.

  19. Integrated management system - management standards evolution and the IAEA new approach

    Oliveira, Dirceu Paulo de; Zouain, Desiree Moraes

    2007-01-01

    The management standards application began in military and nuclear areas towards the end of Second World War, when some westerns countries developed quality standards to improve their means to assess suppliers' conditions to assure their products conformance, which was increasingly complex and required a higher degree of reliability. Afterwards, the quality standards application was extended to the consumer market focused on consumers' requirements satisfaction. Coming along the society crescent concern about quality of life, other management standards were developed, such as those dealing with environmental and sustainable development, occupational health and safety, social accountability and so on. As a consequence, the management process became complex. The management system integrated form approach makes possible the compatibility of distinct and complementary interests from several functions and disciplines involved and supply the absence of the organizations' holistic approach. According to this integrated management approach, the Agency - 'International Atomic Energy Agency' (IAEA) - decided to review the structure of the 50-C-Q standard - 'Quality Assurance for Safety in Nuclear Power Plants and Other Nuclear Installations', from 1996, publishing in 2006 the new GS-R-3 standard - 'The Management System for Facilities and Activities - Safety Requirements'. This work presents a brief evolution of management standards and integrated management approach, showing the Agency's new vision concerning this issue with the GS-R-3 standard publication. (author)

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  5. Trickle-down evolution: an approach to getting major evolutionary adaptive changes into textbooks and curricula.

    Padian, Kevin

    2008-08-01

    Although contemporary high school and college textbooks of biology generally cover the principles and data of microevolution (genetic and populational change) and speciation rather well, coverage of what is known of the major changes in evolution (macroevolution), and how the evidence is understood is generally poor to nonexistent. It is critical to improve this because acceptance of evolution by the American public rests on the understanding of how we know what we know about the emergence of major new taxonomic groups, and about their adaptations, behaviors, and ecologies in geologic time. An efficient approach to this problem is to improve the illustrations in college textbooks to show the consilience of different lines of fossil, morphological, and molecular evidence mapped on phylogenies. Such "evograms" will markedly improve traditional illustrations of phylogenies, "menageries," and "companatomies." If "evograms" are installed at the college level, the basic principles and evidence of macroevolution will be more likely taught in K-12, thus providing an essential missing piece in biological education.

  6. A POPULATION MEMETICS APPROACH TO CULTURAL EVOLUTION IN CHAFFINCH SONG: DIFFERENTIATION AMONG POPULATIONS.

    Lynch, Alejandro; Baker, Allan J

    1994-04-01

    We investigated cultural evolution in populations of common chaffinches (Fringilla coelebs) in the Atlantic islands (Azores, Madeira, and Canaries) and neighboring continental regions (Morocco and Iberia) by employing a population-memetic approach. To quantify differentiation, we used the concept of a song meme, defined as a single syllable or a series of linked syllables capable of being transmitted. The levels of cultural differentiation are higher among the Canaries populations than among the Azorean ones, even though the islands are on average closer to each other geographically. This is likely the result of reduced levels of migration, lower population sizes, and bottlenecks (possibly during the colonization of these populations) in the Canaries; all these factors produce a smaller effective population size and therefore accentuate the effects of differentiation by random drift. Significant levels of among-population differentiation in the Azores, in spite of substantial levels of migration, attest to the differentiating effects of high mutation rates of memes, which allow the accumulation of new mutants in different populations before migration can disperse them throughout the entire region. © 1994 The Society for the Study of Evolution.

  7. Biochemical approaches to C4 photosynthesis evolution studies: the case of malic enzymes decarboxylases.

    Saigo, Mariana; Tronconi, Marcos A; Gerrard Wheeler, Mariel C; Alvarez, Clarisa E; Drincovich, María F; Andreo, Carlos S

    2013-11-01

    C4 photosynthesis enables the capture of atmospheric CO2 and its concentration at the site of RuBisCO, thus counteracting the negative effects of low atmospheric levels of CO2 and high atmospheric levels of O2 (21 %) on photosynthesis. The evolution of this complex syndrome was a multistep process. It did not occur by simply recruiting pre-exiting components of the pathway from C3 ancestors which were already optimized for C4 function. Rather it involved modifications in the kinetics and regulatory properties of pre-existing isoforms of non-photosynthetic enzymes in C3 plants. Thus, biochemical studies aimed at elucidating the functional adaptations of these enzymes are central to the development of an integrative view of the C4 mechanism. In the present review, the most important biochemical approaches that we currently use to understand the evolution of the C4 isoforms of malic enzyme are summarized. It is expected that this information will help in the rational design of the best decarboxylation processes to provide CO2 for RuBisCO in engineering C3 species to perform C4 photosynthesis.

  8. Cultural transmission and the evolution of human behaviour: a general approach based on the Price equation.

    El Mouden, C; André, J-B; Morin, O; Nettle, D

    2014-02-01

    Transmitted culture can be viewed as an inheritance system somewhat independent of genes that is subject to processes of descent with modification in its own right. Although many authors have conceptualized cultural change as a Darwinian process, there is no generally agreed formal framework for defining key concepts such as natural selection, fitness, relatedness and altruism for the cultural case. Here, we present and explore such a framework using the Price equation. Assuming an isolated, independently measurable culturally transmitted trait, we show that cultural natural selection maximizes cultural fitness, a distinct quantity from genetic fitness, and also that cultural relatedness and cultural altruism are not reducible to or necessarily related to their genetic counterparts. We show that antagonistic coevolution will occur between genes and culture whenever cultural fitness is not perfectly aligned with genetic fitness, as genetic selection will shape psychological mechanisms to avoid susceptibility to cultural traits that bear a genetic fitness cost. We discuss the difficulties with conceptualizing cultural change using the framework of evolutionary theory, the degree to which cultural evolution is autonomous from genetic evolution, and the extent to which cultural change should be seen as a Darwinian process. We argue that the nonselection components of evolutionary change are much more important for culture than for genes, and that this and other important differences from the genetic case mean that different approaches and emphases are needed for cultural than genetic processes. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  9. A population memetics approach to cultural evolution in chaffinch song: meme diversity within populations.

    Lynch, A; Baker, A J

    1993-04-01

    We investigated cultural evolution in populations of common chaffinches (Fringilla coelebs) in the Atlantic islands (Azores, Madeira, Canaries) and neighboring continental regions (Morocco, Iberia) by employing a population memetics approach. To quantify variability within populations, we used the concept of a song meme, defined as a single syllable or a series of linked syllables capable of being transmitted. The frequency distribution of memes within populations generally fit a neutral model in which there is an equilibrium between mutation, migration, and drift, which suggests that memes are functionally equivalent. The diversity of memes of single syllables is significantly greater in the Azores compared to all other regions, consistent with higher population densities of chaffinches there. On the other hand, memes of two to five syllables have greater diversity in Atlantic island and Moroccan populations compared to their Iberian counterparts. This higher diversity emanates from a looser syntax and increased recombination in songs, presumably because of relaxed selection for distinctive songs in these peripheral and depauperate avifaunas. We urge comparative population memetic studies of other species of songbirds and predict that they will lead to a formulation of a general theory for the cultural evolution of bird song analogous to population genetics theory for biological traits.

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

    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

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

    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.

  12. AXM mutagenesis: an efficient means for the production of libraries for directed evolution of proteins.

    Holland, Erika G; Buhr, Diane L; Acca, Felicity E; Alderman, Dawn; Bovat, Kristin; Busygina, Valeria; Kay, Brian K; Weiner, Michael P; Kiss, Margaret M

    2013-08-30

    Affinity maturation is an important part of the recombinant antibody development process. There are several well-established approaches for generating libraries of mutated antibody genes for affinity maturation, but these approaches are generally too laborious or expensive to allow high-throughput, parallel processing of multiple antibodies. Here, we describe a scalable approach that enables the generation of libraries with greater than 10(8) clones from a single Escherichia coli transformation. In our method, a mutated DNA fragment is produced using PCR conditions that promote nucleotide misincorporation into newly synthesized DNA. In the PCR reaction, one of the primers contains at least three phosphorothioate linkages at its 5' end, and treatment of the PCR product with a 5' to 3' exonuclease is used to preferentially remove the strand synthesized with the non-modified primer, resulting in a single-stranded DNA fragment. This fragment then serves as a megaprimer to prime DNA synthesis on a uracilated, circular, single-stranded template in a Kunkel-like mutagenesis reaction that biases nucleotide base-changes between the megaprimer and uracilated DNA sequence in favor of the in vitro synthesized megaprimer. This method eliminates the inefficient subcloning steps that are normally required for the construction of affinity maturation libraries from randomly mutagenized antibody genes. Copyright © 2013. Published by Elsevier B.V.

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

    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.

  14. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach.

    Maitre, Nathalie L; Ballard, Roberta A; Ellenberg, Jonas H; Davis, Stephanie D; Greenberg, James M; Hamvas, Aaron; Pryhuber, Gloria S

    2015-05-01

    Bronchopulmonary dysplasia (BPD) is the most common respiratory consequence of premature birth and contributes to significant short- and long-term morbidity, mortality and resource utilization. Initially defined as a radiographic, clinical and histopathological entity, the chronic lung disease known as BPD has evolved as obstetrical and neonatal care have improved the survival of lower gestational age infants. Now, definitions based on the need for supplementary oxygen at 28 days and/or 36 weeks provide a useful reference point in the neonatal intensive-care unit (NICU), but are no longer based on histopathological findings, and are neither designed to predict longer term respiratory consequences nor to study the evolution of a multifactorial disease. The aims of this review are to critically examine the evolution of the diagnosis of BPD and the challenges inherent to current classifications. We found that the increasing use of respiratory support strategies that administer ambient air without supplementary oxygen confounds oxygen-based definitions of BPD. Furthermore, lack of reproducible, genetic, biochemical and physiological biomarkers limits the ability to identify an impending BPD for early intervention, quantify disease severity for standardized classification and approaches and reliably predict the long-term outcomes. More comprehensive, multidisciplinary approaches to overcome these challenges involve longitudinal observation of extremely preterm infants, not only those with BPD, using genetic, environmental, physiological and clinical data as well as large databases of patient samples. The Prematurity and Respiratory Outcomes Program (PROP) will provide such a framework to address these challenges through high-resolution characterization of both NICU and post-NICU discharge outcomes.

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

    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.

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

    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.

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

    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.

  18. Transjugular intrahepatic portosystemic shunt by direct transcaval approach: indications and anatomic foundation

    Chu Jianguo; Sun Xiaoli; Huang He; Xu Xiaoming; Pu Longsong; Lv Chunyan; Sun Peng; Yang Shuhui; Liu Shuying

    2004-01-01

    Objective: To investigate into the indications and related anatomic foundation of transjugular intrahepatic portosystemic shunt (TIPS) creation by direct transcaval approach in patients with portal hypertension cirrhosis suffering unusual anatomy between the hepatic veins and portal bifurcation; and to evaluate the security, feasibility and clinical significance. Methods: Direct transcaval approach TIPS were performed in 65 patients including active variceal bleeding (n=52), intractable ascites (n=12), and as a bridge to liver transplantation (n=1). Results: Technical and functional success were achieved in all patients. The success rate was 100% without related complications including the technique and primary patency rate is obvious higher than classical TIPS. Conclusion: In patients with unusual anatomy between the hepatic veins and portal bifurcation, and inaccessible or inadequate hepatic veins, transcaval TIPS creation is secure and feasible. The results suggest that the direct transcaval approach offering favorable primary patency because the shunt has a straight line in construction

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  4. A novel anisotropic inversion approach for magnetotelluric data from subsurfaces with orthogonal geoelectric strike directions

    Schmoldt, Jan-Philipp; Jones, Alan G.

    2013-12-01

    The key result of this study is the development of a novel inversion approach for cases of orthogonal, or close to orthogonal, geoelectric strike directions at different depth ranges, for example, crustal and mantle depths. Oblique geoelectric strike directions are a well-known issue in commonly employed isotropic 2-D inversion of MT data. Whereas recovery of upper (crustal) structures can, in most cases, be achieved in a straightforward manner, deriving lower (mantle) structures is more challenging with isotropic 2-D inversion in the case of an overlying region (crust) with different geoelectric strike direction. Thus, investigators may resort to computationally expensive and more limited 3-D inversion in order to derive the electric resistivity distribution at mantle depths. In the novel approaches presented in this paper, electric anisotropy is used to image 2-D structures in one depth range, whereas the other region is modelled with an isotropic 1-D or 2-D approach, as a result significantly reducing computational costs of the inversion in comparison with 3-D inversion. The 1- and 2-D versions of the novel approach were tested using a synthetic 3-D subsurface model with orthogonal strike directions at crust and mantle depths and their performance was compared to results of isotropic 2-D inversion. Structures at crustal depths were reasonably well recovered by all inversion approaches, whereas recovery of mantle structures varied significantly between the different approaches. Isotropic 2-D inversion models, despite decomposition of the electric impedance tensor and using a wide range of inversion parameters, exhibited severe artefacts thereby confirming the requirement of either an enhanced or a higher dimensionality inversion approach. With the anisotropic 1-D inversion approach, mantle structures of the synthetic model were recovered reasonably well with anisotropy values parallel to the mantle strike direction (in this study anisotropy was assigned to the

  5. A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

    Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.

    2011-01-01

    A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594

  6. Adaptive approach to global synchronization of directed networks with fast switching topologies

    Qin Buzhi; Lu Xinbiao

    2010-01-01

    Global synchronization of directed networks with switching topologies is investigated. It is found that if there exists at least one directed spanning tree in the network with the fixed time-average topology and the time-average topology is achieved sufficiently fast, the network will reach global synchronization for appreciate coupling strength. Furthermore, this appreciate coupling strength may be obtained by local adaptive approach. A sufficient condition about the global synchronization is given. Numerical simulations verify the effectiveness of the adaptive strategy.

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

    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).

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

    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.

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

    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.

  10. The evolution of strategic management research: Recent trends and current directions

    Luis Ángel Guerras-Martín

    2014-04-01

    Full Text Available Strategic management is a relatively youthful discipline that has steadily matured over the past fifty years. The field has become consolidated over this period, while simultaneously expanding the range of topics analyzed and research methodologies used. Different theories and approaches, addressing different research topics, have been developed to explain the reasons underlying firms’ competitive advantage and success. In this paper, we posit the existence of two pendulums in constant motion that, on the one hand, reflect the tension that has historically existed between the focus on internal firm factors and external environmental attributes respectively and, on the other hand, the tension between a more macro level of analysis, i.e., the firm and its environment, and a more micro level one, i.e., individuals and their relations within the firm. The frontier of research in strategic management is shaped by the simultaneous movement of both pendulums.

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

    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.

  12. Direct electron transfer: an approach for electrochemical biosensors with higher selectivity and sensitivity

    Freire Renato S.

    2003-01-01

    Full Text Available The most promising approach for the development of electrochemical biosensors is to establish a direct electrical communication between the biomolecules and the electrode surface. This review focuses on advances, directions and strategies in the development of third generation electrochemical biosensors. Subjects covered include a brief description of the fundamentals of the electron transfer phenomenon and amperometric biosensor development (different types and new oriented enzyme immobilization techniques. Special attention is given to different redox enzymes and proteins capable of electrocatalyzing reactions via direct electron transfer. The analytical applications and future trends for third generation biosensors are also presented and discussed.

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

    Jianhua Sui

    2008-11-01

    information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.

  14. Teaching and Learning Evolution: Testing the Principles of a Constructivist Approach through Action Research

    Oliver, Mary

    2011-01-01

    A tenth grade class in an international school studied evolution for four weeks as part of the study of Biology. A diagnostic test was used to determine the main misconceptions students have as they come to the study of evolution. This was followed by a series of explorations of different conceptual models to account for evolution, structured…

  15. Integrated approach for sinkhole evaluation and evolution prediction in the Central Ebro Basin (NE Spain

    Oscar Pueyo Anchuela

    2017-06-01

    Full Text Available Evaluation of karst hazards benefits from the integration of different techniques, methodologies and approaches. Each one presents a different signature and is sensitive to certain indicators related to karst hazards. In some cases, detailed analysis permits the evaluation of representativeness either from isolated approaches or by means of integrated analyses. In this study, we present the evaluation of an area with high density of karstic collapses at different evolutionary stages through the integration of surficial, historical, geomorphological and geophysical data in order to finally define the evolutionary model for karst activity development. The obtained dataset permits to identify different steps in sinkhole evolution: (i cavities and open sinkholes, (ii filling of these cavities, with materials having different signatures, (iii the progression from collapses to subsidence sinkholes and (iv enlargement through collapses in marginal areas of previous sinkholes. The presence of different stages of this evolutionary model permits to determine their own signatures that can be of application in contexts where analysis cannot be so systematic and also to evaluate the definition of the marginal areas of previous sinkholes as the most hazardous sectors.

  16. A mutualistic approach to morality: the evolution of fairness by partner choice.

    Baumard, Nicolas; André, Jean-Baptiste; Sperber, Dan

    2013-02-01

    What makes humans moral beings? This question can be understood either as a proximate “how” question or as an ultimate “why” question. The “how” question is about the mental and social mechanisms that produce moral judgments and interactions, and has been investigated by psychologists and social scientists. The “why” question is about the fitness consequences that explain why humans have morality, and has been discussed by evolutionary biologists in the context of the evolution of cooperation. Our goal here is to contribute to a fruitful articulation of such proximate and ultimate explanations of human morality. We develop an approach to morality as an adaptation to an environment in which individuals were in competition to be chosen and recruited in mutually advantageous cooperative interactions. In this environment, the best strategy is to treat others with impartiality and to share the costs and benefits of cooperation equally. Those who offer less than others will be left out of cooperation; conversely, those who offer more will be exploited by their partners. In line with this mutualistic approach, the study of a range of economic games involving property rights, collective actions, mutual help and punishment shows that participants’ distributions aim at sharing the costs and benefits of interactions in an impartial way. In particular, the distribution of resources is influenced by effort and talent, and the perception of each participant’s rights on the resources to be distributed.

  17. A quasispecies approach to the evolution of sexual replication in unicellular organisms.

    Tannenbaum, Emmanuel; Fontanari, José F

    2008-03-01

    This study develops a simplified model describing the evolutionary dynamics of a population composed of obligate sexually and asexually reproducing, unicellular organisms. The model assumes that the organisms have diploid genomes consisting of two chromosomes, and that the sexual organisms replicate by first dividing into haploid intermediates, which then combine with other haploids, followed by the normal mitotic division of the resulting diploid into two new daughter cells. We assume that the fitness landscape of the diploids is analogous to the single-fitness-peak approach often used in single-chromosome studies. That is, we assume a master chromosome that becomes defective with just one point mutation. The diploid fitness then depends on whether the genome has zero, one, or two copies of the master chromosome. We also assume that only pairs of haploids with a master chromosome are capable of combining so as to produce sexual diploid cells, and that this process is described by second-order kinetics. We find that, in a range of intermediate values of the replication fidelity, sexually reproducing cells can outcompete asexual ones, provided the initial abundance of sexual cells is above some threshold value. The range of values where sexual reproduction outcompetes asexual reproduction increases with decreasing replication rate and increasing population density. We critically evaluate a common approach, based on a group selection perspective, used to study the competition between populations and show its flaws in addressing the evolution of sex problem.

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

    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.

  19. Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach.

    Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M; El Fakhri, Georges

    2013-10-01

    Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%-29% and 32%-70% for 50 × 10(6) and 10 × 10(6) detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40-50 iterations), while more than 500 iterations were needed for CG. The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method.

  20. A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining

    den Uyl, T.E.; Gladwin, T.E.; Rinck, M.; Lindenmeyer, J.; Wiers, R.W.

    2017-01-01

    Two studies showed an improvement in clinical outcomes after alcohol approach bias retraining, a form of Cognitive Bias Modification (CBM). We investigated whether transcranial direct current stimulation (tDCS) could enhance effects of CBM. TDCS is a neuromodulation technique that can increase

  1. Seasonal and daily variation of directions of approach to ground and balloon stations

    Orozco, A.; Gall, R.

    1975-01-01

    The seasonal and daily variations of approach directions induced by the distortion of magnetic cavity has been studied by trajectory tracing technique in magnetospheric models. The main characteristics of these variations are reported here for McMurdo, Thule and Fort Churchill. (orig./WBU) [de

  2. Comparison between AGC and a tuningless LFC approach based on direct observation of DERs

    Prostejovsky, Alexander Maria; Marinelli, Mattia

    2017-01-01

    , and the resulting reduction of available inertia. In this paper, we propose a tuningless Load-Frequency Control (LFC) approach able to cope with the changing dynamics of electric power grids. Harnessing the possibilities of modern monitoring and communication means, the so-called Direct Load-Frequency Control (DLFC...

  3. Self-directed learning skills in air-traffic control training; An eye-tracking approach

    Van Meeuwen, Ludo; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen; Bock, Jeano; Kirschner, Paul A.

    2011-01-01

    Van Meeuwen, L. W., Brand-Gruwel, S., De Bock, J. J. P. R., Kirschner, P. A., & Van Merriënboer, J. J. G. (2010, September). Self-directed Learning Skills in Air-traffic Control Training; An Eye-tracking Approach. Paper presented at the European Association for Aviation Psychology, Budapest.

  4. Simulating mesoscale coastal evolution for decadal coastal management: A new framework integrating multiple, complementary modelling approaches

    van Maanen, Barend; Nicholls, Robert J.; French, Jon R.; Barkwith, Andrew; Bonaldo, Davide; Burningham, Helene; Brad Murray, A.; Payo, Andres; Sutherland, James; Thornhill, Gillian; Townend, Ian H.; van der Wegen, Mick; Walkden, Mike J. A.

    2016-03-01

    Coastal and shoreline management increasingly needs to consider morphological change occurring at decadal to centennial timescales, especially that related to climate change and sea-level rise. This requires the development of morphological models operating at a mesoscale, defined by time and length scales of the order 101 to 102 years and 101 to 102 km. So-called 'reduced complexity' models that represent critical processes at scales not much smaller than the primary scale of interest, and are regulated by capturing the critical feedbacks that govern landform behaviour, are proving effective as a means of exploring emergent coastal behaviour at a landscape scale. Such models tend to be computationally efficient and are thus easily applied within a probabilistic framework. At the same time, reductionist models, built upon a more detailed description of hydrodynamic and sediment transport processes, are capable of application at increasingly broad spatial and temporal scales. More qualitative modelling approaches are also emerging that can guide the development and deployment of quantitative models, and these can be supplemented by varied data-driven modelling approaches that can achieve new explanatory insights from observational datasets. Such disparate approaches have hitherto been pursued largely in isolation by mutually exclusive modelling communities. Brought together, they have the potential to facilitate a step change in our ability to simulate the evolution of coastal morphology at scales that are most relevant to managing erosion and flood risk. Here, we advocate and outline a new integrated modelling framework that deploys coupled mesoscale reduced complexity models, reductionist coastal area models, data-driven approaches, and qualitative conceptual models. Integration of these heterogeneous approaches gives rise to model compositions that can potentially resolve decadal- to centennial-scale behaviour of diverse coupled open coast, estuary and inner

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

    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

  6. A Simple Approach to Derive a Novel N-Soliton Solution for a (3+1)-Dimensional Nonlinear Evolution Equation

    Wu Jianping

    2010-01-01

    Based on the Hirota bilinear form, a simple approach without employing the standard perturbation technique, is presented for constructing a novel N-soliton solution for a (3+1)-dimensional nonlinear evolution equation. Moreover, the novel N-soliton solution is shown to have resonant behavior with the aid of Mathematica. (general)

  7. Valence evaluation with approaching or withdrawing cues: directly testing valence-arousal conflict theory.

    Wang, Yan Mei; Li, Ting; Li, Lin

    2017-07-19

    The valence-arousal conflict theory assumes that both valence and arousal will trigger approaching or withdrawing tendencies. It also predicts that the speed of processing emotional stimuli will depend on whether valence and arousal trigger conflicting or congruent motivational tendencies. However, most previous studies have provided evidence of the interaction between valence and arousal only, and have not provided direct proof of the interactive links between valence, arousal and motivational tendencies. The present study provides direct evidence for the relationship between approach-withdrawal tendencies and the valence-arousal conflict. In an empirical test, participants were instructed to judge the valence of emotional words after visual-spatial cues that appeared to be either approaching or withdrawing from participants. A three-way interaction (valence, arousal, and approach-withdrawal tendency) was observed such that the response time was shorter if participants responded to a negative high-arousal stimulus after a withdrawing cue, or to a positive low-arousal stimulus after an approaching cue. These findings suggest that the approach-withdrawal tendency indeed plays a crucial role in valence-arousal conflict, and that the effect depends on the congruency of valence, arousal and tendency at an early stage of processing.

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

    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.

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

    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.

  10. Time-dependent evolution of rock slopes by a multi-modelling approach

    Bozzano, F.; Della Seta, M.; Martino, S.

    2016-06-01

    This paper presents a multi-modelling approach that incorporates contributions from morpho-evolutionary modelling, detailed engineering-geological modelling and time-dependent stress-strain numerical modelling to analyse the rheological evolution of a river valley slope over approximately 102 kyr. The slope is located in a transient, tectonically active landscape in southwestern Tyrrhenian Calabria (Italy), where gravitational processes drive failures in rock slopes. Constraints on the valley profile development were provided by a morpho-evolutionary model based on the correlation of marine and river strath terraces. Rock mass classes were identified through geomechanical parameters that were derived from engineering-geological surveys and outputs of a multi-sensor slope monitoring system. The rock mass classes were associated to lithotechnical units to obtain a high-resolution engineering-geological model along a cross section of the valley. Time-dependent stress-strain numerical modelling reproduced the main morpho-evolutionary stages of the valley slopes. The findings demonstrate that a complex combination of eustatism, uplift and Mass Rock Creep (MRC) deformations can lead to first-time failures of rock slopes when unstable conditions are encountered up to the generation of stress-controlled shear zones. The multi-modelling approach enabled us to determine that such complex combinations may have been sufficient for the first-time failure of the S. Giovanni slope at approximately 140 ka (MIS 7), even without invoking any trigger. Conversely, further reactivations of the landslide must be related to triggers such as earthquakes, rainfall and anthropogenic activities. This failure involved a portion of the slope where a plasticity zone resulted from mass rock creep that evolved with a maximum strain rate of 40% per thousand years, after the formation of a river strath terrace. This study demonstrates that the multi-modelling approach presented herein is a useful

  11. Novel Approaches to Manipulating Bacterial Pathogen Biofilms: Whole-Systems Design Philosophy and Steering Microbial Evolution.

    Penn, Alexandra S

    2016-01-01

    Understanding and manipulating bacterial biofilms is crucial in medicine, ecology and agriculture and has potential applications in bioproduction, bioremediation and bioenergy. Biofilms often resist standard therapies and the need to develop new means of intervention provides an opportunity to fundamentally rethink our strategies. Conventional approaches to working with biological systems are, for the most part, "brute force", attempting to effect control in an input and effort intensive manner and are often insufficient when dealing with the inherent non-linearity and complexity of living systems. Biological systems, by their very nature, are dynamic, adaptive and resilient and require management tools that interact with dynamic processes rather than inert artefacts. I present an overview of a novel engineering philosophy which aims to exploit rather than fight those properties, and hence provide a more efficient and robust alternative. Based on a combination of evolutionary theory and whole-systems design, its essence is what I will call systems aikido; the basic principle of aikido being to interact with the momentum of an attacker and redirect it with minimal energy expenditure, using the opponent's energy rather than one's own. In more conventional terms, this translates to a philosophy of equilibrium engineering, manipulating systems' own self-organisation and evolution so that the evolutionarily or dynamically stable state corresponds to a function which we require. I illustrate these ideas with a description of a proposed manipulation of environmental conditions to alter the stability of co-operation in the context of Pseudomonas aeruginosa biofilm infection of the cystic fibrosis lung.

  12. A modified differential evolution approach for dynamic economic dispatch with valve-point effects

    Yuan Xiaohui; Wang Liang; Yuan Yanbin; Zhang Yongchuan; Cao Bo; Yang Bo

    2008-01-01

    Dynamic economic dispatch (DED) plays an important role in power system operation, which is a complicated non-linear constrained optimization problem. It has nonsmooth and nonconvex characteristic when generation unit valve-point effects are taken into account. This paper proposes a modified differential evolution approach (MDE) to solve DED problem with valve-point effects. In the proposed MDE method, feasibility-based selection comparison techniques and heuristic search rules are devised to handle constraints effectively. In contrast to the penalty function method, the constraints-handling method does not require penalty factors or any extra parameters and can guide the population to the feasible region quickly. Especially, it can be satisfied equality constraints of DED problem precisely. Moreover, the effects of two crucial parameters on the performance of the MDE for DED problem are studied as well. The feasibility and effectiveness of the proposed method is demonstrated for application example and the test results are compared with those of other methods reported in literature. It is shown that the proposed method is capable of yielding higher quality solutions

  13. Soil evolution in spruce forest ecosystems: role and influence of humus studied by morphological approach

    Chersich S

    2007-01-01

    Full Text Available In order to understand the role and the mutual influences of humus and soil in alpine spruce forest ecosystems we studied and classified 7 soil - humic profiles on the 4 main forestry dynamics: open canopy, regeneration, young stand, tree stage. We studied the role of humification process in the pedologic process involving soils and vegetations studing humic and soil horizons. Study sites are located at an altitude of 1740 m a.s.l near Pellizzano (TN, and facing to the North. The parent soil material is predominantly composed of morenic sediments, probably from Cevedale glacier lying on a substrate of tonalite from Presanella (Adamello Tertiary pluton. The soil temperature regime is frigid, while the moisture regime is udic. The characteristics observed in field were correlated with classical chemical and physical soil analyses (MIPAF 2000. In order to discriminate the dominant soil forming process, the soils were described and classified in each site according to the World Reference Base (FAO-ISRIC-ISSS 1998. Humus was described and classified using the morphological-genetic approach (Jabiol et al. 1995. The main humus forms are acid and they are for the greater part Dysmoder on PODZOLS. The main pedogenetic processes is the podzolization, locally there are also hydromorphic processes. We associate a definite humus form with a pedological process at a particular step of the forest evolution. We concluded thath the soil study for a correct pedological interpretation must take count of the characteristics of the humic epipedon.

  14. A New Fokker-Planck Approach for the Relaxation-driven Evolution of Galactic Nuclei

    Vasiliev, Eugene

    2017-10-01

    We present an approach for simulating the collisional evolution of spherical isotropic stellar systems based on the one-dimensional Fokker-Planck equation. A novel aspect is that we use the phase volume as the argument of the distribution function instead of the traditionally used energy, which facilitates the solution. The publicly available code PhaseFlow implements a high-accuracy finite-element method for the Fokker-Planck equation, and can handle multiple-component systems, optionally with the central black hole and taking into account loss-cone effects and star formation. We discuss the energy balance in the general setting, and in application to the Bahcall-Wolf cusp around a central black hole, for which we derive a perturbative solution. We stress that the cusp is not a steady-state structure, but rather evolves in amplitude while retaining an approximately ρ \\propto {r}-7/4 density profile. Finally, we apply the method to the nuclear star cluster of the milky Way, and illustrate a possible evolutionary scenario in which a two-component system of lighter main-sequence stars and stellar-mass black holes develops a Bahcall-Wolf cusp in the heavier component and a weaker ρ \\propto {r}-3/2 cusp in the lighter, visible component, over the period of several Gyr. The present-day density profile is consistent with the recently detected mild cusp inside the central parsec, and is weakly sensitive to initial conditions.

  15. Application of enhanced discrete differential evolution approach to unit commitment problem

    Yuan Xiaohui; Su Anjun; Nie Hao; Yuan Yanbin; Wang Liang

    2009-01-01

    This paper proposes a discrete binary differential evolution (DBDE) approach to solve the unit commitment problem (UCP). The proposed method is enhanced by priority list based on the unit characteristics and heuristic search strategies to handle constraints effectively. The implementation of the proposed method for UCP consists of three stages. Firstly, the DBDE based on priority list is applied for unit scheduling when neglecting the minimum up/down time constraints. Secondly, repairing strategies are used to handle the minimum up/down time constraints and decommit excess spinning reserve units. Finally, heuristic unit substitution search and gray zone modification algorithm are used to improve optimal solution further. Furthermore, the effects of two crucial parameters on performance of the DBDE for solving UCP are studied as well. To verify the advantages of the method, the proposed method is tested and compared to the other methods on the systems with the number of units in the range of 10-100. Numerical results demonstrate that the proposed method is superior to other methods reported in the literature.

  16. Estimates of future discharges of the river Rhine using two scenario methodologies: direct versus delta approach

    2007-01-01

    Full Text Available Simulations with a hydrological model for the river Rhine for the present (1960–1989 and a projected future (2070–2099 climate are discussed. The hydrological model (RhineFlow is driven by meteorological data from a 90-years (ensemble of three 30-years simulation with the HadRM3H regional climate model for both present-day and future climate (A2 emission scenario. Simulation of present-day discharges is realistic provided that (1 the HadRM3H temperature and precipitation are corrected for biases, and (2 the potential evapotranspiration is derived from temperature only. Different methods are used to simulate discharges for the future climate: one is based on the direct model output of the future climate run (direct approach, while the other is based on perturbation of the present-day HadRM3H time series (delta approach. Both methods predict a similar response in the mean annual discharge, an increase of 30% in winter and a decrease of 40% in summer. However, predictions of extreme flows differ significantly, with increases of 10% in flows with a return period of 100 years in the direct approach and approximately 30% in the delta approach. A bootstrap method is used to estimate the uncertainties related to the sample size (number of years simulated in predicting changes in extreme flows.

  17. Nonstationary porosity evolution in mixing zone in coastal carbonate aquifer using an alternative modeling approach.

    Laabidi, Ezzeddine; Bouhlila, Rachida

    2015-07-01

    In the last few decades, hydrogeochemical problems have benefited from the strong interest in numerical modeling. One of the most recognized hydrogeochemical problems is the dissolution of the calcite in the mixing zone below limestone coastal aquifer. In many works, this problem has been modeled using a coupling algorithm between a density-dependent flow model and a geochemical model. A related difficulty is that, because of the high nonlinearity of the coupled set of equations, high computational effort is needed. During calcite dissolution, an increase in permeability can be identified, which can induce an increase in the penetration of the seawater into the aquifer. The majority of the previous studies used a fully coupled reactive transport model in order to model such problem. Romanov and Dreybrodt (J Hydrol 329:661-673, 2006) have used an alternative approach to quantify the porosity evolution in mixing zone below coastal carbonate aquifer at steady state. This approach is based on the analytic solution presented by Phillips (1991) in his book Flow and Reactions in Permeable Rock, which shows that it is possible to decouple the complex set of equation. This equation is proportional to the square of the salinity gradient, which can be calculated using a density driven flow code and to the reaction rate that can be calculated using a geochemical code. In this work, this equation is used in nonstationary step-by-step regime. At each time step, the quantity of the dissolved calcite is quantified, the change of porosity is calculated, and the permeability is updated. The reaction rate, which is the second derivate of the calcium equilibrium concentration in the equation, is calculated using the PHREEQC code (Parkhurst and Apello 1999). This result is used in GEODENS (Bouhlila 1999; Bouhlila and Laabidi 2008) to calculate change of the porosity after calculating the salinity gradient. For the next time step, the same protocol is used but using the updated porosity

  18. Beyond the top of the volcano? A unified approach to electrocatalytic oxygen reduction and oxygen evolution

    Busch, M.; Halck, N. B.; Kramm, U. I.; Siehrostami, S.; Krtil, Petr; Rossmeisl, J.

    2016-01-01

    Roč. 29, NOV 2016 (2016), s. 126-135 ISSN 2211-2855 Institutional support: RVO:61388955 Keywords : hydrogen evolution * catalytic-activity * Electrocatalysis * Oxygen reduction * Oxygen evolution * Volcano * Density functional theory Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 12.343, year: 2016

  19. Nonlinear mechanics of thin-walled structures asymptotics, direct approach and numerical analysis

    Vetyukov, Yury

    2014-01-01

    This book presents a hybrid approach to the mechanics of thin bodies. Classical theories of rods, plates and shells with constrained shear are based on asymptotic splitting of the equations and boundary conditions of three-dimensional elasticity. The asymptotic solutions become accurate as the thickness decreases, and the three-dimensional fields of stresses and displacements can be determined. The analysis includes practically important effects of electromechanical coupling and material inhomogeneity. The extension to the geometrically nonlinear range uses the direct approach based on the principle of virtual work. Vibrations and buckling of pre-stressed structures are studied with the help of linearized incremental formulations, and direct tensor calculus rounds out the list of analytical techniques used throughout the book. A novel theory of thin-walled rods of open profile is subsequently developed from the models of rods and shells, and traditionally applied equations are proven to be asymptotically exa...

  20. Variational approach to direct and inverse problems of atmospheric pollution studies

    Penenko, Vladimir; Tsvetova, Elena; Penenko, Alexey

    2016-04-01

    We present the development of a variational approach for solving interrelated problems of atmospheric hydrodynamics and chemistry concerning air pollution transport and transformations. The proposed approach allows us to carry out complex studies of different-scale physical and chemical processes using the methods of direct and inverse modeling [1-3]. We formulate the problems of risk/vulnerability and uncertainty assessment, sensitivity studies, variational data assimilation procedures [4], etc. A computational technology of constructing consistent mathematical models and methods of their numerical implementation is based on the variational principle in the weak constraint formulation specifically designed to account for uncertainties in models and observations. Algorithms for direct and inverse modeling are designed with the use of global and local adjoint problems. Implementing the idea of adjoint integrating factors provides unconditionally monotone and stable discrete-analytic approximations for convection-diffusion-reaction problems [5,6]. The general framework is applied to the direct and inverse problems for the models of transport and transformation of pollutants in Siberian and Arctic regions. The work has been partially supported by the RFBR grant 14-01-00125 and RAS Presidium Program I.33P. References: 1. V. Penenko, A.Baklanov, E. Tsvetova and A. Mahura . Direct and inverse problems in a variational concept of environmental modeling //Pure and Applied Geoph.(2012) v.169: 447-465. 2. V. V. Penenko, E. A. Tsvetova, and A. V. Penenko Development of variational approach for direct and inverse problems of atmospheric hydrodynamics and chemistry, Izvestiya, Atmospheric and Oceanic Physics, 2015, Vol. 51, No. 3, p. 311-319, DOI: 10.1134/S0001433815030093. 3. V.V. Penenko, E.A. Tsvetova, A.V. Penenko. Methods based on the joint use of models and observational data in the framework of variational approach to forecasting weather and atmospheric composition

  1. An abstract approach to some spectral problems of direct sum differential operators

    Maksim S. Sokolov

    2003-07-01

    Full Text Available In this paper, we study the common spectral properties of abstract self-adjoint direct sum operators, considered in a direct sum Hilbert space. Applications of such operators arise in the modelling of processes of multi-particle quantum mechanics, quantum field theory and, specifically, in multi-interval boundary problems of differential equations. We show that a direct sum operator does not depend in a straightforward manner on the separate operators involved. That is, on having a set of self-adjoint operators giving a direct sum operator, we show how the spectral representation for this operator depends on the spectral representations for the individual operators (the coordinate operators involved in forming this sum operator. In particular it is shown that this problem is not immediately solved by taking a direct sum of the spectral properties of the coordinate operators. Primarily, these results are to be applied to operators generated by a multi-interval quasi-differential system studied, in the earlier works of Ashurov, Everitt, Gesztezy, Kirsch, Markus and Zettl. The abstract approach in this paper indicates the need for further development of spectral theory for direct sum differential operators.

  2. Competition between direct interaction and Kondo effect: Renormalization-group approach

    Allub, R.

    1988-03-01

    Via the Wilson renormalization-group approach, the effect of the competition between direct interaction (J L ) and Kondo coupling is studied, in the magnetic susceptibility of a model with two different magnetic impurities. For the ferromagnetic interaction (J L > 0) between the localized impurities, we find a magnetic ground state and a divergent susceptibility at low temperatures. For (J L < 0), two different Kondo temperatures and a non-magnetic ground state are distinguished. (author). 12 refs, 1 fig

  3. Flexible, Symmetry-Directed Approach To Assembling Protein Cages (Publisher’s Version Open Access)

    2016-08-01

    construction of enzyme nanoreactors, encapsulation of protein cargos, targeted drug delivery , and polyvalent display of epitopes, where atomic-level precision...Flexible, symmetry-directed approach to assembling protein cages Aaron Sciorea, Min Sub, Philipp Koldeweyc, Joseph D. Eschweilera, Kelsey A. Diffleya...approved June 10, 2016 (received for review April 15, 2016) The assembly of individual protein subunits into large-scale symmet- rical structures is

  4. Mass Media as Actor in Political Process: Evolution of the Western Approaches since the 1950s. (Part 1)

    Гуторов, Владимир Александрович

    2013-01-01

    The author analyses evolution of western political science’s approaches to mass media and mass media’s role in political process in liberal democracies. The author focuses on theories of “Minimal Effect,” “Mediocracy,” “Effects Research,” “Tеxt Analysis,” “Use and Gratification Approach.” The author discusses A. Giddens’s structuration theory as the most elaborate approach to interpreting the role of mass media in the western political and social science.Key words: mass and political communic...

  5. LIFETIME AND SPECTRAL EVOLUTION OF A MAGMA OCEAN WITH A STEAM ATMOSPHERE: ITS DETECTABILITY BY FUTURE DIRECT IMAGING

    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.

  6. Directed Evolution of Recombinant C-Terminal Truncated Staphylococcus epidermidis Lipase AT2 for the Enhancement of Thermostability

    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.

  7. Three dimensional modelling of grain boundary interaction and evolution during directional solidification of multi-crystalline silicon

    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.

  8. MoS2 nanosheets direct supported on reduced graphene oxide: An advanced electrocatalyst for hydrogen evolution reaction.

    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.

  9. Directed evolution of toluene dioxygenase from Pseudomonas putida for improved selectivity toward cis-indandiol during indene bioconversion.

    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.

  10. A Direct Adaptive Control Approach in the Presence of Model Mismatch

    Joshi, Suresh M.; Tao, Gang; Khong, Thuan

    2009-01-01

    This paper considers the problem of direct model reference adaptive control when the plant-model matching conditions are violated due to abnormal changes in the plant or incorrect knowledge of the plant's mathematical structure. The approach consists of direct adaptation of state feedback gains for state tracking, and simultaneous estimation of the plant-model mismatch. Because of the mismatch, the plant can no longer track the state of the original reference model, but may be able to track a new reference model that still provides satisfactory performance. The reference model is updated if the estimated plant-model mismatch exceeds a bound that is determined via robust stability and/or performance criteria. The resulting controller is a hybrid direct-indirect adaptive controller that offers asymptotic state tracking in the presence of plant-model mismatch as well as parameter deviations.

  11. Directional approach to spatial structure of solutions to the Navier–Stokes equations in the plane

    Konieczny, P; Mucha, P B

    2011-01-01

    We investigate a steady flow of incompressible fluid in the plane. The motion is governed by the Navier–Stokes equations with prescribed velocity u ∞ at infinity. The main result shows the existence of unique solutions for arbitrary force, provided sufficient largeness of u ∞ . Furthermore a spatial structure of the solution is obtained in comparison with the Oseen flow. A key element of our new approach is based on a setting which treats the direction of the flow as the time direction. The analysis is done in the framework of the Fourier transform taken in one (perpendicular) direction and a special choice of function spaces which take into account the inhomogeneous character of the symbol of the Oseen system. From that point of view our technique can be used as an effective tool in examining spatial asymptotics of solutions to other systems modelled by elliptic equations

  12. Modern comprehensive approach to monitor the morphodynamic evolution of a restored river corridor

    N. Pasquale

    2011-04-01

    Full Text Available River restoration has become a common measure to repair anthropogenically-induced alteration of fluvial ecosystems. The inherent complexity of ecohydrologic systems leads to limitations in understanding the response of such systems to restoration over time. Therefore, a significant effort has been dedicated in the recent years worldwide to document the efficiency of restoration actions and to produce new effective guidelines that may help overcoming existing deficiencies. At the same time little attention was paid to illustrate the reasons and the use of certain monitoring and experimental techniques in spite of others, or in relation to the specific ecohydrologic process being investigated. The purpose of this paper is to enrich efforts in this direction by presenting the framework of experimental activities and the related experimental setup that we designed and installed in order to accomplish some of the research tasks of the multidisciplinary scientific project RECORD (Restored Corridor Dynamics. Therein, we studied the morphodynamic evolution of the restored reach of the River Thur near Niederneunforn (Switzerland, also in relation to the role of pioneer vegetation roots in stabilizing the alluvial sediment. In this work we describe the methodology chosen for monitoring the river morphodynamics, the dynamics of riparian and of in-bed vegetation and their mutual interactions, as well as the need of complementing such observations with experiments and with the hydraulic modeling of the site. We also discuss how the designed installation and the experiments integrate with the needs of other research groups within the project, in particular providing data for a number of investigations thereby including surface water and groundwater interactions, soil moisture and vegetation dynamics.

  13. Direct lateral approach to lumbar fusion is a biomechanically equivalent alternative to the anterior approach: an in vitro study.

    Laws, Cory J; Coughlin, Dezba G; Lotz, Jeffrey C; Serhan, Hassan A; Hu, Serena S

    2012-05-01

    A human cadaveric biomechanical study of lumbar mobility before and after fusion and with or without supplemental instrumentation for 5 instrumentation configurations. To determine the biomechanical differences between anterior lumbar interbody fusion (ALIF) and direct lateral interbody fusion (DLIF) with and without supplementary instrumentation. Some prior studies have compared various surgical approaches using the same interbody device whereas others have investigated the stabilizing effect of supplemental instrumentation. No published studies have performed a side-by-side comparison of standard and minimally invasive techniques with and without supplemental instrumentation. Eight human lumbosacral specimens (16 motion segments) were tested in each of the 5 following configurations: (1) intact, (2) with ALIF or DLIF cage, (3) with cage plus stabilizing plate, (4) with cage plus unilateral pedicle screw fixation (PSF), and (5) with cage plus bilateral PSF. Pure moments were applied to induce specimen flexion, extension, lateral bending, and axial rotation. Three-dimensional kinematic responses were measured and used to calculate range of motion, stiffness, and neutral zone. Compared to the intact state, DLIF significantly reduced range of motion in flexion, extension, and lateral bending (P = 0.0117, P = 0.0015, P = 0.0031). Supplemental instrumentation significantly increased fused-specimen stiffness for both DLIF and ALIF groups. For the ALIF group, bilateral PSF increased stiffness relative to stand-alone cage by 455% in flexion and 317% in lateral bending (P = 0.0009 and P < 0.0001). The plate increased ALIF group stiffness by 211% in extension and 256% in axial rotation (P = 0.0467 and P = 0.0303). For the DLIF group, bilateral PSF increased stiffness by 350% in flexion and 222% in extension (P < 0.0001 and P = 0.0008). No differences were observed between ALIF and DLIF groups supplemented with bilateral PSF. Our data support that the direct lateral approach

  14. Strongly and weakly directed approaches to teaching multiple representation use in physics

    Patrick B. Kohl

    2007-06-01

    Full Text Available Good use of multiple representations is considered key to learning physics, and so there is considerable motivation both to learn how students use multiple representations when solving problems and to learn how best to teach problem solving using multiple representations. In this study of two large-lecture algebra-based physics courses at the University of Colorado (CU and Rutgers, the State University of New Jersey, we address both issues. Students in each of the two courses solved five common electrostatics problems of varying difficulty, and we examine their solutions to clarify the relationship between multiple representation use and performance on problems involving free-body diagrams. We also compare our data across the courses, since the two physics-education-research-based courses take substantially different approaches to teaching the use of multiple representations. The course at Rutgers takes a strongly directed approach, emphasizing specific heuristics and problem-solving strategies. The course at CU takes a weakly directed approach, modeling good problem solving without teaching a specific strategy. We find that, in both courses, students make extensive use of multiple representations, and that this use (when both complete and correct is associated with significantly increased performance. Some minor differences in representation use exist, and are consistent with the types of instruction given. Most significant are the strong and broad similarities in the results, suggesting that either instructional approach or a combination thereof can be useful for helping students learn to use multiple representations for problem solving and concept development.

  15. Estimation of direction of arrival of a moving target using subspace based approaches

    Ghosh, Ripul; Das, Utpal; Akula, Aparna; Kumar, Satish; Sardana, H. K.

    2016-05-01

    In this work, array processing techniques based on subspace decomposition of signal have been evaluated for estimation of direction of arrival of moving targets using acoustic signatures. Three subspace based approaches - Incoherent Wideband Multiple Signal Classification (IWM), Least Square-Estimation of Signal Parameters via Rotation Invariance Techniques (LS-ESPRIT) and Total Least Square- ESPIRIT (TLS-ESPRIT) are considered. Their performance is compared with conventional time delay estimation (TDE) approaches such as Generalized Cross Correlation (GCC) and Average Square Difference Function (ASDF). Performance evaluation has been conducted on experimentally generated data consisting of acoustic signatures of four different types of civilian vehicles moving in defined geometrical trajectories. Mean absolute error and standard deviation of the DOA estimates w.r.t. ground truth are used as performance evaluation metrics. Lower statistical values of mean error confirm the superiority of subspace based approaches over TDE based techniques. Amongst the compared methods, LS-ESPRIT indicated better performance.

  16. A Bayesian approach to the evolution of metabolic networks on a phylogeny.

    Aziz Mithani

    2010-08-01

    Full Text Available The availability of genomes of many closely related bacteria with diverse metabolic capabilities offers the possibility of tracing metabolic evolution on a phylogeny relating the genomes to understand the evolutionary processes and constraints that affect the evolution of metabolic networks. Using simple (independent loss/gain of reactions or complex (incorporating dependencies among reactions stochastic models of metabolic evolution, it is possible to study how metabolic networks evolve over time. Here, we describe a model that takes the reaction neighborhood into account when modeling metabolic evolution. The model also allows estimation of the strength of the neighborhood effect during the course of evolution. We present Gibbs samplers for sampling networks at the internal node of a phylogeny and for estimating the parameters of evolution over a phylogeny without exploring the whole search space by iteratively sampling from the conditional distributions of the internal networks and parameters. The samplers are used to estimate the parameters of evolution of metabolic networks of bacteria in the genus Pseudomonas and to infer the metabolic networks of the ancestral pseudomonads. The results suggest that pathway maps that are conserved across the Pseudomonas phylogeny have a stronger neighborhood structure than those which have a variable distribution of reactions across the phylogeny, and that some Pseudomonas lineages are going through genome reduction resulting in the loss of a number of reactions from their metabolic networks.

  17. A general nonlinear evolution equation for irreversible conservative approach to stable equilibrium

    Beretta, G.P.

    1986-01-01

    This paper addresses a mathematical problem relevant to the question of nonequilibrium and irreversibility, namely, that of ''designing'' a general evolution equation capable of describing irreversible but conservative relaxtion towards equilibrium. The objective is to present an interesting mathematical solution to this design problem, namely, a new nonlinear evolution equation that satisfies a set of very stringent relevant requirements. Three different frameworks are defined from which the new equation could be adopted, with entirely different interpretations. Some useful well-known mathematics involving Gram determinants are presented and a nonlinear evolution equation is given which meets the stringent design specifications

  18. DNA DSB measurements and modelling approaches based on gamma-H2AX foci time evolution

    Esposito, Giuseppe; Campa, Alessandro; Antonelli, Francesca; Mariotti, Luca; Belli, Mauro; Giardullo, Paola; Simone, Giustina; Antonella Tabocchini, Maria; Ottolenghi, Andrea

    DNA double strand breaks (DSBs) induced by ionising radiation are considered the main dam-age related to the deleterious consequences in the cells. Unrepaired or mis-repaired DSBs can cause mutations or loss of chromosome regions which can eventually lead to cell death or neo-plastic transformation. Quantification of the number and complexity of DSBs induced by low doses of radiation remains a complex problem. About ten years ago Rogakou et al. proposed an immunofluorescent technique able to detect even a single DSB per cell. This approach is based on the serine 139 phosphorylation of many molecules (up to 2000) of histone H2AX (γg-H2AX) following the induction of a DSB in the DNA. DSB can be visualized as foci by immunofluores-cence by using phospho-specific antibodies, so that enumeration of foci can be used to measure DSB induction and processing. It is still not completely clear how γ-H2AX dephosphorylation takes place; however it has been related with DSB repair, in particular with the efficiency of DSB repair. In this work we analyse the H2AX phosphorylation-dephosphorylation kinetics after irradiation of primary human fibroblasts (AG1522 cell line) with radiation of differing quality, that is γ-rays and α-particles (125 keV/µm), with the aim of comparing the time evolution of γ-H2AX foci. Our results show that, after a dose of 0.5 Gy, both γ-rays and α-particles induce the maximum number of γ-H2AX foci within 30 minutes from irradiation, that this number depends on the radiation type and is consistent with the number of track traversal in α-irradiated nuclei, that the dephosphorylation kinetics are very different, being the α-induced foci rate of disappearence slower than that of γ-induced foci. In this work a modellistic approach to estimate the number of DSB induced by γ-rays detectable by using the γ-H2AX assay is presented. The competing processes of appearance and disappearance of visible foci will be modeled taking into account the

  19. Direct collapse to supermassive black hole seeds: comparing the AMR and SPH approaches.

    Luo, Yang; Nagamine, Kentaro; Shlosman, Isaac

    2016-07-01

    We provide detailed comparison between the adaptive mesh refinement (AMR) code enzo-2.4 and the smoothed particle hydrodynamics (SPH)/ N -body code gadget-3 in the context of isolated or cosmological direct baryonic collapse within dark matter (DM) haloes to form supermassive black holes. Gas flow is examined by following evolution of basic parameters of accretion flows. Both codes show an overall agreement in the general features of the collapse; however, many subtle differences exist. For isolated models, the codes increase their spatial and mass resolutions at different pace, which leads to substantially earlier collapse in SPH than in AMR cases due to higher gravitational resolution in gadget-3. In cosmological runs, the AMR develops a slightly higher baryonic resolution than SPH during halo growth via cold accretion permeated by mergers. Still, both codes agree in the build-up of DM and baryonic structures. However, with the onset of collapse, this difference in mass and spatial resolution is amplified, so evolution of SPH models begins to lag behind. Such a delay can have effect on formation/destruction rate of H 2 due to UV background, and on basic properties of host haloes. Finally, isolated non-cosmological models in spinning haloes, with spin parameter λ ∼ 0.01-0.07, show delayed collapse for greater λ, but pace of this increase is faster for AMR. Within our simulation set-up, gadget-3 requires significantly larger computational resources than enzo-2.4 during collapse, and needs similar resources, during the pre-collapse, cosmological structure formation phase. Yet it benefits from substantially higher gravitational force and hydrodynamic resolutions, except at the end of collapse.

  20. Critical Omissions and New Directions for Sustainable Tourism: A Situated Macro–Micro Approach

    Blanca A. Camargo

    2013-10-01

    Full Text Available This paper traces the history and evolution of sustainable tourism and identifies some critical issues and omissions in this and related approaches such as responsible tourism, ecotourism and pro-poor tourism. The academic, institutional and practical intersections of sustainable tourism and responsible tourism are examined. It reveals that important theoretical and practical considerations around well-being, inclusion, and sustainability have been omitted. A critical look at ecotourism reveals additional concerns, such as a cornucopia of guidelines and principles, without clear ethical justifications to support them. At the same time, academics in this domain have been slow to consider the modernist and neoliberal influences shaping ecotourism and sustainable tourism development, such as through the discourse of ecological modernization. We identify some key omissions, such as the missing ‘body’ in sustainable tourism discourse, lack of critical analysis of postcolonial and dependency issues, and propose re-situating ‘sustainable tourism’ within a micro–macro, local-global systems approach informed by a clear framework of justice and ethics.

  1. How Can a Multimodal Approach to Primate Communication Help Us Understand the Evolution of Communication?

    Bridget M. Waller; Katja Liebal; Anne M. Burrows; Katie. E. Slocombe

    2013-01-01

    Scientists studying the communication of non-human animals are often aiming to better understand the evolution of human communication, including human language. Some scientists take a phylogenetic perspective, where the goal is to trace the evolutionary history of communicative traits, while others take a functional perspective, where the goal is to understand the selection pressures underpinning specific traits. Both perspectives are necessary to fully understand the evolution of communicati...

  2. Patterns of technological innovation and evolution in the energy sector: A patent-based approach

    Lee, Kyungpyo; Lee, Sungjoo

    2013-01-01

    Given the ever-increasing pace and complexity of technological innovation in the energy sector, monitoring technological changes has become of strategic importance. One of the most common techniques for technology monitoring is patent analysis, which enables the identification of technological trends over time. However, few previous studies have carried out patent analysis in the energy sector. This study aims to explore patterns of innovation and of evolution in energy technologies, particularly focusing on similarities and differences across technologies. For this purpose, we first defined the relevant energy technologies and extracted the associated patent data from the United States Patents and Trademark Office (USPTO) and then adopted six patent indices and developed six patent maps to analyze their innovation characteristics. We then clustered energy technologies with similar characteristics, so defining innovation categories, and analyzed the changes in these characteristics over time to define their evolution categories. As one of the few attempts to investigate the overall trends in the energy sector's innovation and evolution, this study is expected to help develop an in-depth understanding of the energy industry, which will be useful in establishing technology strategies and policy in this rapidly changing sector. - Highlights: • We examined the patterns of innovation and evolution of energy technologies. • Six types of innovation patterns such as “competitive” or “mature” were identified. • Six types of evolution patterns such as “towards closed innovation” were identified. • The patterns of evolution were related to the patterns of innovation

  3. Ion Diffusion-Directed Assembly Approach to Ultrafast Coating of Graphene Oxide Thick Multilayers.

    Zhao, Xiaoli; Gao, Weiwei; Yao, Weiquan; Jiang, Yanqiu; Xu, Zhen; Gao, Chao

    2017-10-24

    The layer-by-layer (LbL) assembly approach has been widely used to fabricate multilayer coatings on substrates with multiple cycles, whereas it is hard to access thick films efficiently. Here, we developed an ion diffusion-directed assembly (IDDA) strategy to rapidly make multilayer thick coatings in one step on arbitrary substrates. To achieve multifunctional coatings, graphene oxide (GO) and metallic ions were selected as the typical building blocks and diffusion director in IDDA, respectively. With diffusion of metallic ions from substrate to negatively charged GO dispersion spontaneously (i.e., from high-concentration region to low-concentration region), GO was assembled onto the substrate sheet-by-sheet via sol-gel transformation. Because metallic ions with size of subnanometers can diffuse directionally and freely in the aqueous dispersion, GO was coated on the substrate efficiently, giving rise to films with desired thickness up to 10 μm per cycle. The IDDA approach shows three main merits: (1) high efficiency with a μm-scale coating rate; (2) controllability over thickness and evenness; and (3) generality for substrates of plastics, metals and ceramics with any shapes and morphologies. With these merits, IDDA strategy was utilized in the efficient fabrication of functional graphene coatings that exhibit outstanding performance as supercapacitors, electromagnetic interference shielding textiles, and anticorrosion coatings. This IDDA approach can be extended to other building blocks including polymers and colloidal nanoparticles, promising for the scalable production and application of multifunctional coatings.

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

    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.

  5. A phenomenological approach to simulating the evolution of radioactive-waste container damage due to pitting corrosion

    Henshall, G.A.

    1995-01-01

    The damage to high-level radioactive-waste containers by pitting corrosion is an important design and performance assessment consideration. It is desirable to calculate the evolution of the pit depth distribution, not just the time required for initial penetration of the containers, so that the area available for advective of diffusive release of radionuclides through the container can be estimated. A phenomenological approach for computing the time evolution of these distributions is presented which combines elements of the deterministic and stochastic aspects of pit growth. The consistency of this approach with the mechanisms believed to control the evolution of the pit depth distribution is discussed. Qualitative comparisons of preliminary model predictions with a variety of experimental data from the literature are shown to be generally favorable. The sensitivity of the simulated distributions to changes in the input parameters is discussed. Finally, the results of the current model are compared to those of existing approaches based on extreme-value statistics, particularly regarding the extrapolation of laboratory data to large exposed surface areas

  6. On Directed Edge-Disjoint Spanning Trees in Product Networks, An Algorithmic Approach

    A.R. Touzene

    2014-12-01

    Full Text Available In (Ku et al. 2003, the authors have proposed a construction of edge-disjoint spanning trees EDSTs in undirected product networks. Their construction method focuses more on showing the existence of a maximum number (n1+n2-1 of EDSTs in product network of two graphs, where factor graphs have respectively n1 and n2 EDSTs. In this paper, we propose a new systematic and algorithmic approach to construct (n1+n2 directed routed EDST in the product networks. The direction of an edge is added to support bidirectional links in interconnection networks. Our EDSTs can be used straightforward to develop efficient collective communication algorithms for both models store-and-forward and wormhole.

  7. Distributed Cooperative Optimal Control for Multiagent Systems on Directed Graphs: An Inverse Optimal Approach.

    Zhang, Huaguang; Feng, Tao; Yang, Guang-Hong; Liang, Hongjing

    2015-07-01

    In this paper, the inverse optimal approach is employed to design distributed consensus protocols that guarantee consensus and global optimality with respect to some quadratic performance indexes for identical linear systems on a directed graph. The inverse optimal theory is developed by introducing the notion of partial stability. As a result, the necessary and sufficient conditions for inverse optimality are proposed. By means of the developed inverse optimal theory, the necessary and sufficient conditions are established for globally optimal cooperative control problems on directed graphs. Basic optimal cooperative design procedures are given based on asymptotic properties of the resulting optimal distributed consensus protocols, and the multiagent systems can reach desired consensus performance (convergence rate and damping rate) asymptotically. Finally, two examples are given to illustrate the effectiveness of the proposed methods.

  8. Directional synthetic aperture flow imaging using a dual stage beamformer approach

    Li, Ye; Jensen, Jørgen Arendt

    2011-01-01

    . The new method has been studied using the Field II simulations and experimental flow rig measurements. A linear array transducer with 7 MHz center frequency is used, and 64 elements are active to transmit and receive signals. The data is processed in two stages. The first stage has a fixed focus point......A new method for directional synthetic aperture flow imaging using a dual stage beamformer approach is presented. The velocity estimation is angle independent and the amount of calculations is reduced compared to full synthetic aperture, but still maintains all the advantages at the same time....... In the second stage, focal points are considered as virtual sources and data is beamformed along the flow direction. Then the velocities are estimated by finding the spatial shift between two signals. In the experimental measurements the angle between the transmit beam and flow vessel was 70 and a laminar flow...

  9. Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

    Kim, Ye-Ram; Yang, Chul-Su

    2017-09-28

    Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

  10. Extension of the direct statistical approach to a volume parameter model (non-integer splitting)

    Burn, K.W.

    1990-01-01

    The Direct Statistical Approach is a rigorous mathematical derivation of the second moment for surface splitting and Russian Roulette games attached to the Monte Carlo modelling of fixed source particle transport. It has been extended to a volume parameter model (involving non-integer ''expected value'' splitting), and then to a cell model. The cell model gives second moment and time functions that have a closed form. This suggests the possibility of two different methods of solution of the optimum splitting/Russian Roulette parameters. (author)

  11. A hit and run approach to inducible direct reprogramming of astrocytes to neural stem cells

    Maria ePoulou

    2016-04-01

    Full Text Available Temporal and spatial control of gene expression can be achieved using an inducible system as a fundamental tool for regulated transcription in basic, applied and eventually in clinical research. We describe a novel hit and run inducible direct reprogramming approach. In a single step, two days post-transfection, transiently transfected Sox2FLAG under the Leu3p-αIPM inducible control (iSox2 triggers the activation of endogenous Sox2, redirecting primary astrocytes into abundant distinct nestin-positive radial glia cells. This technique introduces a unique novel tool for safe, rapid and efficient reprogramming amendable to regenerative medicine.

  12. Three-dimensional lagrangian approach to the classical relativistic dynamics of directly interacting particles

    Gaida, R.P.; Kluchkousky, Ya.B.; Tretyak, V.I.

    1987-01-01

    In the present report the main attention is paid to the interrelations of various three-dimensional approaches and to the relation of the latter to the Fokker-type action formalism; the problem of the correspondence between three-dimensional descriptions and singular Lagrangian formalism will be shortly concerned. The authors start with the three-dimensional Lagrangian formulation of the classical RDIT. The generality of this formalism enables, similarly as in the non-relativistic case, to consider it as a central link explaining naturally a number of features of other three-dimensional approaches, namely Newtonian (based directly on second order equations of motion) and Hamiltonian ones). It is also capable of describing four-dimensional manifestly covariant models using Fokker action integrals and singular Lagrangians

  13. Laparoscopic vs. open approach for colorectal cancer: evolution over time of minimal invasive surgery.

    Biondi, Antonio; Grosso, Giuseppe; Mistretta, Antonio; Marventano, Stefano; Toscano, Chiara; Drago, Filippo; Gangi, Santi; Basile, Francesco

    2013-01-01

    In the late '80s the successes of the laparoscopic surgery for gallbladder disease laid the foundations on the modern use of this surgical technique in a variety of diseases. In the last 20 years, laparoscopic colorectal surgery had become a popular treatment option for colorectal cancer patients. Many studies emphasized on the benefits stating the significant advantages of the laparoscopic approach compared with the open surgery of reduced blood loss, early return of intestinal motility, lower overall morbidity, and shorter duration of hospital stay, leading to a general agreement on laparoscopic surgery as an alternative to conventional open surgery for colon cancer. The reduced hospital stay may also decrease the cost of the laparoscopic surgery for colorectal cancer, despite th higher operative spending compared with open surgery. The average reduction in total direct costs is difficult to define due to the increasing cost over time, making challenging the comparisons between studies conducted during a time range of more than 10 years. However, despite the theoretical advantages of laparoscopic surgery, it is still not considered the standard treatment for colorectal cancer patients due to technical limitations or the characteristics of the patients that may affect short and long term outcomes. The laparoscopic approach to colectomy is slowly gaining acceptance for the management of colorectal pathology. Laparoscopic surgery for colon cancer demonstrates better short-term outcome, oncologic safety, and equivalent long-term outcome of open surgery. For rectal cancer, laparoscopic technique can be more complex depending on the tumor location. The advantages of minimally invasive surgery may translate better care quality for oncological patients and lead to increased cost saving through the introduction of active enhanced recovery programs which are likely cost-effective from the perspective of the hospital health-care providers.

  14. Factors that affect micro-tooling features created by direct printing approach

    Kumbhani, Mayur N.

    Current market required faster pace production of smaller, better, and improved products in shorter amount of time. Traditional high-rate manufacturing process such as hot embossing, injection molding, compression molding, etc. use tooling to replicate feature on a products. Miniaturization of many product in the field of biomedical, electronics, optical, and microfluidic is occurring on a daily bases. There is a constant need to produce cheaper, and faster tooling, which can be utilize by existing manufacturing processes. Traditionally, in order to manufacture micron size tooling features processes such as micro-machining, Electrical Discharge Machining (EDM), etc. are utilized. Due to a higher difficulty to produce smaller size features, and longer production cycle time, various additive manufacturing approaches are proposed, e.g. selective laser sintering (SLS), inkjet printing (3DP), fused deposition modeling (FDM), etc. were proposed. Most of these approaches can produce net shaped products from different materials such as metal, ceramic, or polymers. Several attempts were made to produce tooling features using additive manufacturing approaches. Most of these produced tooling were not cost effective, and the life cycle of these tooling was reported short. In this research, a method to produce tooling features using direct printing approach, where highly filled feedstock was dispensed on a substrate. This research evaluated different natural binders, such as guar gum, xanthan gum, and sodium carboxymethyl cellulose (NaCMC) and their combinations were evaluated. The best binder combination was then use to evaluate effect of different metal (316L stainless steel (3 mum), 316 stainless steel (45 mum), and 304 stainless steel (45 mum)) particle size on feature quality. Finally, the effect of direct printing process variables such as dispensing tip internal diameter (500 mum, and 333 mum) at different printing speeds were evaluated.

  15. Evolution equation for the shape function in the parton model approach to inclusive B decays

    Baek, Seungwon; Lee, Kangyoung

    2005-01-01

    We derive an evolution equation for the shape function of the b quark in an analogous way to the Altarelli-Parisi equation by incorporating the perturbative QCD correction to the inclusive semileptonic decays of the B meson. Since the parton picture works well for inclusive B decays due to the heavy mass of the b quark, the scaling feature manifests and the decay rate may be expressed by a single structure function describing the light-cone distribution of the b quark apart from the kinematic factor. The evolution equation introduces a q 2 dependence of the shape function and violates the scaling properties. We solve the evolution equation and discuss the phenomenological implication.

  16. Bipolar Jet Growth and Decline in Hen 3-1341: A Direct Link to Fast Wind and Outburst Evolution

    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...

  17. A review of the irradiation evolution of dispersed oxide nanoparticles in the b.c.c. Fe-Cr system: Current understanding and future directions

    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.

  18. Irradiation-induced void evolution in iron: A phase-field approach with atomistic derived parameters

    Wang Yuan-Yuan; Ding Jian-Hua; Huang Shao-Song; Zhao Ji-Jun; Liu Wen-Bo; Ke Xiao-Qin; Wang Yun-Zhi; Zhang Chi

    2017-01-01

    A series of material parameters are derived from atomistic simulations and implemented into a phase field (PF) model to simulate void evolution in body-centered cubic (bcc) iron subjected to different irradiation doses at different temperatures. The simulation results show good agreement with experimental observations — the porosity as a function of temperature varies in a bell-shaped manner and the void density monotonically decreases with increasing temperatures; both porosity and void density increase with increasing irradiation dose at the same temperature. Analysis reveals that the evolution of void number and size is determined by the interplay among the production, diffusion and recombination of vacancy and interstitial. (paper)

  19. Basic anatomic study of transjugular intrahepatic portosystemic shunt by direct transcaval approach

    Wu Xia; Xu Ke

    2007-01-01

    Objective: To investigate the indications and related anatomic foundation of transjugular intrahepatic portosystemic shunt (TIPS) through direct transcaval approach, and to evaluate the safety, feasibility and clinical significance. Methods: Sixty four patients diagnosed as hepatocirrhosis clinically were involved, including the function of liver Child B (n=40), Child C (n=24). After 2 phrase of hepatic CT enhancement scanning and postprocessing through multiple planner reconstruction (MPR) and curve planner reconstruction (CPR), the data were conjugated statistically by ANOVA. Results: The length of the intrahepatic segment of the inferior cava in Child B is longer than that in Child C (P<0.05). Referring the points of hepatic vein entrance to vena cava as A1, 2 cm away from right hepatic vein as A2, the crotch of portal vein as B1, 2 cm away from right portal vein as B2. The length of A1B1 is shorter than that of A2B1(P<0.05). The angle between A1B2 and right portal vein is smaller than that of A2B2 and right portal vein (P<0.05). Conclusion: Transcaval TIPS creation is safe and feasible, providing the direct transcaval approach as a favorable fluent patency way and less influence on hemodynamics in comparison with traditional TIPS. (authors)

  20. A comparison of direct aspiration versus stent retriever as a first approach ('COMPASS'): protocol.

    Turk, Aquilla S; Siddiqui, Adnan H; Mocco, J

    2018-02-20

    Acute ischemic stroke is a potentially devastating condition and leading cause of morbidity and mortality, affecting an estimated 800 000 people per year in the USA. The natural history of untreated or unrevascularized large vessel occlusions in acute stroke patients results in mortality rates approaching 30%, with only 25% achieving good neurologic outcomes at 90 days. Recently, data have demonstrated that early endovascular recanalization of large vessel occlusions results in better outcomes than medical therapy alone. However, the majority of patients in these studies were treated with a stent retriever based approach. The purpose of COMPASS is to evaluate whether patients treated with a direct aspiration first pass (ADAPT) approach have non-inferior functional outcomes to those treated with a stent retriever as the firstline (SRFL) approach. All patients who meet the inclusion and exclusion criteria and consent to participate will be enrolled at participating centers. Treatment will be randomly assigned by a central web based system in a 1:1 manner to treatment with either ADAPT or SRFL thrombectomy. Statistical methodology is prespecified with details available in the statistical analysis plan. The trial recently completed enrollment, and data collection/verification is ongoing. The final results will be made available on completion of enrollment and follow-up. This paper details the design of the COMPASS trial, a randomized, blinded adjudicator, concurrent, controlled trial of patients treated with either ADAPT or SRFL approaches in order to evaluate whether ADAPT results in non-inferior functional outcome. NCT02466893, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. On irreversible evolutions of two-level systems approaching coherent and squeezed states

    Jurco, B.; Tolar, J.

    1988-01-01

    The concepts of completely positive quantum dynamical semigroups and SU(2)-related generalized coherence and squeezing are used to investigate conditions for Markovian evolutions leading to coherent, intelligent, minimum-uncertainty and squeezed asymptotic stationary states in a 2-level system. (author). 10 refs

  2. Indirect Evolution Versus Strategic Delegation : A Comparison of Two Approaches to Explaining Economic Institutions

    Dufwenberg, M.; Güth, W.

    1997-01-01

    The two major methods of explaining economic institutions, namely by strategic choices or by (indirect) evolution, are compared for the case of a homogenous quadratic duopoly market. Sellers either can provide incentives for their agents to care for sales (amounts) or evolve as sellers who care for

  3. Constructing conditionally integrable evolution systems in (1+1) dimensions: a generalization of invariant modules approach

    Sergyeyev, A.

    2002-01-01

    Given a generalized (Lie-Baecklund) vector field satisfying certain nondegeneracy assumptions, we explicitly describe all (1+1)-dimensional evolution systems that admit this vector field as a generalized conditional symmetry. The connection with the theory of symmetries of systems of ODEs and with the theory of invariant modules is discussed. (author)

  4. Parasite histories and novel phylogenetic tools: alternative approaches to inferring parasite evolution from molecular markers

    Hypša, Václav

    2006-01-01

    Roč. 36, č. 2 (2006), s. 141-155 ISSN 0020-7519 R&D Projects: GA ČR GA206/04/0520 Institutional research plan: CEZ:AV0Z60220518 Keywords : molecular phylogeny * parasite evolution Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2006

  5. Insights into the Diversity of Attitudes Concerning Evolution and Creation: A Multidimensional Approach

    Konneman, Christiane; Asshoff, Roman; Hammann, Marcus

    2016-01-01

    The main aim of this paper is to describe high school students' attitudes concerning evolution and creation, with a focus on (1) attitudes toward evolutionary theory, (2) attitudes toward the Biblical accounts of creation, (3) creationist beliefs, and (4) scientistic beliefs. Latent class analyses revealed seven attitude profiles in a sample of…

  6. A genomic approach to examine the complex evolution of laurasiatherian mammals.

    Björn M Hallström

    Full Text Available Recent phylogenomic studies have failed to conclusively resolve certain branches of the placental mammalian tree, despite the evolutionary analysis of genomic data from 32 species. Previous analyses of single genes and retroposon insertion data yielded support for different phylogenetic scenarios for the most basal divergences. The results indicated that some mammalian divergences were best interpreted not as a single bifurcating tree, but as an evolutionary network. In these studies the relationships among some orders of the super-clade Laurasiatheria were poorly supported, albeit not studied in detail. Therefore, 4775 protein-coding genes (6,196,263 nucleotides were collected and aligned in order to analyze the evolution of this clade. Additionally, over 200,000 introns were screened in silico, resulting in 32 phylogenetically informative long interspersed nuclear elements (LINE insertion events. The present study shows that the genome evolution of Laurasiatheria may best be understood as an evolutionary network. Thus, contrary to the common expectation to resolve major evolutionary events as a bifurcating tree, genome analyses unveil complex speciation processes even in deep mammalian divergences. We exemplify this on a subset of 1159 suitable genes that have individual histories, most likely due to incomplete lineage sorting or introgression, processes that can make the genealogy of mammalian genomes complex. These unexpected results have major implications for the understanding of evolution in general, because the evolution of even some higher level taxa such as mammalian orders may sometimes not be interpreted as a simple bifurcating pattern.

  7. Convergence analysis of directed signed networks via an M-matrix approach

    Meng, Deyuan

    2018-04-01

    This paper aims at solving convergence problems on directed signed networks with multiple nodes, where interactions among nodes are described by signed digraphs. The convergence analysis is achieved by matrix-theoretic and graph-theoretic tools, in which M-matrices play a central role. The fundamental digon sign-symmetry assumption upon signed digraphs can be removed with the proposed analysis approach. Furthermore, necessary and sufficient conditions are established for semi-positive and positive stabilities of Laplacian matrices of signed digraphs, respectively. A benefit of this result is that given strong connectivity, a directed signed network can achieve bipartite consensus (or state stability) if and only if the signed digraph associated with it is structurally balanced (or unbalanced). If the interactions between nodes are described by a signed digraph only with spanning trees, a directed signed network can achieve interval bipartite consensus (or state stability) if and only if the signed digraph contains a structurally balanced (or unbalanced) rooted subgraph. Simulations are given to illustrate the developed results by considering signed networks associated with digon sign-unsymmetric signed digraphs.

  8. Evolution of Radiation Induced Defects in SiC: A Multiscale Simulation Approach

    Jiang, Hao

    temperatures beyond that. Even though clusters cannot diffuse by thermal vibrations, we found they can migrate at room temperature under the influence of electron radiation. This is the first direct observation of radiation-induced diffusion of defect clusters in bulk materials. We show that the underlying mechanism of this athermal diffusion is elastic collision between incoming electrons and cluster atoms. Our findings suggest that defect clusters may be mobile under certain irradiation conditions, changing current understanding of cluster annealing process in irradiated SiC. With the knowledge of cluster diffusion in SiC demonstrated in this thesis, we now become able to predict cluster evolution in SiC with good agreement with experimental measurements. This ability can enable us to estimate changes in many properties of irradiated SiC relevant for its applications in reactors. Internal interfaces such as grain boundaries can behave as sinks to radiation induced defects. The ability of GBs to absorb, transport, and annihilate radiation-induced defects (sink strength) is important to understand radiation response of polycrystalline materials and to better design interfaces for improved resistance to radiation damage. Nowadays, it is established GBs' sink strength is not a static property but rather evolves with many factors, including radiation environments, grain size, and GB microstructure. In this thesis, I investigated the response of small-angle tilt and twist GBs to point defects fluxes in SiC. First of all, I found the pipe diffusion of interstitials in tilt GBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, I show that both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled and can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the

  9. Assessment approaches in massive open online courses: Possibilities, challenges and future directions

    Xiong, Yao; Suen, Hoi K.

    2018-03-01

    The development of massive open online courses (MOOCs) has launched an era of large-scale interactive participation in education. While massive open enrolment and the advances of learning technology are creating exciting potentials for lifelong learning in formal and informal ways, the implementation of efficient and effective assessment is still problematic. To ensure that genuine learning occurs, both assessments for learning (formative assessments), which evaluate students' current progress, and assessments of learning (summative assessments), which record students' cumulative progress, are needed. Providers' more recent shift towards the granting of certificates and digital badges for course accomplishments also indicates the need for proper, secure and accurate assessment results to ensure accountability. This article examines possible assessment approaches that fit open online education from formative and summative assessment perspectives. The authors discuss the importance of, and challenges to, implementing assessments of MOOC learners' progress for both purposes. Various formative and summative assessment approaches are then identified. The authors examine and analyse their respective advantages and disadvantages. They conclude that peer assessment is quite possibly the only universally applicable approach in massive open online education. They discuss the promises, practical and technical challenges, current developments in and recommendations for implementing peer assessment. They also suggest some possible future research directions.

  10. Prospects for direct detection of dark matter in an effective theory approach

    Catena, Riccardo

    2014-01-01

    We perform the first comprehensive analysis of the prospects for direct detection of dark matter with future ton-scale detectors in the general 11-dimensional effective theory of isoscalar dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle. The theory includes 8 momentum and velocity dependent dark matter-nucleon interaction operators, besides the familiar spin-independent and spin-dependent operators. From a variegated sample of 27 benchmark points selected in the parameter space of the theory, we simulate independent sets of synthetic data for ton-scale Germanium and Xenon detectors. From the synthetic data, we then extract the marginal posterior probability density functions and the profile likelihoods of the model parameters. The associated Bayesian credible regions and frequentist confidence intervals allow us to assess the prospects for direct detection of dark matter at the 27 benchmark points. First, we analyze the data assuming the knowledge of the correct dark matter nucleon-interaction type, as it is commonly done for the familiar spin-independent and spin-dependent interactions. Then, we analyze the simulations extracting the dark matter-nucleon interaction type from the data directly, in contrast to standard analyses. This second approach requires an extensive exploration of the full 11-dimensional parameter space of the dark matter-nucleon effective theory. Interestingly, we identify 5 scenarios where the dark matter mass and the dark matter-nucleon interaction type can be reconstructed from the data simultaneously. We stress the importance of extracting the dark matter nucleon-interaction type from the data directly, discussing the main challenges found addressing this complex 11-dimensional problem

  11. Explaining the Evolution of Performance Measures - A Dual Case-Study Approach

    Mohammed Salloum

    2013-07-01

    Full Text Available Few empirical studies have examined how performance measures change in practice and the driving forces behind this change. The existing body of literature has taken a prescriptive approach to how managers and organisations ought to manage change in performance measures without any concern for studying the phenomenon itself and thus a theoretical gap exists. With this gap in mind, the purpose of this paper is to outline how and why the performance measures have changed at two case companies over the time period 2008-2011. In order to fulfil the purpose of this paper two case studies at two different case companies have been conducted. The choice of data collection method is justified by the ambition to attain an in-depth and holistic understanding of the phenomenon. For each case, the data collection was based on four components: an interview study, analysis of archived data, documentation and direct observations. In total, 28 interviews were conducted, 14 at each case company. The empirical findings exhibit that the performance measures are exposed to continuous and considerable change from several perspectives. The measurement scopes at both case companies are steadily expanding, the individual performance measures are constantly replaced and their characteristics are continuously altered. An array of change triggers has been identified in the empirical findings. In contrast to what is advocated in literature, the findings illustrate that the most frequent reason for change is the will to improve the performance measures, the measurement process and the overall performance rather than changing internal and external environments. There are several challenges that need to be addressed in the future research agenda.

  12. Biologist Edwin Grant Conklin and the idea of the religious direction of human evolution in the early 1920s.

    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.

  13. Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

    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

  14. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    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).

  15. Future of DAQ Frameworks and Approaches, and Their Evolution towards the Internet of Things

    Neufeld, Niko

    2015-12-01

    Nowadays, a DAQ system is a complex network of processors, sensors and many other active devices. Historically, providing a framework for DAQ has been a very important role of host institutes of experiments. Reviewing evolution of such DAQ frameworks is a very interesting subject of the conference. “Internet of Things” is a recent buzz word but a DAQ framework could be a good example of IoT.

  16. Modeling the evolution of natural cliffs subject to weathering. 1, Limit analysis approach

    Utili, Stefano; Crosta, Giovanni B.

    2011-01-01

    Retrogressive landsliding evolution of natural slopes subjected to weathering has been modeled by assuming Mohr-Coulomb material behavior and by using an analytical method. The case of weathering-limited slope conditions, with complete erosion of the accumulated debris, has been modeled. The limit analysis upper-bound method is used to study slope instability induced by a homogeneous decrease of material strength in space and time. The only assumption required in the model concerns the degree...

  17. A direct approach to fault-tolerance in measurement-based quantum computation via teleportation

    Silva, Marcus; Danos, Vincent; Kashefi, Elham; Ollivier, Harold

    2007-01-01

    We discuss a simple variant of the one-way quantum computing model (Raussendorf R and Briegel H-J 2001 Phys. Rev. Lett. 86 5188), called the Pauli measurement model, where measurements are restricted to be along the eigenbases of the Pauli X and Y operators, while qubits can be initially prepared both in the vertical bar + π/4 > := 1/√2( vertical bar 0> + e i(π/4) vertical bar 1>) state and the usual vertical bar +> := 1/√2 ( vertical bar 0 > + vertical bar 1>) state. We prove the universality of this quantum computation model, and establish a standardization procedure which permits all entanglement and state preparation to be performed at the beginning of computation. This leads us to develop a direct approach to fault-tolerance by simple transformations of the entanglement graph and preparation operations, while error correction is performed naturally via syndrome-extracting teleportations

  18. State feedback integral control for a rotary direct drive servo valve using a Lyapunov function approach.

    Yu, Jue; Zhuang, Jian; Yu, Dehong

    2015-01-01

    This paper concerns a state feedback integral control using a Lyapunov function approach for a rotary direct drive servo valve (RDDV) while considering parameter uncertainties. Modeling of this RDDV servovalve reveals that its mechanical performance is deeply influenced by friction torques and flow torques; however, these torques are uncertain and mutable due to the nature of fluid flow. To eliminate load resistance and to achieve satisfactory position responses, this paper develops a state feedback control that integrates an integral action and a Lyapunov function. The integral action is introduced to address the nonzero steady-state error; in particular, the Lyapunov function is employed to improve control robustness by adjusting the varying parameters within their value ranges. This new controller also has the advantages of simple structure and ease of implementation. Simulation and experimental results demonstrate that the proposed controller can achieve higher control accuracy and stronger robustness. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  19. Directive approach for Chinese clients receiving psychotherapy: Is that really a priority?

    Chi Ting Connie eNg

    2013-02-01

    Full Text Available The academic literature often suggests that Chinese people prefer directive approaches in therapy. However, studies on this topic are often based on therapists’ self-reports: clients’ perceptions are rarely considered. What does directive approach mean? Is it what clients prefer? Using cultural psychology and medical anthropology as a theoretical framework, the ethnography explored the experience of psychotherapy from Chinese clients’ perspectives. Specifically, using ethnographic interview, eight informants, two male and six female, ranging in age from 40 to 55, were interviewed twice in-depth about their experiences of seeing Chinese therapists. All informants are Chinese immigrants who reside in a major Canadian city and saw at least one Chinese therapist in a community counselling agency within one year prior to the interview. In the first interview, informants created groups of cards describing a list of hypothesized cultural knowledge regarding psychotherapy. After initial data analysis, the cards were presented to the informants in the second interviews, in which they confirmed and/or rejected the hypotheses by grouping, reorganizing, and ranking the cards. In the end each informant created a number of mind-maps with the cards, which served as a representation of informants’ psychological reality of psychotherapy based on their ordinary language. The maps were then further analysed for themes among informants. Results suggest that clients appreciate therapists who give homework, analyse their problems, talk about strategies that other clients have found useful, chat, and provide resources. Results also highlight informants’ understanding of their own responsibility for the therapeutic relationship which has never been documented before and has important clinical implications.

  20. IPIP: A new approach to inverse planning for HDR brachytherapy by directly optimizing dosimetric indices

    Siauw, Timmy; Cunha, Adam; Atamtuerk, Alper; Hsu, I-Chow; Pouliot, Jean; Goldberg, Ken

    2011-01-01

    Purpose: Many planning methods for high dose rate (HDR) brachytherapy require an iterative approach. A set of computational parameters are hypothesized that will give a dose plan that meets dosimetric criteria. A dose plan is computed using these parameters, and if any dosimetric criteria are not met, the process is iterated until a suitable dose plan is found. In this way, the dose distribution is controlled by abstract parameters. The purpose of this study is to develop a new approach for HDR brachytherapy by directly optimizing the dose distribution based on dosimetric criteria. Methods: The authors developed inverse planning by integer program (IPIP), an optimization model for computing HDR brachytherapy dose plans and a fast heuristic for it. They used their heuristic to compute dose plans for 20 anonymized prostate cancer image data sets from patients previously treated at their clinic database. Dosimetry was evaluated and compared to dosimetric criteria. Results: Dose plans computed from IPIP satisfied all given dosimetric criteria for the target and healthy tissue after a single iteration. The average target coverage was 95%. The average computation time for IPIP was 30.1 s on an Intel(R) Core TM 2 Duo CPU 1.67 GHz processor with 3 Gib RAM. Conclusions: IPIP is an HDR brachytherapy planning system that directly incorporates dosimetric criteria. The authors have demonstrated that IPIP has clinically acceptable performance for the prostate cases and dosimetric criteria used in this study, in both dosimetry and runtime. Further study is required to determine if IPIP performs well for a more general group of patients and dosimetric criteria, including other cancer sites such as GYN.

  1. The strategic use of lecture recordings to facilitate an active and self-directed learning approach.

    Topale, Luminica

    2016-08-12

    New learning technologies have the capacity to dramatically impact how students go about learning and to facilitate an active, self-directed learning approach. In U. S. medical education, students encounter a large volume of content, which must be mastered at an accelerated pace. The added pressure to excel on the USMLE Step 1 licensing exam and competition for residency placements, require that students adopt an informed approach to the use of learning technologies so as to enhance rather than to detract from the learning process. The primary aim of this study was to gain a better understanding of how students were using recorded lectures in their learning and how their study habits have been influenced by the technology. Survey research was undertaken using a convenience sample. Students were asked to voluntarily participate in an electronic survey comprised of 27 closed ended, multiple choice questions, and one open ended item. The survey was designed to explore students' perceptions of how recorded lectures affected their choices regarding class participation and impacted their learning and to gain an understanding of how recorded lectures facilitated a strategic, active learning process. Findings revealed that recorded lectures had little influence on students' choices to participate, and that the perceived benefits of integrating recorded lectures into study practices were related to their facilitation of and impact on efficient, active, and self-directed learning. This study was a useful investigation into how the availability of lecture capture technology influenced medical students' study behaviors and how students were making valuable use of the technology as an active learning tool.

  2. Helping patients to reach decisions regarding their treatment: Do 'non-directive' approaches cause systematic bias?

    MacInnes, Joy Anne; Salkovskis, Paul M; Wroe, Abigail; Hope, Tony

    2015-11-01

    does this study add? The hypothetical decision about whether or not, in future, to take statins for elevated cholesterol levels was influenced by positive but not by negative focussing. Results were consistent with the theoretical framework. This study extends previous work on influences on the decision to undertake health screening and vaccination to treatment offered as secondary prevention. 'Non-directive' approaches to helping facilitate decisions can modify those decisions, and as such cannot be regarded as non-directive. © 2015 The British Psychological Society.

  3. Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

    Decaris, Martin L; Leach, J Kent

    2011-04-01

    The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

  4. Pre-directional appliance: A new approach to correct shifted premaxilla in bilateral cleft cases

    P S Daigavane

    2011-01-01

    Full Text Available Management of bilateral cleft lip and palate cases is a challenging task, and if the premaxilla is shifted to either side, it poses a problem for the surgeon to operate and also for the orthodontist to do the orthodontic alignment. The aim of this study was to reposition the shifted premaxilla for better retraction with presurgical infant orthopedics, thus reducing the tissue tension and further scarring which have detrimental effects on maxillary growth. The innovative technique with pre-directional (PD appliance is easy to fabricate and use and works in this direction. Acrylic, springs, permasoft liner, elastics, retentive tapes. Previous approach for the shifted premaxilla was more focused on the surgical correction. In adults, surgery with osteotomy is the only option, with its own limitations and disadvantages, in repositioning the shifted premaxilla. Thus, PD appliance aids to correct the shifted premaxilla in presurgical molding stage. The premaxilla was thus shifted 5.5 mm to the left side, with premaxilla in facial symmetry, with the PD appliance. Presurgical orthopedics with PD appliance is worth in infants with shifted premaxilla in bilateral clefts cases.

  5. A Binary-Encounter-Bethe Approach to Simulate DNA Damage by the Direct Effect

    Plante, Ianik; Cucinotta, Francis A.

    2013-01-01

    The DNA damage is of crucial importance in the understanding of the effects of ionizing radiation. The main mechanisms of DNA damage are by the direct effect of radiation (e.g. direct ionization) and by indirect effect (e.g. damage by.OH radicals created by the radiolysis of water). Despite years of research in this area, many questions on the formation of DNA damage remains. To refine existing DNA damage models, an approach based on the Binary-Encounter-Bethe (BEB) model was developed[1]. This model calculates differential cross sections for ionization of the molecular orbitals of the DNA bases, sugars and phosphates using the electron binding energy, the mean kinetic energy and the occupancy number of the orbital. This cross section has an analytic form which is quite convenient to use and allows the sampling of the energy loss occurring during an ionization event. To simulate the radiation track structure, the code RITRACKS developed at the NASA Johnson Space Center is used[2]. This code calculates all the energy deposition events and the formation of the radiolytic species by the ion and the secondary electrons as well. We have also developed a technique to use the integrated BEB cross section for the bases, sugar and phosphates in the radiation transport code RITRACKS. These techniques should allow the simulation of DNA damage by ionizing radiation, and understanding of the formation of double-strand breaks caused by clustered damage in different conditions.

  6. Application of Direct Assessment Approaches and Methodologies to Cathodically Protected Nuclear Waste Transfer Lines

    Dahl, Megan M.; Pikas, Joseph; Edgemon, Glenn L.; Philo, Sarah

    2013-01-01

    The U.S. Department of Energy's (DOE) Hanford Site is responsible for the safe storage, retrieval, treatment, and disposal of approximately 54 million gallons (204 million liters) of radioactive waste generated since the site's inception in 1943. Today, the major structures involved in waste management at Hanford include 149 carbon steel single-shell tanks, 28 carbon-steel double-shell tanks, plus a network of buried metallic transfer lines and ancillary systems (pits, vaults, catch tanks, etc.) required to store, retrieve, and transfer waste within the tank farm system. Many of the waste management systems at Hanford are still in use today. In response to uncertainties regarding the structural integrity of these systems,' an independent, comprehensive integrity assessment of the Hanford Site piping system was performed. It was found that regulators do not require the cathodically protected pipelines located within the Hanford Site to be assessed by External Corrosion Direct Assessment (ECDA) or any other method used to ensure integrity. However, a case study is presented discussing the application of the direct assessment process on pipelines in such a nuclear environment. Assessment methodology and assessment results are contained herein. An approach is described for the monitoring, integration of outside data, and analysis of this information in order to identify whether coating deterioration accompanied by external corrosion is a threat for these waste transfer lines

  7. THE COST OF PRODUCTION UNDER DIRECT COSTING AND ABSORPTION COSTING – A COMPARATIVE APPROACH

    Bunea-Bontaş Cristina Aurora

    2013-04-01

    Full Text Available Managerial accounting has an important role in strategic management of a company, being designed especially for managers, in order to optimise their decision regarding operating activities. One of the objectives of managerial accounting is the cost calculation, for measuring inventory costs, and the costs and profitability of products and services. Cost calculation systems can vary in terms of which costs are assigned to cost objects, two significant calculation systems being adopted by the costing theory: full cost accounting, which includes all costs of production as product costs, and partial cost accounting, which includes only those costs that vary with output. This article provides a comparative approach regarding the differences between the calculation of the cost of production under direct costing and absorption costing. It also examines the implication of using each of these calculation systems on the financial position and financial performance of the companies reported on the statement of financial position and the income statement. Finally, the advantages of using direct costing for internal reporting are discussed, considering that this method is not acceptable for external reporting to stockholders and other external users.

  8. ARTIFICIAL SELECTION FOR DEVELOPMENTAL TIME IN DROSOPHILA-MELANOGASTER IN RELATION TO THE EVOLUTION OF AGING - DIRECT AND CORRELATED RESPONSES

    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

  9. Grid refinement for aeroacoustics in the lattice Boltzmann method: A directional splitting approach

    Gendre, Félix; Ricot, Denis; Fritz, Guillaume; Sagaut, Pierre

    2017-08-01

    This study focuses on grid refinement techniques for the direct simulation of aeroacoustics, when using weakly compressible lattice Boltzmann models, such as the D3Q19 athermal velocity set. When it comes to direct noise computation, very small errors on the density or pressure field may have great negative consequences. Even strong acoustic density fluctuations have indeed a clearly lower amplitude than the hydrodynamic ones. This work deals with such very weak spurious fluctuations that emerge when a vortical structure crosses a refinement interface, which may contaminate the resulting aeroacoustic field. We show through an extensive literature review that, within the framework described above, this issue has never been addressed before. To tackle this problem, we develop an alternative algorithm and compare its behavior to a classical one, which fits our in-house vertex-centered data structure. Our main idea relies on a directional splitting of the continuous discrete velocity Boltzmann equation, followed by an integration over specific characteristics. This method can be seen as a specific coupling between finite difference and lattice Boltzmann, locally on the interface between the two grids. The method is assessed considering two cases: an acoustic pulse and a convected vortex. We show how very small errors on the density field arise and propagate throughout the domain when a vortical flow crosses the refinement interface. We also show that an increased free stream Mach number (but still within the weakly compressible regime) strongly deteriorates the situation, although the magnitude of the errors may remain negligible for purely aerodynamic studies. A drastically reduced level of error for the near-field spurious noise is obtained with our approach, especially for under-resolved simulations, a situation that is crucial for industrial applications. Thus, the vortex case is proved useful for aeroacoustic validations of any grid refinement algorithm.

  10. Site-Directed Immobilization of BMP-2: Two Approaches for the Production of Innovative Osteoinductive Scaffolds.

    Tabisz, Barbara; Schmitz, Werner; Schmitz, Michael; Luehmann, Tessa; Heusler, Eva; Rybak, Jens-Christoph; Meinel, Lorenz; Fiebig, Juliane E; Mueller, Thomas D; Nickel, Joachim

    2017-03-13

    The regenerative potential of bone is strongly impaired in pathological conditions, such as nonunion fractures. To support bone regeneration various scaffolds have been developed in the past, which have been functionalized with osteogenic growth factors such as bone morphogenetic proteins (BMPs). However, most of them required supra-physiological levels of these proteins leading to burst releases, thereby causing severe side effects. Site-specific, covalent coupling of BMP2 to implant materials might be an optimal strategy in order to overcome these problems. Therefore, we created a BMP-2 variant (BMP2-K3Plk) containing a noncanonical amino acid (propargyl-l-lysine) substitution introduced by genetic code expansion that allows for site-specific and covalent immobilization onto polymeric scaffold materials. To directly compare different coupling strategies, we also produced a BMP2 variant containing an additional cysteine residue (BMP2-A2C) allowing covalent coupling by thioether formation. The BMP2-K3Plk mutant was coupled to functionalized beads by a copper-catalyzed azide-alkyne cycloaddition (CuAAC) either directly or via a short biotin-PEG linker both with high specificity. After exposing the BMP-coated beads to C2C12 cells, ALP expression appeared locally restricted in close proximity to these beads, showing that both coupled BMP2 variants trigger cell differentiation. The advantage of our approach over non-site-directed immobilization techniques is the ability to produce fully defined osteogenic surfaces, allowing for lower BMP2 loads and concomitant higher bioactivities, for example, due to controlled orientation toward BMP2 receptors. Such products might provide superior bone healing capabilities with potential safety advantages as of homogeneous product outcome.

  11. Measuring the CO2 shadow price for wastewater treatment: A directional distance function approach

    Molinos-Senante, María; Hanley, Nick; Sala-Garrido, Ramón

    2015-01-01

    Highlights: • The shadow price of CO 2 informs about the marginal abatement cost of this pollutant. • It is estimated the shadow price of CO 2 for wastewater treatment plants. • The shadow prices depend on the setting of the directional vectors of the distance function. • Sewage sludge treatment technology affects the CO 2 shadow price. - Abstract: The estimation of the value of carbon emissions has become a major research and policy topic since the establishment of the Kyoto Protocol. The shadow price of CO 2 provides information about the marginal abatement cost of this pollutant. It is an essential element in guiding environmental policy issues, since the CO 2 shadow price can be used when fixing carbon tax rates, in environmental cost-benefit analysis and in ascertaining an initial market price for a trading system. The water industry could play an important role in the reduction of greenhouse gas (GHG) emissions. This paper estimates the shadow price of CO 2 for a sample of wastewater treatment plants (WWTPs), using a parametric quadratic directional distance function. Following this, in a sensitivity analysis, the paper evaluates the impact of different settings of directional vectors on the shadow prices. Applying the Mann–Whitney and Kruskal–Wallis non-parametric tests, factors affecting CO 2 prices are investigated. The variation of CO 2 shadow prices across the WWTPs evaluated argues in favour of a market-based approach to CO 2 mitigation as opposed to command-and-control regulation. The paper argues that the estimation of the shadow price of CO 2 for non-power enterprises can provide incentives for reducing GHG emissions

  12. “Table-less” and “Assistant-less” Direct Anterior Approach to Hip Arthroplasty

    Daniel C Allison

    2015-10-01

    Full Text Available In recent years, specialized, non-sterile, traction table systems have facilitated Direct Anterior Approach (DAA hip arthroplasty. To combat the potential downsides of these traction systems, a sterile, intra-operative retractor option has emerged as a means to access the surgical site more easily, minimize soft-tissue trauma, and reduce the degree of required human assistance. This chapter describes the setup, surgical approach, and early results of a retractor system (the Phantom MIS Anterior Hip Retractor system [TeDan Surgical Innovations, Inc. {TSI}, Houston, Texas, US Patent # 8,808,176 B2], which uses a standard operating table, allows preparation of both lower extremities free in the surgical field, is compatible with fluoroscopy, and aids in both acetabular and femoral exposure, preparation, and implantation. Early outcome data indicates that this system significantly minimizes the need for surgical assistance, while allowing for safe and effective DAA performance, facilitating the procedure for high-volume surgeons and shortening the learning curve for surgeons new to the procedure.

  13. Dramatics and education: Different directions and approaches to the application of drama/theatre techniques

    Stamenković Ivana

    2015-01-01

    Full Text Available This paper describes, from the perspective of drama pedagogy, two basic directions in the application of drama and/or theatre techniques in the educational context which mainly differ primarily according to who applies them in practice with children and the young - teachers or professional actors.. Then the most prominent approaches of individual authors are singled out from each agent. Although there are certain similarities among them, we wanted also to show their differences, evident in theoretical, pedagogical and practical orientations. In this context the opinions about the importance of dramatics for education, and about the effects of the use of different approaches, levels and the ways of the application of drama/theatre techniques are singled out, showing at the same time different roles, levels and ways of participating students. This theme is important for promoting dramatics pedagogy, which is not at a high level of development in our country, in spite of the fact that many authors are engaged in theoretical and/or practical work in this area.

  14. DETERMINANTS OF FOREIGN DIRECT INVESTMENT IN NIGERIA: A MARKOV REGIME-SWITCHING APPROACH

    Akinlo A. Enisan

    2017-04-01

    Full Text Available Several studies have analyzed the movement of foreign direct investment in Nigeria using linear approach. In contrast with all existing studies in Nigeria, this paper runs several non linear FDI equations where the main determinants of FDI are determined using Markov- Regime Switching Model (MSMs. The approach enables us to observe structural changes, where exist, in FDI equations through time. Asides, where FDI regression equation is truly nonlinear, MSMs fit data better than the linear models. The paper adopts maximum likelihood methodology of Markov-Regime Model (MSM to identify possible structural changes in level and/or trends and possible changes in parameters of independent variables through the transition probabilities. The results show that FDI process in Nigeria is governed by two different regimes and a shift from one regime to another regime depends on transition probabilities. The results show that the main determinants of FDI are GDP growth, macro instability, financial development, exchange rate, inflation and discount rate. This implies liberalization that stems inflation and enhance the value of domestic currency will attract more FDI into the country.

  15. Chemical evolution of Local Group dwarf galaxies in a cosmological context - I. A new modelling approach and its application to the Sculptor dwarf spheroidal galaxy

    Romano, Donatella; Starkenburg, Else

    2013-09-01

    We present a new approach for chemical evolution modelling, specifically designed to investigate the chemical properties of dwarf galaxies in a full cosmological framework. In particular, we focus on the Sculptor dwarf spheroidal galaxy, for which a wealth of observational data exists, as a test bed for our model. We select four candidate Sculptor-like galaxies from the satellite galaxy catalogue generated by implementation of a version of the Munich semi-analytic model for galaxy formation on the level 2 Aquarius dark matter simulations and use the mass assembly and star formation histories predicted for these four systems as an input for the chemical evolution code. We follow explicitly the evolution of several chemical elements, both in the cold gas out of which the stars form and in the hot medium residing in the halo. We take into account in detail the lifetimes of stars of different initial masses, the distribution of the delay times for Type Ia supernova explosions and the dependence of the stellar yields from the initial metallicity of the stars. We allow large fractions of metals to be deposited into the hot phase, either directly as stars die or through reheated gas flows powered by supernova explosions. We find that, in order to reproduce both the observed metallicity distribution function and the observed abundance ratios of long-lived stars of Sculptor, large fractions of the reheated metals must never re-enter regions of active star formation. With this prescription, all the four analogues to the Sculptor dwarf spheroidal galaxy extracted from the simulated satellites catalogue on the basis of luminosity and stellar population ages are found to reasonably match the detailed chemical properties of real Sculptor stars. However, all model galaxies do severely underestimate the fraction of very metal poor stars observed in Sculptor. Our analysis thus sets further constraints on the semi-analytical models and, at large, on possible metal enrichment

  16. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Almeida A

    2011-08-01

    Full Text Available Laurinda Lemos1,2, Carlos Alegria3, Joana Oliveira3, Ana Machado2, Pedro Oliveira4, Armando Almeida11Life and Health Sciences Research Institute (ICVS, School of Health Sciences, Campus de Gualtar, University of Minho, Braga, Portugal; 2Hospital Center of Alto Ave, Unit of Fafe, Fafe, Portugal; 3Department of Neurosurgery, Hospital São Marcos; 4Products and Systems Engineering, Campus de Azurém, University of Minho, Guimarães, PortugalAbstract: In idiopathic trigeminal neuralgia (TN the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1 a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol], (2 the association of gabapentin (GBP and analgesic block of trigger-points with ropivacaine (ROP (GBP+ROP protocol, and (3 a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol. Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols from cases of idiopathic TN, or selected for MVD surgery (n = 22 due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug

  17. Coastline evolution of Portuguese low-lying sandy coast in the last 50 years: an integrated approach

    Ponte Lira, Cristina; Nobre Silva, Ana; Taborda, Rui; Freire de Andrade, Cesar

    2016-06-01

    Regional/national-scale information on coastline rates of change and trends is extremely valuable, but these studies are scarce. A widely accepted standardized methodology for analysing long-term coastline change has been difficult to achieve, but it is essential to conduct an integrated and holistic approach to coastline evolution and hence support coastal management actions. Additionally, databases providing knowledge on coastline evolution are of key importance to support both coastal management experts and users.The main objective of this work is to present the first systematic, national-scale and consistent long-term coastline evolution data of Portuguese mainland low-lying sandy coasts.The methodology used quantifies coastline evolution using a unique and robust coastline indicator (the foredune toe), which is independent of short-term changes.The dataset presented comprises (1) two polyline sets, mapping the 1958 and 2010 sandy beach-dune system coastline, both optimized for working at 1 : 50 000 scale or smaller; (2) one polyline set representing long-term change rates between 1958 and 2010, each estimated at 250 m; and (3) a table with minimum, maximum and mean of evolution rates for sandy beach-dune system coastline. All science data produced here are openly accessible at https://doi.pangaea.de/10.1594/PANGAEA.859136 and can be used in other studies.Results show beach erosion as the dominant trend, with a mean change rate of -0.24 ± 0.01 m year-1 for all mainland Portuguese beach-dune systems. Although erosion is dominant, this evolution is variable in signal and magnitude in different coastal sediment cells and also within each cell. The most relevant beach erosion issues were found in the coastal stretches of Espinho-Torreira and Costa Nova-Praia de Mira, Cova da Gala-Leirosa, and Cova do Vapor-Costa da Caparica. The coastal segments Minho River-Nazaré and Costa da Caparica adjacent to the coast exhibit a history of major human interventions

  18. An Investigation of Turkish Middle School Science Teachers' Pedagogical Orientations Towards Direct and Inquiry Instructional Approaches

    Sahingoz, Selcuk

    One of the most important goals of science education is preparing effective science teachers which includes the development of a science pedagogical orientation. Helping in-service science teachers improve their orientations toward science teaching begins with identifying their current orientations. While there are many aspects of an effective science teaching orientation, this study specifically focuses on effective pedagogy. The interest of this study is to clarify pedagogical orientations of middle school science teachers in Turkey toward the teaching of science conceptual knowledge. It focuses on what instructional preferences Turkish middle school science teachers have in theory and practice. The purpose of this study is twofold: 1) to elucidate teacher pedagogical profiles toward direct and inquiry instructional approaches. For this purpose, quantitative profile data, using a Turkish version of the Pedagogy of Science Teaching Test (POSTT-TR) assessment instrument, was collected from 533 Turkish middle school science teachers; 2) to identify teaching orientations of middle school science teachers and to identify their reasons for preferring specific instructional practices. For this purpose, descriptive qualitative, interview data was collected from 23 teachers attending a middle school science teacher workshop in addition to quantitative data using the POSTT-TR. These teachers sat for interviews structured by items from the POSTT-TR. Thus, the research design is mixed-method. The design provides a background profile on teacher orientations along with insights on reasons for pedagogical choices. The findings indicate that instructional preference distributions for the large group and smaller group are similar; however, the smaller workshop group is more in favor of inquiry instructional approaches. The findings also indicate that Turkish middle school science teachers appear to have variety of teaching orientations and they have varied reasons. Moreover, the

  19. Hydrochemical evolution and groundwater flow processes in the Galilee and Eromanga basins, Great Artesian Basin, Australia: a multivariate statistical approach.

    Moya, Claudio E; Raiber, Matthias; Taulis, Mauricio; Cox, Malcolm E

    2015-03-01

    The Galilee and Eromanga basins are sub-basins of the Great Artesian Basin (GAB). In this study, a multivariate statistical approach (hierarchical cluster analysis, principal component analysis and factor analysis) is carried out to identify hydrochemical patterns and assess the processes that control hydrochemical evolution within key aquifers of the GAB in these basins. The results of the hydrochemical assessment are integrated into a 3D geological model (previously developed) to support the analysis of spatial patterns of hydrochemistry, and to identify the hydrochemical and hydrological processes that control hydrochemical variability. In this area of the GAB, the hydrochemical evolution of groundwater is dominated by evapotranspiration near the recharge area resulting in a dominance of the Na-Cl water types. This is shown conceptually using two selected cross-sections which represent discrete groundwater flow paths from the recharge areas to the deeper parts of the basins. With increasing distance from the recharge area, a shift towards a dominance of carbonate (e.g. Na-HCO3 water type) has been observed. The assessment of hydrochemical changes along groundwater flow paths highlights how aquifers are separated in some areas, and how mixing between groundwater from different aquifers occurs elsewhere controlled by geological structures, including between GAB aquifers and coal bearing strata of the Galilee Basin. The results of this study suggest that distinct hydrochemical differences can be observed within the previously defined Early Cretaceous-Jurassic aquifer sequence of the GAB. A revision of the two previously recognised hydrochemical sequences is being proposed, resulting in three hydrochemical sequences based on systematic differences in hydrochemistry, salinity and dominant hydrochemical processes. The integrated approach presented in this study which combines different complementary multivariate statistical techniques with a detailed assessment of the

  20. Hamiltonian approach to the derivation of evolution equations for wave trains in weakly unstable media

    N. N. Romanova

    1998-01-01

    Full Text Available The dynamics of weakly nonlinear wave trains in unstable media is studied. This dynamics is investigated in the framework of a broad class of dynamical systems having a Hamiltonian structure. Two different types of instability are considered. The first one is the instability in a weakly supercritical media. The simplest example of instability of this type is the Kelvin-Helmholtz instability. The second one is the instability due to a weak linear coupling of modes of different nature. The simplest example of a geophysical system where the instability of this and only of this type takes place is the three-layer model of a stratified shear flow with a continuous velocity profile. For both types of instability we obtain nonlinear evolution equations describing the dynamics of wave trains having an unstable spectral interval of wavenumbers. The transformation to appropriate canonical variables turns out to be different for each case, and equations we obtained are different for the two types of instability we considered. Also obtained are evolution equations governing the dynamics of wave trains in weakly subcritical media and in media where modes are coupled in a stable way. Presented results do not depend on a specific physical nature of a medium and refer to a broad class of dynamical systems having the Hamiltonian structure of a special form.

  1. Controversy in Biology Classrooms—Citizen Science Approaches to Evolution and Applications to Climate Change Discussions

    Rachel A. Yoho

    2015-11-01

    Full Text Available The biological sciences encompass topics considered controversial by the American public, such as evolution and climate change. We believe that the development of climate change education in the biology classroom is better informed by an understanding of the history of the teaching of evolution. A common goal for science educators should be to engender a greater respect for and appreciation of science among students while teaching specific content knowledge. Citizen science has emerged as a viable yet underdeveloped method for engaging students of all ages in key scientific issues that impact society through authentic data-driven scientific research. Where successful, citizen science may open avenues of communication and engagement with the scientific process that would otherwise be more difficult to achieve. Citizen science projects demonstrate versatility in education and the ability to test hypotheses by collecting large amounts of often publishable data. We find a great possibility for science education research in the incorporation of citizen science projects in curriculum, especially with respect to “hot topics” of socioscientific debate based on our review of the findings of other authors.

  2. Semi-classical approaches to the phase space evolutions in intermediate energy heavy ion collisions

    Remaud, B; Sebille, F; Raffray, Y; Gregoire, C; Vinet, L

    1986-01-06

    The properties of semi-classical phase space evolution equations - as the Vlasov/Boltzmann equations - are discussed in the context of the heavy ion reaction theory at intermediate energies (from 10 to 100 MeV per nucleon). The generalized coherent state set is shown to form a (over) complete basis for the phase space; then every solution of the Vlasov/Boltzmann equations can be defined as a convolution product of the generalized coherent state basis by an appropriate weight function w. The uniform approximation for w is shown to provide an accurate semi-classical description of fermion systems in their ground state: the examples of fermions in a harmonic well and of cold nuclei are discussed. The solution of the Vlasov equation amounts to follow the time evolution of the coherent states which play the role of a moving basis. For the Boltzmann equation, the collision term is taken into account by explicit or implicit variations of the function w. Typical applications are discussed: nuclear response to the giant monopole resonance excitation, fast nucleon emission in heavy-ion reactions. (orig.).

  3. Alteration of 'R7T7' type nuclear glasses: statistical approach, experimental validation, local evolution model

    Thierry, F.

    2003-02-01

    The aim of this work is to propose an evolution of nuclear (R7T7-type) glass alteration modeling. The first part of this thesis is about development and validation of the 'r(t)' model. This model which predicts the decrease of alteration rates in confined conditions is based upon a coupling between a first-order dissolution law and a diffusion barrier effect of the alteration gel layer. The values and the uncertainties regarding the main adjustable parameters of the model (α, Dg and C*) have been determined from a systematic study of the available experimental data. A program called INVERSION has been written for this purpose. This work lead to characterize the validity domain of the 'r(t)' model and to parametrize it. Validation experiments have been undertaken, confirming the validity of the parametrization over 200 days. A new model is proposed in the second part of this thesis. It is based on an inhibition of glass dissolution reaction by silicon coupled with a local description of silicon retention in the alteration gel layer. This model predicts the evolutions of boron and silicon concentrations in solution as well as the concentrations and retention profiles in the gel layer. These predictions have been compared to measurements of retention profiles by the secondary ion mass spectrometry (SIMS) method. The model has been validated on fractions of gel layer which reactivity present low or moderate disparities. (author)

  4. Managing the Evolution of an Enterprise Architecture using a MAS-Product-Line Approach

    Pena, Joaquin; Hinchey, Michael G.; Resinas, manuel; Sterritt, Roy; Rash, James L.

    2006-01-01

    We view an evolutionary system ns being n software product line. The core architecture is the unchanging part of the system, and each version of the system may be viewed as a product from the product line. Each "product" may be described as the core architecture with sonre agent-based additions. The result is a multiagent system software product line. We describe an approach to such n Software Product Line-based approach using the MaCMAS Agent-Oriented nzethoclology. The approach scales to enterprise nrchitectures as a multiagent system is an approprinre means of representing a changing enterprise nrchitectclre nnd the inferaction between components in it.

  5. The Pedagogical Orientations of South African Physical Sciences Teachers Towards Inquiry or Direct Instructional Approaches

    Ramnarain, Umesh; Schuster, David

    2014-08-01

    In recent years, inquiry-based science instruction has become widely advocated in science education standards in many countries and, hence, in teacher preparation programmes. Nevertheless, in practice, one finds a wide variety of science instructional approaches. In South Africa, as in many countries, there is also a great disparity in school demographic situations, which can also affect teaching practices. This study investigated the pedagogical orientations of in-service physical sciences teachers at a diversity of schools in South Africa. Assessment items in a Pedagogy of Science Teaching Test (POSTT) were used to identify teachers' science teaching orientations, and reasons for pedagogical choices were probed in interviews. The findings reveal remarkable differences between the orientations of teachers at disadvantaged township schools and teachers at more privileged suburban schools. We found that teachers at township schools have a strong `active direct' teaching orientation overall, involving direct exposition of the science followed by confirmatory practical work, while teachers at suburban schools exhibit a guided inquiry orientation, with concepts being developed via a guided exploration phase. The study identified contextual factors such as class size, availability of resources, teacher competence and confidence, time constraints, student ability, school culture and parents' expectations as influencing the methods adopted by teachers. In view of the recent imperative for inquiry-based learning in the new South African curriculum, this study affirms the context specificity of curriculum implementation (Bybee 1993) and suggests situational factors beyond the curriculum mandate that need to be addressed to achieve successful inquiry-based classroom instruction in science.

  6. On the nature of fur evolution: A phylogenetic approach in Actinobacteria

    Benson David R

    2008-06-01

    Full Text Available Abstract Background An understanding of the evolution of global transcription regulators is essential for comprehending the complex networks of cellular metabolism that have developed among related organisms. The fur gene encodes one of those regulators – the ferric uptake regulator Fur – widely distributed among bacteria and known to regulate different genes committed to varied metabolic pathways. On the other hand, members of the Actinobacteria comprise an ecologically diverse group of bacteria able to inhabit various natural environments, and for which relatively little is currently understood concerning transcriptional regulation. Results BLAST analyses revealed the presence of more than one fur homologue in most members of the Actinobacteria whose genomes have been fully sequenced. We propose a model to explain the evolutionary history of fur within this well-known bacterial phylum: the postulated scenario includes one duplication event from a primitive regulator, which probably had a broad range of co-factors and DNA-binding sites. This duplication predated the appearance of the last common ancestor of the Actinobacteria, while six other duplications occurred later within specific groups of organisms, particularly in two genera: Frankia and Streptomyces. The resulting paralogues maintained main biochemical properties, but became specialised for regulating specific functions, coordinating different metal ions and binding to unique DNA sequences. The presence of syntenic regions surrounding the different fur orthologues supports the proposed model, as do the evolutionary distances and topology of phylogenetic trees built using both Neighbor-Joining and Maximum-Likelihood methods. Conclusion The proposed fur evolutionary model, which includes one general duplication and two in-genus duplications followed by divergence and specialization, explains the presence and diversity of fur genes within the Actinobacteria. Although a few rare

  7. Characteristics of a direct methanol fuel cell system with the time shared fuel supplying approach

    Na, Youngseung; Kwon, Jungmin; Kim, Hyun; Cho, Hyejung; Song, Inseob

    2013-01-01

    DMFC (direct methanol fuel cell) systems usually employ two pumps for supplying the methanol solution. The conventional system configuration, however, may bring about free flow from the methanol reservoir and malfunctions in the self-priming of the pumps. When instruments such as check valves and pressure regulators are applied, they result in excessive weight and control system malfunctions. In this paper, a light and robust DMFC system is proposed. By using the time sharing approach to supply fuel with a 3-way valve, free flow does not occur because only one inlet is opened at one time which means that both the circulation flow from gas liquid separator and the fuel flow from the methanol cartridge are not allowed to be opened at same time. As a result, back flow and self-priming problems do not occur. This makes the system stable and robust due to the removal of both the check valves and the fluctuation from unstable back pressure. Stabilized system doesn't need excessive battery buffering and recycling water any more, which are responsible for the heavy system. The proposed system performs the same level of power and efficiency with the conventional system. Adaptability is also carried out in various environmental temperature conditions. - Highlights: ►A light and robust DMFC system is proposed. ► The circulation pump is able to self-prime by itself after long term storage. ► The time sharing approach to supply fuel enables to control the methanol concentration precisely. ► The methanol concentration is controlled without free flow and the back flow from the fuel feeding pump. ► The excessive buffer of the batteries and the recycling water level are reduced

  8. A Review of Player Monitoring Approaches in Basketball: Current Trends and Future Directions.

    Fox, Jordan L; Scanlan, Aaron T; Stanton, Robert

    2017-07-01

    Fox, JL, Scanlan, AT, and Stanton, R. A review of player monitoring approaches in basketball: current trends and future directions. J Strength Cond Res 31(7): 2021-2029, 2017-Effective monitoring of players in team sports such as basketball requires an understanding of the external demands and internal responses, as they relate to training phases and competition. Monitoring of external demands and internal responses allows coaching staff to determine the dose-response associated with the imposed training load (TL), and subsequently, if players are adequately prepared for competition. This review discusses measures reported in the literature for monitoring the external demands and internal responses of basketball players during training and competition. The external demands of training and competition were primarily monitored using time-motion analysis, with limited use of microtechnology being reported. Internal responses during training were typically measured using hematological markers, heart rate, various TL models, and perceptual responses such as rating of perceived exertion (RPE). Heart rate was the most commonly reported indicator of internal responses during competition with limited reporting of hematological markers or RPE. These findings show a large discrepancy between the reporting of external and internal measures and training and competition demands. Microsensors, however, may be a practical and convenient method of player monitoring in basketball to overcome the limitations associated with current approaches while allowing for external demands and internal responses to be recorded simultaneously. The triaxial accelerometers of microsensors seem well suited for basketball and warrant validation to definitively determine their place in the monitoring of basketball players. Coaching staff should make use of this technology by tracking individual player responses across the annual plan and using real-time monitoring to minimize factors such as fatigue

  9. From Microactions to Macrostructure and Back : A Structurational Approach to the Evolution of Organizational Networks

    Whitbred, Robert; Fonti, Fabio; Steglich, Christian; Contractor, Noshir

    Structuration theory (ST) and network analysis are promising approaches for studying the emergence of communication networks. We offer a model that integrates the conceptual richness of structuration with the precision of relevant concepts and mechanisms offered from communication network research.

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

    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.

  11. Functional evolution and structural conservation in chimeric cytochromes p450: calibrating a structure-guided approach.

    Otey, Christopher R; Silberg, Jonathan J; Voigt, Christopher A; Endelman, Jeffrey B; Bandara, Geethani; Arnold, Frances H

    2004-03-01

    Recombination generates chimeric proteins whose ability to fold depends on minimizing structural perturbations that result when portions of the sequence are inherited from different parents. These chimeric sequences can display functional properties characteristic of the parents or acquire entirely new functions. Seventeen chimeras were generated from two CYP102 members of the functionally diverse cytochrome p450 family. Chimeras predicted to have limited structural disruption, as defined by the SCHEMA algorithm, displayed CO binding spectra characteristic of folded p450s. Even this small population exhibited significant functional diversity: chimeras displayed altered substrate specificities, a wide range in thermostabilities, up to a 40-fold increase in peroxidase activity, and ability to hydroxylate a substrate toward which neither parent heme domain shows detectable activity. These results suggest that SCHEMA-guided recombination can be used to generate diverse p450s for exploring function evolution within the p450 structural framework.

  12. Adaptive Differential Evolution Approach for Constrained Economic Power Dispatch with Prohibited Operating Zones

    Abdellatif HAMOUDA

    2011-12-01

    Full Text Available Economic power dispatch (EPD is one of the main tools for optimal operation and planning of modern power systems. To solve effectively the EPD problem, most of the conventional calculus methods rely on the assumption that the fuel cost characteristic of a generating unit is a continuous and convex function, resulting in inaccurate dispatch. This paper presents the design and application of efficient adaptive differential evolution (ADE algorithm for the solution of the economic power dispatch problem, where the non-convex characteristics of the generators, such us prohibited operating zones and ramp rate limits of the practical generator operation are considered. The 26 bus benchmark test system with 6 units having prohibited operating zones and ramp rate limits was used for testing and validation purposes. The results obtained demonstrate the effectiveness of the proposed method for solving the non-convex economic dispatch problem.

  13. Direct expansion solar assisted heat pumps – A clean steady state approach for overall performance analysis

    Tagliafico, Luca A.; Scarpa, Federico; Valsuani, Federico

    2014-01-01

    Traditional thermal solar panel technologies have limited efficiency and the required economic investments make them noncompetitive in the space heating market. The greatest limit to the diffusion of thermal solar systems is the characteristic temperatures they can reach: the strong connection between the user temperature and the collector temperature makes it possible to achieve high thermal (collector) efficiency only at low, often useless, user temperatures. By using solar collectors as thermal exchange units (evaporators) in a heat pump system (direct expansion solar assisted heat pump, DX-SAHP), the overall efficiency greatly increases with a significative cut of the associated investment in terms of pay-back time. In this study, an approach is proposed to the steady state analysis of DX-SAHP, which is based on the simplified inverse Carnot cycle and on the second law efficiency concept. This method, without the need of calculating the refrigerant fluid properties and the detailed processes occurring in the refrigeration device, allows us to link the main features of the plant to its relevant interactions with the surroundings. The very nature of the proposed method makes the relationship explicit and meaningful among all the involved variables. The paper, after the description of the method, presents an explanatory application of this technique by reviewing various aspects of the performance of a typical DX-SAHP in which the savings on primary energy consumption is regarded as the main feature of the plant and highlighted in a monthly averaged analysis. Results agree to those coming from a common standard steady state thermodynamic analysis. The application to a typical DX-SAHP system demonstrates that a mean saved primary energy of about 50% with respect to standard gas burner can be achieved for the same user needs. Such a result is almost independent from the type of flat plate solar panel used (double or single glazed, or even bare panels) as a result of

  14. Assessing eco-efficiency: A metafrontier directional distance function approach using life cycle analysis

    Beltrán-Esteve, Mercedes; Reig-Martínez, Ernest; Estruch-Guitart, Vicent

    2017-01-01

    Sustainability analysis requires a joint assessment of environmental, social and economic aspects of production processes. Here we propose the use of Life Cycle Analysis (LCA), a metafrontier (MF) directional distance function (DDF) approach, and Data Envelopment Analysis (DEA), to assess technological and managerial differences in eco-efficiency between production systems. We use LCA to compute six environmental and health impacts associated with the production processes of nearly 200 Spanish citrus farms belonging to organic and conventional farming systems. DEA is then employed to obtain joint economic-environmental farm's scores that we refer to as eco-efficiency. DDF allows us to determine farms' global eco-efficiency scores, as well as eco-efficiency scores with respect to specific environmental impacts. Furthermore, the use of an MF helps us to disentangle technological and managerial eco-inefficiencies by comparing the eco-efficiency of both farming systems with regards to a common benchmark. Our core results suggest that the shift from conventional to organic farming technology would allow a potential reduction in environmental impacts of 80% without resulting in any decline in economic performance. In contrast, as regards farmers' managerial capacities, both systems display quite similar mean scores.

  15. Assessing eco-efficiency: A metafrontier directional distance function approach using life cycle analysis

    Beltrán-Esteve, Mercedes, E-mail: mercedes.beltran@uv.es [Department of Applied Economics II, University of Valencia (Spain); Reig-Martínez, Ernest [Department of Applied Economics II, University of Valencia, Ivie (Spain); Estruch-Guitart, Vicent [Department of Economy and Social Sciences, Polytechnic University of Valencia (Spain)

    2017-03-15

    Sustainability analysis requires a joint assessment of environmental, social and economic aspects of production processes. Here we propose the use of Life Cycle Analysis (LCA), a metafrontier (MF) directional distance function (DDF) approach, and Data Envelopment Analysis (DEA), to assess technological and managerial differences in eco-efficiency between production systems. We use LCA to compute six environmental and health impacts associated with the production processes of nearly 200 Spanish citrus farms belonging to organic and conventional farming systems. DEA is then employed to obtain joint economic-environmental farm's scores that we refer to as eco-efficiency. DDF allows us to determine farms' global eco-efficiency scores, as well as eco-efficiency scores with respect to specific environmental impacts. Furthermore, the use of an MF helps us to disentangle technological and managerial eco-inefficiencies by comparing the eco-efficiency of both farming systems with regards to a common benchmark. Our core results suggest that the shift from conventional to organic farming technology would allow a potential reduction in environmental impacts of 80% without resulting in any decline in economic performance. In contrast, as regards farmers' managerial capacities, both systems display quite similar mean scores.

  16. Quality by design approach: application of artificial intelligence techniques of tablets manufactured by direct compression.

    Aksu, Buket; Paradkar, Anant; de Matas, Marcel; Ozer, Ozgen; Güneri, Tamer; York, Peter

    2012-12-01

    The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the "knowledge space" is a summary of all process knowledge obtained during product development, and the "design space" is the area in which a product can be manufactured within acceptable limits. To create the spaces, artificial neural networks (ANNs) can be used to emphasize the multidimensional interactions of input variables and to closely bind these variables to a design space. This helps guide the experimental design process to include interactions among the input variables, along with modeling and optimization of pharmaceutical formulations. The objective of this study was to develop an integrated multivariate approach to obtain a quality product based on an understanding of the cause-effect relationships between formulation ingredients and product properties with ANNs and genetic programming on the ramipril tablets prepared by the direct compression method. In this study, the data are generated through the systematic application of the design of experiments (DoE) principles and optimization studies using artificial neural networks and neurofuzzy logic programs.

  17. Polymer density functional theory approach based on scaling second-order direct correlation function.

    Zhou, Shiqi

    2006-06-01

    A second-order direct correlation function (DCF) from solving the polymer-RISM integral equation is scaled up or down by an equation of state for bulk polymer, the resultant scaling second-order DCF is in better agreement with corresponding simulation results than the un-scaling second-order DCF. When the scaling second-order DCF is imported into a recently proposed LTDFA-based polymer DFT approach, an originally associated adjustable but mathematically meaningless parameter now becomes mathematically meaningful, i.e., the numerical value lies now between 0 and 1. When the adjustable parameter-free version of the LTDFA is used instead of the LTDFA, i.e., the adjustable parameter is fixed at 0.5, the resultant parameter-free version of the scaling LTDFA-based polymer DFT is also in good agreement with the corresponding simulation data for density profiles. The parameter-free version of the scaling LTDFA-based polymer DFT is employed to investigate the density profiles of a freely jointed tangent hard sphere chain near a variable sized central hard sphere, again the predictions reproduce accurately the simulational results. Importance of the present adjustable parameter-free version lies in its combination with a recently proposed universal theoretical way, in the resultant formalism, the contact theorem is still met by the adjustable parameter associated with the theoretical way.

  18. Numerical Methods Application for Reinforced Concrete Elements-Theoretical Approach for Direct Stiffness Matrix Method

    Sergiu Ciprian Catinas

    2015-07-01

    Full Text Available A detailed theoretical and practical investigation of the reinforced concrete elements is due to recent techniques and method that are implemented in the construction market. More over a theoretical study is a demand for a better and faster approach nowadays due to rapid development of the calculus technique. The paper above will present a study for implementing in a static calculus the direct stiffness matrix method in order capable to address phenomena related to different stages of loading, rapid change of cross section area and physical properties. The method is a demand due to the fact that in our days the FEM (Finite Element Method is the only alternative to such a calculus and FEM are considered as expensive methods from the time and calculus resources point of view. The main goal in such a method is to create the moment-curvature diagram in the cross section that is analyzed. The paper above will express some of the most important techniques and new ideas as well in order to create the moment curvature graphic in the cross sections considered.

  19. Metagenomic approaches for direct and cell culture evaluation of the virological quality of wastewater

    Aw, Tiong Gim; Howe, Adina; Rose, Joan B.

    2014-12-01

    Genomic-based molecular techniques are emerging as powerful tools that allow a comprehensive characterization of water and wastewater microbiomes. Most recently, next generation sequencing (NGS) technologies which produce large amounts of sequence data are beginning to impact the field of environmental virology. In this study, NGS and bioinformatics have been employed for the direct detection and characterization of viruses in wastewater and of viruses isolated after cell culture. Viral particles were concentrated and purified from sewage samples by polyethylene glycol precipitation. Viral nucleic acid was extracted and randomly amplified prior to sequencing using Illumina technology, yielding a total of 18 million sequence reads. Most of the viral sequences detected could not be characterized, indicating the great viral diversity that is yet to be discovered. This sewage virome was dominated by bacteriophages and contained sequences related to known human pathogenic viruses such as adenoviruses (species B, C and F), polyomaviruses JC and BK and enteroviruses (type B). An array of other animal viruses was also found, suggesting unknown zoonotic viruses. This study demonstrated the feasibility of metagenomic approaches to characterize viruses in complex environmental water samples.

  20. Direct-puncture approach to the extraconal portion of the superior ophthalmic vein for carotid cavernous fistulae

    Kurata, A.; Suzuki, S.; Iwamoto, K.; Miyazaki, T.; Inukai, M.; Abe, K.; Niki, J.; Yamada, M.; Fujii, K.; Kan, S.

    2009-01-01

    The transvenous approach via the superior ophthalmic vein (SOV) is an available approach for carotid cavernous fistula (CCF), especially in the event that there is no other suitable approach route to the fistula. Surgical exposure of the peripheral roots of the SOV is commonly used; however, often, the SOV is often not accessible because of anatomical problems and/or complications. In this paper, we present and discuss our original direct-puncture approach to the extraconal portion of the SOV. An attempt on three patients with traumatic CCF failed with the transarterial approach and the conventional venous approach via the inferior petrosal sinus; therefore, the patients were treated with the direct-puncture approach to the extraconal portion of the SOV using two-dimensional digital subtraction angiography with local anesthesia. All cases that had tortuous and partially stenotic division of the SOV were treated successfully with this approach and without complications. This approach will become an alternate approach, especially when the peripheral roots of the SOV are focally narrowed and tortuous, making it impossible to insert a catheter. (orig.)

  1. Global Risk Evolution and Diversification: a Copula-DCC-GARCH Model Approach

    Marcelo Brutti Righi

    2012-12-01

    Full Text Available In this paper we estimate a dynamic portfolio composed by the U.S., German, British, Brazilian, Hong Kong and Australian markets, the period considered started on September 2001 and finished in September 2011. We ran the Copula-DCC-GARCH model on the daily returns conditional covariance matrix. The results allow us to conclude that there were changes in portfolio composition, occasioned by modifications in volatility and dependence between markets. The dynamic approach significantly reduced the portfolio risk if compared to the traditional static approach, especially in turbulent periods. Furthermore, we verified that the estimated copula model outperformed the conventional DCC model for the sample studied.

  2. Microstructural evolution of direct chill cast Al-15.5Si-4Cu-1Mg-1Ni-0.5Cr alloy during solution treatment

    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...

  3. Maxillary sinus floor elevation via crestal approach: the evolution of the hydraulic pressure technique.

    Lopez, Michele Antonio; Andreasi Bassi, Mirko; Confalone, Luca; Carinci, Francesco

    2014-01-01

    The current study describes an innovative protocol for the surgical maxillary sinus augmentation via a crestal approach that uses hydraulic pressure to lift the Schneiderian membrane and simultaneously fill the subantral space with a biomaterial for bone regeneration (nanocrystalline hydroxyapatite in aqueous solution). The technique in question combines the advantages of large amounts of grafted biomaterial with reduced trauma, high precision, and predictability.

  4. Simulation of microstructure evolution in fused-coating additive manufacturing based on phase field approach

    Ru-wei Geng

    2017-11-01

    Full Text Available The mechanical properties of metal components are determined by the solidification behaviour and microstructure. A quantitative phase field model is used to investigate the microstructure evolution of fused-coating additive manufacturing, by which to improve the quality of deposition. During the fused-coating process, the molten metal in a crucible flows out of a nozzle and then reaches the substrate. The solidification happens at the moment when the molten metal comes into contact with substrate moving in three-dimensional space. The macroscopic heat transfer model of fused-coating is established to get the temperature field considered as the initial temperature boundary conditions in the phase field model. The numerical and experimental results show that the morphology of grains varies with different solidification environments. Columnar grains are observed during the early period at the bottom of fused-coating layer and the equiaxed grains appear subsequently ahead of the columnar grains. Columnar dendrites phase field simulations about the grains morphology and solute distribution are conducted considering the solidification environments. The simulation results are in good agreement with experimental results.

  5. A geochronological approach for cave evolution in the Cantabrian Coast (Pindal Cave, NW Spain)

    Jimenez-Sanchez, M.; Bischoff, J.L.; Stoll, H.; Aranburu, A.

    2006-01-01

    Some of the oldest speleothems in the North Cantabrian Coast (Spain) are reported for the first time in this work. Pindal Cave is developed at 24 m above sea level, in a karstic massif reaching its highest surface in a marine terrace (rasa) located at 50-64 m above the present sea level. Several phases of evolution were previously recognized into the cave, including block collapse of the roof, episodic flooding and detrital sedimentation, and chemical precipitation of at least four speleothem generations over both alluvial and collapse deposits. Three of these speleothem generations have been dated by U/Th. The first generation yielded ages from 124,2 ?? 1, 5 ka BP to 73,1 ?? 0,9 ka BP, giving a minimum age for the main detritic sediments in the cave. The second one is not dated. The third generation gives an age of 3,71 ?? 0,4 ka BP (mathematically corrected to 2.7 ?? 0.5 ka BP), while for the youngest generation, with actively growing stalagmites in the cave, basal ages of 200 years BP are estimated by counting annual laminae. The data suggest a tentative maximum elevation rate close to 0, 2 mm/yr for the Cantabrian Margin in this area, although further chronological studies will be needed to check this hypothesis. ?? 2006 Gebru??der Borntraeger.

  6. Approach in Theory of Nonlinear Evolution Equations: The Vakhnenko-Parkes Equation

    V. O. Vakhnenko

    2016-01-01

    Full Text Available A variety of methods for examining the properties and solutions of nonlinear evolution equations are explored by using the Vakhnenko equation (VE as an example. The VE, which arises in modelling the propagation of high-frequency waves in a relaxing medium, has periodic and solitary traveling wave solutions some of which are loop-like in nature. The VE can be written in an alternative form, known as the Vakhnenko-Parkes equation (VPE, by a change of independent variables. The VPE has an N-soliton solution which is discussed in detail. Individual solitons are hump-like in nature whereas the corresponding solution to the VE comprises N-loop-like solitons. Aspects of the inverse scattering transform (IST method, as applied originally to the KdV equation, are used to find one- and two-soliton solutions to the VPE even though the VPE’s spectral equation is third-order and not second-order. A Bäcklund transformation for the VPE is used to construct conservation laws. The standard IST method for third-order spectral problems is used to investigate solutions corresponding to bound states of the spectrum and to a continuous spectrum. This leads to N-soliton solutions and M-mode periodic solutions, respectively. Interactions between these types of solutions are investigated.

  7. Evolution of feeding specialization in Tanganyikan scale-eating cichlids: a molecular phylogenetic approach

    Nishida Mutsumi

    2007-10-01

    Full Text Available Abstract Background Cichlid fishes in Lake Tanganyika exhibit remarkable diversity in their feeding habits. Among them, seven species in the genus Perissodus are known for their unique feeding habit of scale eating with specialized feeding morphology and behaviour. Although the origin of the scale-eating habit has long been questioned, its evolutionary process is still unknown. In the present study, we conducted interspecific phylogenetic analyses for all nine known species in the tribe Perissodini (seven Perissodus and two Haplotaxodon species using amplified fragment length polymorphism (AFLP analyses of the nuclear DNA. On the basis of the resultant phylogenetic frameworks, the evolution of their feeding habits was traced using data from analyses of stomach contents, habitat depths, and observations of oral jaw tooth morphology. Results AFLP analyses resolved the phylogenetic relationships of the Perissodini, strongly supporting monophyly for each species. The character reconstruction of feeding ecology based on the AFLP tree suggested that scale eating evolved from general carnivorous feeding to highly specialized scale eating. Furthermore, scale eating is suggested to have evolved in deepwater habitats in the lake. Oral jaw tooth shape was also estimated to have diverged in step with specialization for scale eating. Conclusion The present evolutionary analyses of feeding ecology and morphology based on the obtained phylogenetic tree demonstrate for the first time the evolutionary process leading from generalised to highly specialized scale eating, with diversification in feeding morphology and behaviour among species.

  8. An alternative approach to determine attainable resolution directly from HREM images

    Wang, A.; Turner, S.; Van Aert, S.; Van Dyck, D.

    2013-01-01

    The concept of resolution in high-resolution electron microscopy (HREM) is the power to resolve neighboring atoms. Since the resolution is related to the width of the point spread function of the microscope, it could in principle be determined from the image of a point object. However, in electron microscopy there are no ideal point objects. The smallest object is an individual atom. If the width of an atom is much smaller than the resolution of the microscope, this atom can still be considered as a point object. As the resolution of the microscope enters the sub-Å regime, information about the microscope is strongly entangled with the information about the atoms in HREM images. Therefore, we need to find an alternative method to determine the resolution in an object-independent way. In this work we propose to use the image wave of a crystalline object in zone axis orientation. Under this condition, the atoms of a column act as small lenses so that the electron beam channels through the atom column periodically. Because of this focusing, the image wave of the column can be much more peaked than the constituting atoms and can thus be a much more sensitive probe to measure the resolution. Our approach is to use the peakiness of the image wave of the atom column to determine the resolution. We will show that the resolution can be directly linked to the total curvature of the atom column wave. Moreover, we can then directly obtain the resolution of the microscope given that the contribution from the object is known, which is related to the bounding energy of the atom. The method is applied on an experimental CaTiO 3 image wave. - Highlights: • Microscope aberrations and the size of the atoms influence the resolution at the sub-Å level. • In channeling condition the atoms in the column focus the electron beam into a narrow peak at the exit face. • The shape of this peak can be used to determine the resolution in an object independent way. • This results in a

  9. Thermoelectric materials -- New directions and approaches. Materials Research Society symposium proceedings, Volume 478

    Tritt, T M; Kanatzidis, M G; Lyon, Jr, H B; Mahan, G D [eds.

    1997-07-01

    Thermoelectric materials are utilized in a wide variety of applications related to solid-state refrigeration or small-scale power generation. Thermoelectric cooling is an environmentally friendly method of small-scale cooling in specific applications such as cooling computer chips and laser diodes. Thermoelectric materials are used in a wide range of applications from beverage coolers to power generation for deep-space probes such as the Voyager missions. Over the past thirty years, alloys based on the Bi-Te systems {l{underscore}brace}(Bi{sub 1{minus}x}Sb{sub x}){sub 2} (Te{sub 1{minus}x}Se{sub x}){sub 3}{r{underscore}brace} and Si{sub 1{minus}x}Ge{sub x} systems have been extensively studied and optimized for their use as thermoelectric materials to perform a variety of solid-state thermoelectric refrigeration and power generation tasks. Despite this extensive investigation of the traditional thermoelectric materials, there is still a substantial need and room for improvement, and thus, entirely new classes of compounds will have to be investigated. Over the past two-to-three years, research in the field of thermoelectric materials has been undergoing a rapid rebirth. The enhanced interest in better thermoelectric materials has been driven by the need for much higher performance and new temperature regimes for thermoelectric devices in many applications. The essence of a good thermoelectric is given by the determination of the material's dimensionless figure of merit, ZT = ({alpha}{sup 2}{sigma}/{lambda})T, where {alpha} is the Seebeck coefficient, {sigma} the electrical conductivity and {lambda} the total thermal conductivity. The best thermoelectric materials have a value of ZT = 1. This ZT = 1 has been an upper limit for more than 30 years, yet no theoretical or thermodynamic reason exits for why it can not be larger. The focus of the symposium is embodied in the title, Thermoelectric Materials: New Directions and Approaches. Many of the researchers in the

  10. The Complex Outgassing of Comets and the Resulting Coma, a Direct Simulation Monte-Carlo Approach

    Fougere, Nicolas

    During its journey, when a comet gets within a few astronomical units of the Sun, solar heating liberates gases and dust from its icy nucleus forming a rarefied cometary atmosphere, the so-called coma. This tenuous atmosphere can expand to distances up to millions of kilometers representing orders of magnitude larger than the nucleus size. Most of the practical cases of coma studies involve the consideration of rarefied gas flows under non-LTE conditions where the hydrodynamics approach is not valid. Then, the use of kinetic methods is required to properly study the physics of the cometary coma. The Direct Simulation Monte-Carlo (DSMC) method is the method of choice to solve the Boltzmann equation, giving the opportunity to study the cometary atmosphere from the inner coma where collisions dominate and is in thermodynamic equilibrium to the outer coma where densities are lower and free flow conditions are verified. While previous studies of the coma used direct sublimation from the nucleus for spherically symmetric 1D models, or 2D models with a day/night asymmetry, recent observations of comets showed the existence of local small source areas such as jets, and extended sources via sublimating icy grains, that must be included into cometary models for a realistic representation of the physics of the coma. In this work, we present, for the first time, 1D, 2D, and 3D models that can take into account the full effects of conditions with more complex sources of gas with jets and/or icy grains. Moreover, an innovative work in a full 3D description of the cometary coma using a kinetic method with a realistic nucleus and outgassing is demonstrated. While most of the physical models used in this study had already been developed, they are included in one self-consistent coma model for the first time. The inclusion of complex cometary outgassing processes represents the state-of-the-art of cometary coma modeling. This provides invaluable information about the coma by

  11. Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

    Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

    2014-01-01

    Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

  12. The evolution of NATO’s comprehensive approach to crisis management operations

    Guillem Colom Piella

    2012-04-01

    Full Text Available The crisis management operations, post-war stabilisation and nation-building that has taken place since the end of the Cold War has all highlighted the extreme need to harmonise multinational and inter-agency cooperation in order to increase the coherence and effectiveness of the operation. That is the basic principle of Comprehensive Approach, which is defined as the coordination of strategies and actions of the participating actors in crisis management and at all levels, stages and planes of same. The NATO has also incorporated these advances into the area of crisis management, as a result of which, since 2006, it has been defining its own concept of Comprehensive Approach for non-Article 5 missions, and as a central theme in its political-military strategy for the present and immediate future.

  13. A Lean Approach to Improving SE Visibility in Large Operational Systems Evolution

    2013-06-01

    engineering activities in such instances. An initial generalization of pull concepts using a standard kanban approach was developed. During the development... Kanban -based Scheduling System (KSS) (Turner, Lane, et al. 2012). The second phase of this research is describing an implementation of the KSS concept...software and systems engineering tasks and the required capabilities. Because kanban concepts have been primarily used with single level value streams

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

    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...

  15. The Evolution of South-South Development Cooperation: Guiding Principles and Approaches

    Bry, Sandra H.

    2017-01-01

    South-South Cooperation (SSC) has attracted the attention of the development community in terms of both its ‘impact’ on traditional aid and the integration of its values into the work of multilateral institutions, making it the new ‘buzzword’ of the aid community. However, few studies have been c...... its geographical component and the other for the guiding principles and approaches of SSDC....

  16. Evolution of floral display in Eichhornia paniculata (Pontederiaceae): direct and correlated responses to selection on flower size and number.

    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.

  17. Evolution of a Lowland Karst Landscape; A Mass-Balance Approach

    Chamberlin, C.; Heffernan, J. B.; Cohen, M. J.; Quintero, C.; Pain, A.

    2016-12-01

    Karst landscapes are highly soluble, and are vulnerable to biological acid production as a major driving factor in their evolution. Big Cypress National Park (BICY) is a low-lying karst landscape in southern Florida displaying a distinctive morphology of isolated depressions likely influenced by biology. The goal of this study is to constrain timescales of landform development in BICY. This question was addressed through the construction of landscape-scale elemental budgets for both calcium and phosphorus. Precipitation and export fluxes were calculated using available chemistry and hydrology data, and stocks were calculated from a combination of existing data, field measurements, and laboratory chemical analysis. Estimates of expected mass export given no biological acid production and given an equivalent production of 100% of GPP were compared with observed rates. Current standing stocks of phosphorus are dominated by a large soil pool, and contain 500 Gg P. Inputs are largely dominated by precipitation, and 8000 years are necessary to accumulate standing stocks of phosphorus given modern fluxes. Calcium flux is vastly dominated by dissolution of the limestone bedrock, and though some calcium is retained in the soil, most is exported. Using LiDAR generated estimates of volume loss across the landscape and current export rates, an estimated 15,000 years would be necessary to create the modern landscape. Both of these estimates indicate that the BICY landscape is geologically very young. The different behaviors of these elements (calcium is largely exported, while phosphorus is largely retained) lend additional confidence to estimates of denudation rates of the landscape. These estimates can be even closer reconciled if calcium redistribution over the landscape is allowed for. This estimate is compared to the two bounding conditions for biological weathering to indicate a likely level of biological importance to landscape development in this system.

  18. Primary health care in rural Malawi - a qualitative assessment exploring the relevance of the community-directed interventions approach

    Makaula, Peter; Bloch, Paul; Banda, Hastings T.

    2012-01-01

    Primary Health Care (PHC) is a strategy endorsed for attaining equitable access to basic health care including treatment and prevention of endemic diseases. Thirty four years later, its implementation remains sub-optimal in most Sub-Saharan African countries that access to health interventions...... is still a major challenge for a large proportion of the rural population. Community-directed treatment with ivermectin (CDTi) and community-directed interventions (CDI) are participatory approaches to strengthen health care at community level. Both approaches are based on values and principles associated...

  19. Risk assessment concept in the new approach directives and its integration in the Enterprise Risk Management (ERM

    Đapić Mirko

    2012-03-01

    Full Text Available In the nineties years of the previous century, the European Union achieved, through introducing the New and Global Approach to technical harmonization and standardization, a significant improvement in the approach to conformity assessment of products, by integrating the requirements for technical products safety into the process of its designing. This was achieved by preventive analyzing and quantifying of risk levels in the design process with the objective of determining the scope of the needed safety systems. On the other hand, we have witnessed a rapid development and implementation of holistic approaches to risks management in enterprises, unified in the modern business practice by the name of Enterprise Risk Management (ERM. Going along that line, the paper presents, through the basis of the EU New and Global Approach, the concept of risk assessment in the New Approach directives (Machinery, Lifts, ATEX, etc and provides the concept of its integration into the holistic approach of risks management in enterprises, such as ERM.

  20. Structures of the Apo and FAD-bound forms of 2-hydroxybiphenyl 3-monooxygenase (HbpA) locate activity hotspots identified by using directed evolution.

    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.

  1. a Statistical Dynamic Approach to Structural Evolution of Complex Capital Market Systems

    Shao, Xiao; Chai, Li H.

    As an important part of modern financial systems, capital market has played a crucial role on diverse social resource allocations and economical exchanges. Beyond traditional models and/or theories based on neoclassical economics, considering capital markets as typical complex open systems, this paper attempts to develop a new approach to overcome some shortcomings of the available researches. By defining the generalized entropy of capital market systems, a theoretical model and nonlinear dynamic equation on the operations of capital market are proposed from statistical dynamic perspectives. The US security market from 1995 to 2001 is then simulated and analyzed as a typical case. Some instructive results are discussed and summarized.

  2. Evolution of a Directional Wave Spectrum in a 3D Marginal Ice Zone with Random Floe Size Distribution

    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

  3. Determination of errors in derived magnetic field directions in geosynchronous orbit: results from a statistical approach

    Chen, Yue; Cunningham, Gregory; Henderson, Michael

    2016-09-01

    This study aims to statistically estimate the errors in local magnetic field directions that are derived from electron directional distributions measured by Los Alamos National Laboratory geosynchronous (LANL GEO) satellites. First, by comparing derived and measured magnetic field directions along the GEO orbit to those calculated from three selected empirical global magnetic field models (including a static Olson and Pfitzer 1977 quiet magnetic field model, a simple dynamic Tsyganenko 1989 model, and a sophisticated dynamic Tsyganenko 2001 storm model), it is shown that the errors in both derived and modeled directions are at least comparable. Second, using a newly developed proxy method as well as comparing results from empirical models, we are able to provide for the first time circumstantial evidence showing that derived magnetic field directions should statistically match the real magnetic directions better, with averaged errors ˜ 5°. In addition, our results suggest that the errors in derived magnetic field directions do not depend much on magnetospheric activity, in contrast to the empirical field models. Finally, as applications of the above conclusions, we show examples of electron pitch angle distributions observed by LANL GEO and also take the derived magnetic field directions as the real ones so as to test the performance of empirical field models along the GEO orbits, with results suggesting dependence on solar cycles as well as satellite locations. This study demonstrates the validity and value of the method that infers local magnetic field directions from particle spin-resolved distributions.

  4. Surgical management of esophageal achalasia: Evolution of an institutional approach to minimally invasive repair.

    Petrosyan, Mikael; Khalafallah, Adham M; Guzzetta, Phillip C; Sandler, Anthony D; Darbari, Anil; Kane, Timothy D

    2016-10-01

    Surgical management of esophageal achalasia (EA) in children has transitioned over the past 2 decades to predominantly involve laparoscopic Heller myotomy (LHM) or minimally invasive surgery (MIS). More recently, peroral endoscopic myotomy (POEM) has been utilized to treat achalasia in children. Since the overall experience with surgical management of EA is contingent upon disease incidence and surgeon experience, the aim of this study is to report a single institutional contemporary experience for outcomes of surgical treatment of EA by LHM and POEM, with regards to other comparable series in children. An IRB approved retrospective review of all patients with EA who underwent treatment by a surgical approach at a tertiary US children's hospital from 2006 to 2015. Data including demographics, operative approach, Eckardt scores pre- and postoperatively, complications, outcomes, and follow-up were analyzed. A total of 33 patients underwent 35 operative procedures to treat achalasia. Of these operations; 25 patients underwent laparoscopic Heller myotomy (LHM) with Dor fundoplication; 4 patients underwent LHM alone; 2 patients underwent LHM with Thal fundoplication; 2 patients underwent primary POEM; 2 patients who had had LHM with Dor fundoplication underwent redo LHM with takedown of Dor fundoplication. Intraoperative complications included 2 mucosal perforations (6%), 1 aspiration, 1 pneumothorax (1 POEM patient). Follow ranged from 8months to 7years (8-84months). There were no deaths and no conversions to open operations. Five patients required intervention after surgical treatment of achalasia for recurrent dysphagia including 3 who underwent between 1 and 3 pneumatic dilations; and 2 who had redo LHM with takedown of Dor fundoplication with all patients achieving complete resolution of symptoms. Esophageal achalasia in children occurs at a much lower incidence than in adults as documented by published series describing the surgical treatment in children. We

  5. A sliding windows approach to analyse the evolution of bank shares in the European Union

    Ferreira, Paulo; Dionísio, Andreia; Guedes, Everaldo Freitas; Zebende, Gilney Figueira

    2018-01-01

    Both sub-prime and Eurozone debt crisis problems caused severe financial crisis, which affected European markets in general, but particularly the banking sector. The continuous devaluation of bank shares in the financial sector caused a great decrease in market capitalization, and in citizen and investor confidence. Panic among investors led them to sell shares, while other agents took the opportunity to buy them. Therefore, the study of bank shares is important, particularly of their efficiency. In this paper, adopting a sliding windows detrended fluctuation approach, we analyse the efficiency concept dynamically with 63 European banks (both in and outside the Eurozone). The main results show that the crisis had an effect on changing the efficiency pattern.

  6. Aging as Evolution-Facilitating Program and a Biochemical Approach to Switch It Off

    Skulachev, Vladimir P.

    A concept is presented considering aging of living organisms as a final step of their ontogenetic program. It is assumed that such an aging program was invented by biological evolution to facilitate the evolutionary process. Indications are summarized suggesting that controlled production of toxic forms of oxygen (so called reactive oxygen species) by respiring intracellular organelles (mitochondria) is an obligatory component of the aging program. First results of a research project devoted to an attempt to interrupt aging program by antioxidants specifically addressed to mitochondria have been described. Within the framework of the project, antioxidants of a new type (SkQ) were synthesized. SkQs are composed of (i) plastoquinone (an antioxidant moiety), (ii) a penetrating cation, and (iii) a decane or pentane linker. Using planar bilayer phospholipid membranes, we selected SkQ derivatives of the highest penetrability, namely plastoquinonyl decyl triphenylphosphonium (SkQ1), plastoquinonyl decyl rhodamine 19 (SkQR1), and methylplastoquinonyl decyl triphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in isolated mitochondria. Micromolar concentrations of cationic quinones are found to be very strong prooxidants, but in the lower (sub-micromolar) concentrations they display antioxidant activity which decreases in the series SkQ1 = SkQR1 > SkQ3 > MitoQ. Thus, the window between the anti- and prooxidant effects is the smallest for MitoQ and the largest for SkQ1 and SkQR1. SkQ1 is rapidly reduced by complex III of the mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Extremely low concentrations of SkQ1 and SkQR1 completely arrest the H2O2-induced apoptosis in human fibroblasts and HeLa cells (for SkQ1, C 1/2 = 8 · 10-9M). Higher concentrations of SkQ1 are required to block necrosis initiated by reactive oxygen species (ROS). In mice, SkQ1

  7. On a direct approach to quasideterminant solutions of a noncommutative modified KP equation

    Gilson, C R; Nimmo, J J C; Sooman, C M

    2008-01-01

    A noncommutative version of the modified KP equation and a family of its solutions expressed as quasideterminants are discussed. The origin of these solutions is explained by means of Darboux transformations and the solutions are verified directly. We also verify directly an explicit connection between quasideterminant solutions of the noncommutative mKP equation and the noncommutative KP equation arising from the Miura transformation

  8. A Contingency Approach to Communication Skill Importance: The Impact of Occupation, Direction, and Position.

    Di Salvo, Vincent S.; Larsen, Janet K.

    1987-01-01

    Examines the impact of direction and occupation on the importance of communication skills for entry-level positions in finance, management, engineering, and law. Results substantiate a three-dimensional model (based on direction, occupation, and position) for the examination and application of communication skill importance in organization. (JD)

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

    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...

  10. Segregation and microstructure evolution in chill cast and directionally solidified Ni-Mn-Sn metamagnetic shape memory alloys

    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.

  11. A dynamic monitoring approach for the surface morphology evolution measurement of plasma facing components by means of speckle interferometry

    Wang, Hongbei; Cui, Xiaoqian; Feng, Chunlei; Li, Yuanbo; Zhao, Mengge; Luo, Guangnan; Ding, Hongbin

    2017-11-01

    Plasma Facing Components (PFCs) in a magnetically confined fusion plasma device will be exposed to high heat load and particle fluxes, and it would cause PFCs' surface morphology to change due to material erosion and redeposition from plasma wall interactions. The state of PFCs' surface condition will seriously affect the performance of long-pulse or steady state plasma discharge in a tokamak; it will even constitute an enormous threat to the operation and the safety of fusion plasma devices. The PFCs' surface morphology evolution measurement could provide important information about PFCs' real-time status or damage situation and it would help to a better understanding of the plasma wall interaction process and mechanism. Meanwhile through monitoring the distribution of dust deposition in a tokamak and providing an upper limit on the amount of loose dust, the PFCs' surface morphology measurement could indirectly contribute to keep fusion operational limits and fusion device safety. Aiming at in situ dynamic monitoring PFCs' surface morphology evolution, a laboratory experimental platform DUT-SIEP (Dalian University of Technology-speckle interferometry experimental platform) based on the speckle interferometry technique has been constructed at Dalian University of Technology (DUT) in China. With directional specific designing and focusing on the real detection condition of EAST (Experimental Advanced Superconducting Tokamak), the DUT-SIEP could realize a variable measurement range, widely increased from 0.1 μm to 300 μm, with high spatial resolution (<1 mm) and ultra-high time resolution (<2 s for EAST measuring conditions). Three main components of the DUT-SIEP are all integrated and synchronized by a time schedule control and data acquisition terminal and coupled with a three-dimensional phase unwrapping algorithm, the surface morphology information of target samples can be obtained and reconstructed in real-time. A local surface morphology of the real divertor

  12. Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers

    den Uyl, T.E.; Gladwin, T.E.; Wiers, R.W.

    2016-01-01

    BACKGROUND: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying

  13. One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections

    Mingo, J.; Erramuzpe, A.; Luna, S.; Aurtenetxe, O.; Amo, L.; Diez, I.; Schepens, J.T.G.; Hendriks, W.J.A.J.; Cortes, J.M.; Pulido, R.

    2016-01-01

    Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates

  14. The surgical anatomy of the superior gluteal nerve and anatomical radiologic bases of the direct lateral approach to the hip

    J.C. Bos (Jan); R. Stoeckart (Rob); A. Klooswijk (Aij); B. van Linge (Bert); R. Bahadoer (R.)

    1994-01-01

    textabstractIn view of the increasing popularity of the direct lateral approach to the hip joint for hemi- or total hip arthroplasty, the location of the superior gluteal nerve (SGN) was studied. This nerve is in danger when using a transgluteal incision. In 20 embalmed specimens the relation of the

  15. A Modern Approach to Disinfection, as Old as the Evolution of Vertebrates

    Franco Migliarina

    2014-12-01

    Full Text Available The immune system of vertebrates “naturally” produces hypochlorous acid (HOCl to fight against bacteria and pathogens. A patented electrochemical technology mirrors the above defense system, allowing the synthesis of HOCl solutions through the electrolysis of water enriched in salts, at the level of a few grams per liter. The system allows for the careful control of the pH of produced solutions, with consequent optimization of their activity. Once the HOCl is introduced into the water system; it is able to remove the biofilm from pipe network; significantly decreasing the level of Legionella colonization; within 8–10 weeks from the beginning of the disinfection approach. The technology has been applied in a variety of healthcare facilities, both in Italy and in neighboring European countries. In the present paper, two successful case studies are briefly presented: Data were obtained from experiences in two different healthcare facilities, one in Italy and the other in Germany. Destruction of biofilm was indirectly testified by an increase of total organic carbon content of water; as a consequence, and because of the dosing of the disinfecting agent, some μg/L of total halomethanes were also formed. However, both compositional features were only observed during the initial stages of the disinfection treatment.

  16. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

    Masson, Patrick

    2011-09-25

    After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Establishing a multi-proxy approach to alpine blockfield evolution in south-central Norway

    Philipp Marr

    2017-11-01

    Full Text Available Blockfields in high latitude mountain areas are a wide spread proxy for glaciation history. Their origin is debated since decades, especially in south-central Norway, where glaciation had a major global climate implication. Some authors explain old blockfield features by protection of cold-based ice, others claim they persisted as nunataks during the LGM (~20 kyr, or were formed throughout the Holocene. In order to clarify the origin of alpine blockfields we established a multi-method approach to combining lichenometry, stratigraphy, granulometry, and geochemistry (XRD, XRF. Our lichenometric dating results in conjunction with our factors indicate landscape stability for at least ~12.5 kyr. Frequent climatic shifts are evident in our profiles by varying color, LOI content and grain sizes. On the basis of geochemical analyses we were able to identify a long-term (chemical weathering history and in situ blockfield formation. The field evidences and the climatic setting of the study area leave the possibility that our location was not covered by cold-based ice during the Late-Quaternary.

  18. Arbitrarily amplified DNA: New molecular approaches to plant breeding, ecology and evolution

    Caetano-Anolles, G [Department of Biology, University of Oslo, Oslo (Norway)

    2001-11-01

    Several DNA fingerprinting techniques that use arbitrary primers to characterize, scan and tag genomic DNA were optimized and used to study plants and microbial pathogens. The generated arbitrarily amplified DNA (AAD) profiles could be tailored in their complexity and polymorphic content, allowing analysis of closely related organisms, such as vegetatively-propagated horticultural crops or clonal fungal populations. AAD markers were used in cultivar and strain identification, map-based cloning, and marker-assisted breeding, sometimes as sequence-tagged sites. Phenetic analysis using parsimony, cluster, and numerical methods was applied successfully to the identification of genetic relationships in turfgrass species such as bermudagrass, woody plants such as dogwoods, and floricultural species such as petunia and chrysanthemum. AAD profiles were used to measure for the first time a genome-wide mutation rate, directly in a plant. Mutation rates in vegetatively propagated bermudagrass were comparable to those in human, mice, fruit flies, and worms. In combination with established tools used in molecular systematics (e.g. rDNA sequence analysis), AAD markers tracked the introduction of exotic dogwood anthracnose-causing fungi in North America. As part of a breeding effort to combat dogwood diseases, AAD was used in pseudo-testcross mapping of the tree at the intra-specific level. Markers were efficiently generated despite the close relatedness of parental dogwood material. Finally, DNA markers and tags were also generated in soybean, and were used to construct high density maps and walk towards defined genomic regions in the positional cloning of the supernodulation nts-1 symbiotic gene. (author)

  19. Arbitrarily amplified DNA: New molecular approaches to plant breeding, ecology and evolution

    Caetano-Anolles, G.

    2001-01-01

    Several DNA fingerprinting techniques that use arbitrary primers to characterize, scan and tag genomic DNA were optimized and used to study plants and microbial pathogens. The generated arbitrarily amplified DNA (AAD) profiles could be tailored in their complexity and polymorphic content, allowing analysis of closely related organisms, such as vegetatively-propagated horticultural crops or clonal fungal populations. AAD markers were used in cultivar and strain identification, map-based cloning, and marker-assisted breeding, sometimes as sequence-tagged sites. Phenetic analysis using parsimony, cluster, and numerical methods was applied successfully to the identification of genetic relationships in turfgrass species such as bermudagrass, woody plants such as dogwoods, and floricultural species such as petunia and chrysanthemum. AAD profiles were used to measure for the first time a genome-wide mutation rate, directly in a plant. Mutation rates in vegetatively propagated bermudagrass were comparable to those in human, mice, fruit flies, and worms. In combination with established tools used in molecular systematics (e.g. rDNA sequence analysis), AAD markers tracked the introduction of exotic dogwood anthracnose-causing fungi in North America. As part of a breeding effort to combat dogwood diseases, AAD was used in pseudo-testcross mapping of the tree at the intra-specific level. Markers were efficiently generated despite the close relatedness of parental dogwood material. Finally, DNA markers and tags were also generated in soybean, and were used to construct high density maps and walk towards defined genomic regions in the positional cloning of the supernodulation nts-1 symbiotic gene. (author)

  20. Radiological and acetomorphine analysis of the symmetry and direction of evolution of skulls from some historic populations

    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

  1. The Evolution of Cooperation in Managed Groundwater Systems: An Agent-Based Modelling Approach

    Castilla Rho, J. C.; Mariethoz, G.; Rojas, R. F.; Andersen, M. S.; Kelly, B. F.; Holley, C.

    2014-12-01

    Human interactions with groundwater systems often exhibit complex features that hinder the sustainable management of the resource. This leads to costly and persistent conflicts over groundwater at the catchment scale. One possible way to address these conflicts is by gaining a better understanding of how social and groundwater dynamics coevolve using agent-based models (ABM). Such models allow exploring 'bottom-up' solutions (i.e., self-organised governance systems), where the behaviour of individual agents (e.g., farmers) results in the emergence of mutual cooperation among groundwater users. There is significant empirical evidence indicating that this kind of 'bottom-up' approach may lead to more enduring and sustainable outcomes, compared to conventional 'top-down' strategies such as centralized control and water right schemes (Ostrom 1990). New modelling tools are needed to study these concepts systematically and efficiently. Our model uses a conceptual framework to study cooperation and the emergence of social norms as initially proposed by Axelrod (1986), which we adapted to groundwater management. We developed an ABM that integrates social mechanisms and the physics of subsurface flow. The model explicitly represents feedback between groundwater conditions and social dynamics, capturing the spatial structure of these interactions and the potential effects on cooperation levels in an agricultural setting. Using this model, we investigate a series of mechanisms that may trigger norms supporting cooperative strategies, which can be sustained and become stable over time. For example, farmers in a self-monitoring community can be more efficient at achieving the objective of sustainable groundwater use than government-imposed regulation. Our coupled model thus offers a platform for testing new schemes promoting cooperation and improved resource use, which can be used as a basis for policy design. Importantly, we hope to raise awareness of agent-based modelling as

  2. Clarkson-Kruskal Direct Similarity Approach for Differential-Difference Equations

    SHEN Shou-Feng

    2005-01-01

    In this letter, the Clarkson-Kruskal direct method is extended to similarity reduce some differentialdifference equations. As examples, the differential-difference KZ equation and KP equation are considered.

  3. Policy directions in urban health in developing countries--the slum improvement approach.

    Harpham, T; Stephens, C

    1992-07-01

    The urban development, or housing, sector has a longer experience of addressing the problems of the urban poor in developing countries than the health sector. In recent years the policy of 'slum improvement', which involves both sectors, has attracted the support of international donors. This article documents the development of the slum improvement approach and addresses key issues of the approach which have implications for health planning: covering the poorest dwellers; relocation; land tenure; gentrification; debt burdens and the impact on women. Questions about the approach which still need answering are defined and a summary of the constraints in slum improvement and potential solutions is presented.

  4. Direct energy rebound effect for road passenger transport in China: A dynamic panel quantile regression approach

    Zhang, Yue-Jun; Peng, Hua-Rong; Liu, Zhao; Tan, Weiping

    2015-01-01

    The transport sector appears a main energy consumer in China and plays a significant role in energy conservation. Improving energy efficiency proves an effective way to reduce energy consumption in transport sector, whereas its effectiveness may be affected by the rebound effect. This paper proposes a dynamic panel quantile regression model to estimate the direct energy rebound effect for road passenger transport in the whole country, eastern, central and western China, respectively, based on the data of 30 provinces from 2003 to 2012. The empirical results reveal that, first of all, the direct rebound effect does exist for road passenger transport and on the whole country, the short-term and long-term direct rebound effects are 25.53% and 26.56% on average, respectively. Second, the direct rebound effect for road passenger transport in central and eastern China tends to decrease, increase and then decrease again, whereas that in western China decreases and then increases, with the increasing passenger kilometers. Finally, when implementing energy efficiency policy in road passenger transport sector, the effectiveness of energy conservation in western China proves much better than that in central China overall, while the effectiveness in central China is relatively better than that in eastern China. - Highlights: • The direct rebound effect (RE) for road passenger transport in China is estimated. • The direct RE in the whole country, eastern, central, and western China is analyzed. • The short and long-term direct REs are 25.53% and 26.56% within the sample period. • Western China has better energy-saving performance than central and eastern China.

  5. Analysis of Fundus Fluorescein Angiogram Based on the Hessian Matrix of Directional Curvelet Sub-bands and Distance Regularized Level Set Evolution.

    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.

  6. Critical dialogical approach: A methodological direction for occupation-based social transformative work.

    Farias, Lisette; Laliberte Rudman, Debbie; Pollard, Nick; Schiller, Sandra; Serrata Malfitano, Ana Paula; Thomas, Kerry; van Bruggen, Hanneke

    2018-05-03

    Calls for embracing the potential and responsibility of occupational therapy to address socio-political conditions that perpetuate occupational injustices have materialized in the literature. However, to reach beyond traditional frameworks informing practices, this social agenda requires the incorporation of diverse epistemological and methodological approaches to support action commensurate with social transformative goals. Our intent is to present a methodological approach that can help extend the ways of thinking or frameworks used in occupational therapy and science to support the ongoing development of practices with and for individuals and collectives affected by marginalizing conditions. We describe the epistemological and theoretical underpinnings of a methodological approach drawing on Freire and Bakhtin's work. Integrating our shared experience taking part in an example study, we discuss the unique advantages of co-generating data using two methods aligned with this approach; dialogical interviews and critical reflexivity. Key considerations when employing this approach are presented, based on its proposed epistemological and theoretical stance and our shared experiences engaging in it. A critical dialogical approach offers one way forward in expanding occupational therapy and science scholarship by promoting collaborative knowledge generation and examination of taken-for-granted understandings that shape individuals assumptions and actions.

  7. Approaches for the direct estimation of lambda, and demographic contributions to lambda, using capture-recapture data

    Nichols, James D.; Hines, James E.

    2002-01-01

    We first consider the estimation of the finite rate of population increase or population growth rate, u i , using capture-recapture data from open populations. We review estimation and modelling of u i under three main approaches to modelling openpopulation data: the classic approach of Jolly (1965) and Seber (1965), the superpopulation approach of Crosbie & Manly (1985) and Schwarz & Arnason (1996), and the temporal symmetry approach of Pradel (1996). Next, we consider the contributions of different demographic components to u i using a probabilistic approach based on the composition of the population at time i + 1 (Nichols et al., 2000b). The parameters of interest are identical to the seniority parameters, n i , of Pradel (1996). We review estimation of n i under the classic, superpopulation, and temporal symmetry approaches. We then compare these direct estimation approaches for u i and n i with analogues computed using projection matrix asymptotics. We also discuss various extensions of the estimation approaches to multistate applications and to joint likelihoods involving multiple data types.

  8. Desarrollo de biocatalizadores hidrofóbicos y termotolerantes mediante técnicas de evolución dirigida Development of hydrofobic and thermotolerant biocatalysts by directed evolution techniques

    Mogollón G. Leonardo Ivan

    2002-06-01

    Full Text Available

    La evolución dirigida se presenta hoy como una de las alternativas más efectivas en el desarrollo y adaptación de biocatalizadores a los requerimientos industriales. Este trabajo muestra el desarrollo de biocatalizadores más hidrofóbicos y termotolerantes útiles en procesos de biorefinación. Para la Industria del Petróleo. Se presenta la obtención de una segunda librería del gen de la enzima Cloroperoxidasa por Error-Prone PCR (EP-PCR y la selección de los mejores mutantes de acuerdo con el grado de hidrofobicidad, termorresistencia y estabilidad en medios orgánicos. Estas proteínas fueron más activas que las obtenidas en la primera librería y que la proteína nativa. Se demuestra que esta técnica de evolución dirigida es eficiente en la generación de variedades enzimáticas de interés industrial.

    Directed evolution has emerged as one of the most effective approaches in developing and adapting biocatalysts to industrial requirements. This work shows the development of hidrophobic and thermotolerant biocatalyst useful in biorefining processes for the Petroleum Industry. We generated a second library of Cloroperoxidase enzyme gene by Error-Prone PCR (EP-PCR with the selection of the best mutants based on their hidrophobicity, thermoresistance and stability in organic media. These proteins were more active than the first library mutants and the wildtype enzyme. We demonstrated that this directed evolution technique is efficient in generating chimeric libraries of enzymes of industrial interest. 

  9. Direct ophthalmoscopy on YouTube: analysis of instructional YouTube videos' content and approach to visualization.

    Borgersen, Nanna Jo; Henriksen, Mikael Johannes Vuokko; Konge, Lars; Sørensen, Torben Lykke; Thomsen, Ann Sofia Skou; Subhi, Yousif

    2016-01-01

    Direct ophthalmoscopy is well-suited for video-based instruction, particularly if the videos enable the student to see what the examiner sees when performing direct ophthalmoscopy. We evaluated the pedagogical effectiveness of instructional YouTube videos on direct ophthalmoscopy by evaluating their content and approach to visualization. In order to synthesize main themes and points for direct ophthalmoscopy, we formed a broad panel consisting of a medical student, junior and senior physicians, and took into consideration book chapters targeting medical students and physicians in general. We then systematically searched YouTube. Two authors reviewed eligible videos to assess eligibility and extract data on video statistics, content, and approach to visualization. Correlations between video statistics and contents were investigated using two-tailed Spearman's correlation. We screened 7,640 videos, of which 27 were found eligible for this study. Overall, a median of 12 out of 18 points (interquartile range: 8-14 key points) were covered; no videos covered all of the 18 points assessed. We found the most difficulties in the approach to visualization of how to approach the patient and how to examine the fundus. Time spent on fundus examination correlated with the number of views per week (Spearman's ρ=0.53; P=0.029). Videos may help overcome the pedagogical issues in teaching direct ophthalmoscopy; however, the few available videos on YouTube fail to address this particular issue adequately. There is a need for high-quality videos that include relevant points, provide realistic visualization of the examiner's view, and give particular emphasis on fundus examination.

  10. Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

    Dong, Zheng; Zhou, Hongyu; Tao, Peng

    2018-02-01

    PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

  11. ScienceDirect through SciVerse: a new way to approach Elsevier.

    Bengtson, Jason

    2011-01-01

    SciVerse is the new combined portal from Elsevier that services their ScienceDirect collection, SciTopics, and their Scopus database. Using SciVerse to access ScienceDirect is the specific focus of this review. Along with advanced keyword searching and citation searching options, SciVerse also incorporates a very useful image search feature. The aim seems to be not only to create an interface that provides broad functionality on par with other database search tools that many searchers use regularly but also to create an open platform that could be changed to respond effectively to the needs of customers.

  12. The directive establishing a community framework for the nuclear safety of nuclear installations: the European Union approach to nuclear safety

    Garribba, M.; Chirtes, A.; Nauduzaite, M.

    2009-01-01

    This article aims at explaining the evolution leading to the adoption of the recent Council Directive 2009/71/EURATOM establishing a Community framework for the nuclear safety of nuclear installations adopted with the consent of all 27 members states following the overwhelming support of the European Parliament, that creates for the first time, a binding legal framework that brings legal certainty to European Union citizens and reinforces the role and independence of national regulators. The paper is divided into three sections. The first section addresses the competence of the European Atomic energy Community to legislate in the area of nuclear safety. It focuses on the 2002 landmark ruling of the European Court of justice that confirmed this competence by recognizing the intrinsic link between radiation protection and nuclear safety. The second part describes the history of the Nuclear safety directive from the initial 2003 European Commission proposal to today 's text in force. The third part is dedicated to a description of the content of the Directive and its implications on the further development of nuclear safety in the European Union. (N.C.)

  13. Direct view on the phase evolution in individual LiFePO4 nanoparticles during Li-ion battery cycling.

    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.

  14. The evolution of peer review as a basis for scientific publication: directional selection towards a robust discipline?

    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. An Approach to Dynamic Line Rating State Estimation at Steady State Using Direct and Indirect Measurements

    Alvarez, David; Silva, Filipe Miguel Faria da; Mombello, Enrique E.

    2018-01-01

    Dynamic line rating has emerged as a solution for reducing congestion in overhead lines, allowing the optimization of power systems assets. This technique is based on direct and/or indirect monitoring of conductor temperature. Different devices and methods have been developed to sense conductor...

  16. Direction of coupling from phases of interacting oscillators: An information-theoretic approach

    Paluš, Milan; Stefanovska, Aneta

    2003-05-01

    A directionality index based on conditional mutual information is proposed for application to the instantaneous phases of weakly coupled oscillators. Its abilities to distinguish unidirectional from bidirectional coupling, as well as to reveal and quantify asymmetry in bidirectional coupling, are demonstrated using numerical examples of quasiperiodic, chaotic, and noisy oscillators, as well as real human cardiorespiratory data.

  17. Direct Determination of Absolute Configuration of Methyl-Substituted Phenyloxiranes: A Combined Experimental and Theoretical Approach

    Fristrup, Peter; Lassen, Peter Rygaard; Johannessen, Christian

    2006-01-01

    obtained from quantum mechanical calculations (density functional theory with the B3LYP hybrid exchange correlation functional with 6-31++G**, aug-cc-pVDZ, or aug-cc-pVTZ basis set) and related to the physical structure of the compounds. The absolute configuration could be established directly in each case...

  18. Oscillatory mechanisms of response conflict elicited by color and motion direction: : an individual differences approach

    Vissers, M.E.; Ridderinkhof, K.R.; Cohen, M.X.; Slagter, H.A.

    Goal-directed behavior requires control over automatic behavior, for example, when goal-irrelevant information from the environment captures an inappropriate response and conflicts with the correct, goal-relevant action. Neural oscillations in the theta band (∼6 Hz) measured at midfrontal electrodes

  19. Using a Combined Approach of Guided Inquiry & Direct Instruction to Explore How Physiology Affects Behavior

    Machtinger, Erika T.

    2014-01-01

    Hands-on activities with live organisms allow students to actively explore scientific investigation. Here, I present activities that combine guided inquiry with direct instruction and relate how nutrition affects the physiology and behavior of the common housefly. These experiments encourage student involvement in the formulation of experimental…

  20. Development of a Supported Self-Directed Learning Approach for Anatomy Education

    Findlater, Gordon S.; Kristmundsdottir, Fanney; Parson, Simon H.; Gillingwater, Thomas H.

    2012-01-01

    The ability to deliver sufficient core anatomical knowledge and understanding to medical students with limited time and resources remains a major challenge for anatomy educators. Here, we report the results of switching from a primarily didactic method of teaching to supported self-directed learning for students studying anatomy as part of…

  1. The spatial turn and the scenario approach in flood risk management—Implementing the European Floods Directive in the Netherlands

    Leon J. van Ruiten

    2016-10-01

    Full Text Available The European Floods Directive requires member states to prepare flood risk management plans for their river catchments. The first generation of those plans was just developed at the end of 2015; the next revision is due in 2021. The new instrument institutionalizes an ongoing paradigm shift from flood protection to flood risk management in Europe. It implies two major governance challenges: the spatial turn and the scenario approach. This contribution studies the implementation of these two governance challenges in the Netherlands, where the paradigm shift is considered to be advanced. Therefore, the spatial turn and the scenario approach are operationalized. The spatial turn consists of three aspects: space for the river, an integrated approach, and beyond structural measures. The scenario approach introduces the vulnerability of society in flood risk management. It is discussed how the challenges of spatial turn and the scenario approach—and thus the shift towards flood risk management—have an effect on the prevailing modes of governance in water management in the Netherlands. This helps understand the tensions and frictions with implementing the plans, but also illustrates how the European Floods Directive institutionalizes the shift towards flood risk management. The analytical scheme, consists mainly of operationalization, can foster future comparative studies with other countries and over time, to trace the changes in approaches to flood risks in Europe.

  2. Development of a state machine sequencer for the Keck Interferometer: evolution, development, and lessons learned using a CASE tool approach

    Reder, Leonard J.; Booth, Andrew; Hsieh, Jonathan; Summers, Kellee R.

    2004-09-01

    This paper presents a discussion of the evolution of a sequencer from a simple Experimental Physics and Industrial Control System (EPICS) based sequencer into a complex implementation designed utilizing UML (Unified Modeling Language) methodologies and a Computer Aided Software Engineering (CASE) tool approach. The main purpose of the Interferometer Sequencer (called the IF Sequencer) is to provide overall control of the Keck Interferometer to enable science operations to be carried out by a single operator (and/or observer). The interferometer links the two 10m telescopes of the W. M. Keck Observatory at Mauna Kea, Hawaii. The IF Sequencer is a high-level, multi-threaded, Harel finite state machine software program designed to orchestrate several lower-level hardware and software hard real-time subsystems that must perform their work in a specific and sequential order. The sequencing need not be done in hard real-time. Each state machine thread commands either a high-speed real-time multiple mode embedded controller via CORBA, or slower controllers via EPICS Channel Access interfaces. The overall operation of the system is simplified by the automation. The UML is discussed and our use of it to implement the sequencer is presented. The decision to use the Rhapsody product as our CASE tool is explained and reflected upon. Most importantly, a section on lessons learned is presented and the difficulty of integrating CASE tool automatically generated C++ code into a large control system consisting of multiple infrastructures is presented.

  3. Evolution of flavone synthase I from parsley flavanone 3beta-hydroxylase by site-directed mutagenesis.

    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).

  4. Enzyme (re)design: lessons from natural evolution and computation.

    Gerlt, John A; Babbitt, Patricia C

    2009-02-01

    The (re)design of enzymes to catalyze 'new' reactions is a topic of considerable practical and intellectual interest. Directed evolution (random mutagenesis followed by screening/selection) has been used widely to identify novel biocatalysts. However, 'rational' approaches using either natural divergent evolution or computational predictions based on chemical principles have been less successful. This review summarizes recent progress in evolution-based and computation-based (re)design.

  5. The Pedagogical Orientations of South African Physical Sciences Teachers towards Inquiry or Direct Instructional Approaches

    Ramnarain, Umesh; Schuster, David

    2014-01-01

    In recent years, inquiry-based science instruction has become widely advocated in science education standards in many countries and, hence, in teacher preparation programmes. Nevertheless, in practice, one finds a wide variety of science instructional approaches. In South Africa, as in many countries, there is also a great disparity in school…

  6. Rapid approach for cloning bacterial single-genes directly from soils ...

    Obtaining functional genes of bacteria from environmental samples usually depends on library-based approach which is not favored as its large amount of work with small possibility of positive clones. A kind of bacterial single-gene encoding glutamine synthetase (GS) was selected as example to detect the efficiency of ...

  7. Show Me the Way: Future Faculty Prefer Directive Feedback When Trying Active Learning Approaches

    Stephens, Jessica D.; Battle, David C.; Gormally, Cara L.; Brickman, Peggy

    2017-01-01

    Early training opportunities for future faculty, namely graduate students and postdoctoral researchers, can better prepare them to use active learning approaches. We know that instructional feedback supports sustained change and motivates instructors to improve teaching practices. Here, we incorporate feedback as a key component of a pedagogical…

  8. A Comparison of Three Approaches to Correct for Direct and Indirect Range Restrictions: A Simulation Study

    Pfaffel, Andreas; Schober, Barbara; Spiel, Christiane

    2016-01-01

    A common methodological problem in the evaluation of the predictive validity of selection methods, e.g. in educational and employment selection, is that the correlation between predictor and criterion is biased. Thorndike's (1949) formulas are commonly used to correct for this biased correlation. An alternative approach is to view the selection…

  9. Initial Comparison of Direct and Legacy Modeling Approaches for Radial Core Expansion Analysis

    Shemon, Emily R.

    2016-01-01

    Radial core expansion in sodium-cooled fast reactors provides an important reactivity feedback effect. As the reactor power increases due to normal start up conditions or accident scenarios, the core and surrounding materials heat up, causing both grid plate expansion and bowing of the assembly ducts. When the core restraint system is designed correctly, the resulting structural deformations introduce negative reactivity which decreases the reactor power. Historically, an indirect procedure has been used to estimate the reactivity feedback due to structural deformation which relies upon perturbation theory and coupling legacy physics codes with limited geometry capabilities. With advancements in modeling and simulation, radial core expansion phenomena can now be modeled directly, providing an assessment of the accuracy of the reactivity feedback coefficients generated by indirect legacy methods. Recently a new capability was added to the PROTEUS-SN unstructured geometry neutron transport solver to analyze deformed meshes quickly and directly. By supplying the deformed mesh in addition to the base configuration input files, PROTEUS-SN automatically processes material adjustments including calculation of region densities to conserve mass, calculation of isotopic densities according to material models (for example, sodium density as a function of temperature), and subsequent re-homogenization of materials. To verify the new capability of directly simulating deformed meshes, PROTEUS-SN was used to compute reactivity feedback for a series of contrived yet representative deformed configurations for the Advanced Burner Test Reactor design. The indirect legacy procedure was also performed to generate reactivity feedback coefficients for the same deformed configurations. Interestingly, the legacy procedure consistently overestimated reactivity feedbacks by 35% compared to direct simulations by PROTEUS-SN. This overestimation indicates that the legacy procedures are in fact

  10. Initial Comparison of Direct and Legacy Modeling Approaches for Radial Core Expansion Analysis

    Shemon, Emily R. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-10-10

    Radial core expansion in sodium-cooled fast reactors provides an important reactivity feedback effect. As the reactor power increases due to normal start up conditions or accident scenarios, the core and surrounding materials heat up, causing both grid plate expansion and bowing of the assembly ducts. When the core restraint system is designed correctly, the resulting structural deformations introduce negative reactivity which decreases the reactor power. Historically, an indirect procedure has been used to estimate the reactivity feedback due to structural deformation which relies upon perturbation theory and coupling legacy physics codes with limited geometry capabilities. With advancements in modeling and simulation, radial core expansion phenomena can now be modeled directly, providing an assessment of the accuracy of the reactivity feedback coefficients generated by indirect legacy methods. Recently a new capability was added to the PROTEUS-SN unstructured geometry neutron transport solver to analyze deformed meshes quickly and directly. By supplying the deformed mesh in addition to the base configuration input files, PROTEUS-SN automatically processes material adjustments including calculation of region densities to conserve mass, calculation of isotopic densities according to material models (for example, sodium density as a function of temperature), and subsequent re-homogenization of materials. To verify the new capability of directly simulating deformed meshes, PROTEUS-SN was used to compute reactivity feedback for a series of contrived yet representative deformed configurations for the Advanced Burner Test Reactor design. The indirect legacy procedure was also performed to generate reactivity feedback coefficients for the same deformed configurations. Interestingly, the legacy procedure consistently overestimated reactivity feedbacks by 35% compared to direct simulations by PROTEUS-SN. This overestimation indicates that the legacy procedures are in fact

  11. Direct Measurements of the Evolution and Impact of Sediment Density Flows as they Pass Through Monterey Submarine Canyon, Offshore California

    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

  12. Cellular Spacing Selection During the Directional Solidification of Binary Alloys. A Numerical Approach

    Catalina, Adrian V.; Sen, S.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    The evolution of cellular solid/liquid interfaces from an initially unstable planar front was studied by means of a two-dimensional computer simulation. The developed numerical model makes use of an interface tracking procedure and has the capability to describe the dynamics of the interface morphology based on local changes of the thermodynamic conditions. The fundamental physics of this formulation was validated against experimental microgravity results and the predictions of the analytical linear stability theory. The performed simulations revealed that in certain conditions, based on a competitive growth mechanism, an interface could become unstable to random perturbations of infinitesimal amplitude even at wavelengths smaller than the neutral wavelength, lambda(sub c), predicted by the linear stability theory. Furthermore, two main stages of spacing selection have been identified. In the first stage, at low perturbations amplitude, the selection mechanism is driven by the maximum growth rate of instabilities while in the second stage the selection is influenced by nonlinear phenomena caused by the interactions between the neighboring cells. Comparison of these predictions with other existing theories of pattern formation and experimental results will be discussed.

  13. A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli.

    Angeliki Theodoridou

    Full Text Available Oxytocin has been shown to promote a host of social behaviors in humans but the exact mechanisms by which it exerts its effects are unspecified. One prominent theory suggests that oxytocin increases approach and decreases avoidance to social stimuli. Another dominant theory posits that oxytocin increases the salience of social stimuli. Herein, we report a direct test of these hypotheses. In a double-blind, placebo-controlled study we examined approach-avoidance motor responses to social and non-social emotional stimuli. One hundred and twenty participants self-administered either 24 IU oxytocin or placebo and moved a lever toward or away from pictures of faces depicting emotional expressions or from natural scenes appearing before them on a computer screen. Lever movements toward stimuli decreased and movements away increased stimuli size producing the illusion that stimuli moved away from or approached participants. Reaction time data were recorded. The task produced the effects that were anticipated on the basis of the approach-avoidance literature in relation to emotional stimuli, yet the anticipated speeded approach and slowed avoidance responses to emotional faces by the oxytocin group were not observed. Interestingly, the oxytocin treatment group was faster to approach and avoid faces depicting disgust relative to the placebo group, suggesting a salience of disgust for the former group. Results also showed that within the oxytocin group women's reaction times to all emotional faces were faster than those of men, suggesting sex specific effects of oxytocin. The present findings provide the first direct evidence that intranasal oxytocin administration does not enhance approach/avoidance to social stimuli and does not exert a stronger effect on social vs. non-social stimuli in the context of processing of emotional expressions and scenes. Instead, our data suggest that oxytocin administration increases the salience of certain social stimuli

  14. On Direct Transformation Approach to Asymptotical Analytical Solutions of Perturbed Partial Differential Equation

    Liu Hongzhun; Pan Zuliang; Li Peng

    2006-01-01

    In this article, we will derive an equality, where the Taylor series expansion around ε = 0 for any asymptotical analytical solution of the perturbed partial differential equation (PDE) with perturbing parameter ε must be admitted. By making use of the equality, we may obtain a transformation, which directly map the analytical solutions of a given unperturbed PDE to the asymptotical analytical solutions of the corresponding perturbed one. The notion of Lie-Baecklund symmetries is introduced in order to obtain more transformations. Hence, we can directly create more transformations in virtue of known Lie-Baecklund symmetries and recursion operators of corresponding unperturbed equation. The perturbed Burgers equation and the perturbed Korteweg-de Vries (KdV) equation are used as examples.

  15. Parent-directed approaches to enrich the early language environments of children living in poverty.

    Leffel, Kristin; Suskind, Dana

    2013-11-01

    Children's early language environments are critical for their cognitive development, school readiness, and ultimate educational attainment. Significant disparities exist in these environments, with profound and lasting impacts upon children's ultimate outcomes. Children from backgrounds of low socioeconomic status experience diminished language inputs and enter school at a disadvantage, with disparities persisting throughout their educational careers. Parents are positioned as powerful agents of change in their children's lives, however, and evidence indicates that parent-directed intervention is effective in improving child outcomes. This article explores the efficacy of parent-directed interventions and their potential applicability to the wider educational achievement gap seen in typically developing populations of low socioeconomic status and then describes efforts to develop such interventions with the Thirty Million Words Project and Project ASPIRE (Achieving Superior Parental Involvement for Rehabilitative Excellence) curricula. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. A novel direct carbon fuel cell by approach of tubular solid oxide fuel cells

    Liu, Renzhu; Zhao, Chunhua; Li, Junliang; Zeng, Fanrong; Wang, Shaorong; Wen, Tinglian; Wen, Zhaoyin [CAS Key Laboratory of Materials for Energy Conversion, Shanghai Inorganic Energy Materials and Power Source Engineering Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS), 1295 Dingxi Road, Shanghai 200050 (China)

    2010-01-15

    A direct carbon fuel cell based on a conventional anode-supported tubular solid oxide fuel cell, which consisted of a NiO-YSZ anode support tube, a NiO-ScSZ anode functional layer, a ScSZ electrolyte film, and a LSM-ScSZ cathode, has been successfully achieved. It used the carbon black as fuel and oxygen as the oxidant, and a preliminary examination of the DCFC has been carried out. The cell generated an acceptable performance with the maximum power densities of 104, 75, and 47 mW cm{sup -2} at 850, 800, and 750 C, respectively. These results demonstrate the feasibility for carbon directly converting to electricity in tubular solid oxide fuel cells. (author)

  17. Direct approach to operator conformal constructions: from fermions to primary fields

    Halpern, M.B.

    1989-01-01

    I discuss the direct solution of Sugawara and coset constructions, including a path to construction of the primary fields. The basic tools are (1) a construction of affine-conformal highest-weight states, pretensors and tensors form quantum-irreducible representations of the currents of affine g, and (2) construction of primary fields by factorization and boosting of the pretensors. Large classes of pretensors are easily obtained in fermionic constructions, and guesswork is minimized with factorization of bosonized fermionic pretensors: The simplest case constructs conformal-weights h g =mN(n--N)/2n of SU m (n) and h K =mN(n--N)/n of SU m (n)direct-product SU m (n)/SU 2m (n) and extension to simply-laced g is clear. More general cases are left for future study. copyright Academic Prss, Inc. 1989

  18. Newspaper advertising versus direct mail marketing in a family practice: a hands-on approach.

    Godreau, C J

    1995-01-01

    This study compares newspaper advertising and direct mail marketing to attract private patients. Newsletter advertising was distributed to 92,251 homes throughout 1991 at a cost of $20,827.13. Newspaper advertising was conducted from August 28 to October 9, 1991 at a cost of $2,261.94. The newsletter attracted 101 new patients at a cost of $206.21 per patient and a mean response rate of 0.11%. No new patients were attracted through newspaper advertising.

  19. Direction of Coupling from Phases of Interacting Oscillators: A Permutation Information Approach

    Bahraminasab, A.; Ghasemi, F.; Stefanovska, A.; McClintock, P. V. E.; Kantz, H.

    2008-02-01

    We introduce a directionality index for a time series based on a comparison of neighboring values. It can distinguish unidirectional from bidirectional coupling, as well as reveal and quantify asymmetry in bidirectional coupling. It is tested on a numerical model of coupled van der Pol oscillators, and applied to cardiorespiratory data from healthy subjects. There is no need for preprocessing and fine-tuning the parameters, which makes the method very simple, computationally fast and robust.

  20. The EU Nitrates Directive: A European Approach to Combat Water Pollution from Agriculture

    Gert J. Monteny

    2001-01-01

    Full Text Available From 1991 onward, the European Union (EU member states have had to comply with the Nitrates Directive. The aim of this directive is to sustainably protect ground and surface waters from pollution with nitrogen (nitrate originating from agriculture. Agriculture is, on an EU level, the largest single source of nitrate (runoff, leaching pollution, although households and industries also contribute to some extent. An important element in the directive is the reporting every 4 years on the monitoring of ground- and surface-water quality. Furthermore, all 15 member states are compelled to designate so-called Nitrate Vulnerable Zones (NVZs. These are regions where the nitrate concentrations in the groundwater amount to 50 mg/l or more. In addition to Codes of Good Agricultural Practice, valid on a countrywide basis and often consisting of voluntary-based measures, specific Action Programmes with mandatory measures have to be developed for the NVZs. The first reporting period ended in 1995. This paper describes the progress in member states’ compliance with the Nitrates Directive during the second period (1996–1999, with a focus on the agricultural practices and action pro- grammes. An evaluation of the member states’ reports shows that good progress is being made on the farmers’ awareness of the need to comply with EU regulations on the protection of the aquatic environment. Action programmes are valuable tools to enforce measures that lead to a reduction of the water pollution by agricultural activities. Regional projects show that significant improvements can be achieved (e.g., reduced fertiliser inputs while maintaining crop yields and thus maintaining the economic potential of agriculture.

  1. Reconciling ocean mass content change based on direct and inverse approaches by utilizing data from GRACE, altimetry and Swarm

    Rietbroek, R.; Uebbing, B.; Lück, C.; Kusche, J.

    2017-12-01

    Ocean mass content (OMC) change due to the melting of the ice-sheets in Greenland and Antarctica, melting of glaciers and changes in terrestrial hydrology is a major contributor to present-day sea level rise. Since 2002, the GRACE satellite mission serves as a valuable tool for directly measuring the variations in OMC. As GRACE has almost reached the end of its lifetime, efforts are being made to utilize the Swarm mission for the recovery of low degree time-variable gravity fields to bridge a possible gap until the GRACE-FO mission and to fill up periods where GRACE data was not existent. To this end we compute Swarm monthly normal equations and spherical harmonics that are found competitive to other solutions. In addition to directly measuring the OMC, combination of GRACE gravity data with altimetry data in a global inversion approach allows to separate the total sea level change into individual mass-driven and steric contributions. However, published estimates of OMC from the direct and inverse methods differ not only depending on the time window, but also are influenced by numerous post-processing choices. Here, we will look into sources of such differences between direct and inverse approaches and evaluate the capabilities of Swarm to derive OMC. Deriving time series of OMC requires several processing steps; choosing a GRACE (and altimetry) product, data coverage, masks and filters to be applied in either spatial or spectral domain, corrections related to spatial leakage, GIA and geocenter motion. In this study, we compare and quantify the effects of the different processing choices of the direct and inverse methods. Our preliminary results point to the GIA correction as the major source of difference between the two approaches.

  2. A multi-technique approach for characterizing the geomorphological evolution of a Villerville-Cricqueboeuf coastal landslide (Normandy, France).

    Lissak Borges, Candide; Maquaire, Olivier; Malet, Jean-Philippe; Gomez, Christopher; Lavigne, Franck

    2010-05-01

    The Villerville and Cricqueboeuf coastal landslides (Calvados, Normandy, North-West France) have occurred in marly, sandy and chalky formations. The slope instability probably started during the last Quaternary period and is still active over the recent historic period. Since 1982, the slope is affected by a permanent activity (following the Varnes classification) with an annual average displacement of 5-10 cm.y-1 depending on the season. Three major events occurred in 1988, 1995 and 2001 and are controlled by the hydro-climatic conditions. These events induced pluri-decimetres to pluri-meters displacements (e.g. 5m horizontal displacements have been observed in 2001 at Cricqueboeuf) and generated economical and physical damage to buildings and roads. The landslide morphology is characterized by multi-metres scarps, reverse slopes caused by the tilting of landslide blocks and evolving cracks. The objective of this paper is to present the methodology used to characterize the recent historical (since 1808) geomorphological evolution of the landslides, and to discuss the spatio-temporal pattern of observed displacements. A multi-technique research approach has been applied and consisted in historical research, geomorphological mapping, geodetic monitoring and engineering geotechnical investigation. Information gained from different documents and techniques has been combined to propose a conceptual model of landslide evolution: - a retrospective study on landslide events inventoried in the historic period (archive investigation, newspapers); - a multi-temporal (1955-2006) analysis of aerial photographs (image processing, traditional stereoscopic techniques and image orthorectification), ancient maps and cadastres; - the creation of a detailed geomorphological map in 2009; - an analysis of recent displacements monitored since 1985 with traditional geodetic techniques (tacheometry, dGPS, micro-levelling) - geophysical investigation by ground-penetrating radar along the

  3. New Modeling Approaches to Study DNA Damage by the Direct and Indirect Effects of Ionizing Radiation

    Plante, Ianik; Cucinotta, Francis A.

    2012-01-01

    DNA is damaged both by the direct and indirect effects of radiation. In the direct effect, the DNA itself is ionized, whereas the indirect effect involves the radiolysis of the water molecules surrounding the DNA and the subsequent reaction of the DNA with radical products. While this problem has been studied for many years, many unknowns still exist. To study this problem, we have developed the computer code RITRACKS [1], which simulates the radiation track structure for heavy ions and electrons, calculating all energy deposition events and the coordinates of all species produced by the water radiolysis. In this work, we plan to simulate DNA damage by using the crystal structure of a nucleosome and calculations performed by RITRACKS. The energy deposition events are used to calculate the dose deposited in nanovolumes [2] and therefore can be used to simulate the direct effect of the radiation. Using the positions of the radiolytic species with a radiation chemistry code [3] it will be possible to simulate DNA damage by indirect effect. The simulation results can be compared with results from previous calculations such as the frequencies of simple and complex strand breaks [4] and with newer experimental data using surrogate markers of DNA double ]strand breaks such as . ]H2AX foci [5].

  4. Highly efficient direct Z-scheme WO3/CdS-diethylenetriamine photocatalyst and its enhanced photocatalytic H2 evolution under visible light irradiation

    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.

  5. Direct evidence for a systematic evolution of optical band gap and local disorder in Ag, in doped Sb{sub 2}Te phase change material

    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)

  6. 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".

    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.

  7. 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”

    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.

  8. Molecular Phytopathology: Current Approaches and Main Directions in Diagnostics of Woody Plant Diseases

    O. Yu. Baranov

    2014-08-01

    Full Text Available In the article the authors describe the prospects for diagnosis of woody plants diseases based on the use of modern methods of molecular plant pathology. The metagenomic approach based on the analysis of complex pathogens, including non-pathogenic microflora is described. The use the multicopy universal loci characterized by a number of advantages in determining taxonomic affiliation of infectious agents during phytopathological molecular analysis is proposed.

  9. Direct torque control method applied to the WECS based on the PMSG and controlled with backstepping approach

    Errami, Youssef; Obbadi, Abdellatif; Sahnoun, Smail; Ouassaid, Mohammed; Maaroufi, Mohamed

    2018-05-01

    This paper proposes a Direct Torque Control (DTC) method for Wind Power System (WPS) based Permanent Magnet Synchronous Generator (PMSG) and Backstepping approach. In this work, generator side and grid-side converter with filter are used as the interface between the wind turbine and grid. Backstepping approach demonstrates great performance in complicated nonlinear systems control such as WPS. So, the control method combines the DTC to achieve Maximum Power Point Tracking (MPPT) and Backstepping approach to sustain the DC-bus voltage and to regulate the grid-side power factor. In addition, control strategy is developed in the sense of Lyapunov stability theorem for the WPS. Simulation results using MATLAB/Simulink validate the effectiveness of the proposed controllers.

  10. Systems analysis approach to the design of efficient water pricing policies under the EU water framework directive

    Riegels, Niels; Pulido-Velazquez, Manuel; Doulgeris, Charalampos

    2013-01-01

    management objectives. However, the design and implementation of economic instruments for water management, including water pricing, has emerged as a challenging aspect of WFD implementation. This study demonstrates the use of a systems analysis approach to designing and comparing two economic approaches......Economic theory suggests that water pricing can contribute to efficient management of water scarcity. The European Union (EU) Water Framework Directive (WFD) is a major legislative effort to introduce the use of economic instruments to encourage efficient water use and achieve environmental...... to efficient management of groundwater and surface water given EU WFD ecological flow requirements. Under the first approach, all wholesale water users in a river basin face the same volumetric price for water. This water price does not vary in space or in time, and surface water and groundwater are priced...

  11. Direct calculation of resonance energies and widths using an R-matrix approach

    Schneider, B.I.

    1981-01-01

    A modified R-matrix technique is presented which determines the eigenvalues and widths of resonant states by the direct diagonalization of a complex, non-Hermitian matrix. The method utilizes only real basis sets and requires a minimum of complex arithmetic. The method is applied to two problems, a set of coupled square wells and the Pi/sub g/ resonance of N 2 in the static-exchange approximation. The results of the calculation are in good agreement with other methods and converge very quickly with basis-set size

  12. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

    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.

  13. Supercapacitor electrodes by direct growth of multi-walled carbon nanotubes on Al: a study of performance versus layer growth evolution

    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

  14. A Direct-Learning Approach to Acquiring a Bimanual Tapping Skill.

    Michaels, Claire F; Gomes, Thábata V B; Benda, Rodolfo N

    2017-01-01

    The theory of direct learning (D. M. Jacobs & C. F. Michaels, 2007 ) has proven useful in understanding improvement in perception and exploratory action. Here the authors assess its usefulness for understanding the learning of a motor skill, bimanual tapping at a difficult phase relation. Twenty participants attempted to learn to tap with 2 index fingers at 2 Hz with a phase lag of 90° (i.e., with a right-right period of 500 ms and a right-left period of 125 ms). There were 30 trials, each with 50 tapping cycles. Computer-screen feedback informed of errors in both period and phase for each pair of taps. Participants differed dramatically in their success. Learning was assessed by identifying the succession of attractors capturing tapping over the experiment. A few participants' attractors migrated from antiphase to 90° with an appropriate period; others became attracted to a fixed right-left interval, rather than phase, with or without attraction to period. Changes in attractor loci were explained with mixed success by direct learning, inviting elaboration of the theory. The transition to interval attractors was understood as a change in intention, and was remarkable for its indifference to typical bimanual interactions.

  15. Identification of important nodes in directed biological networks: a network motif approach.

    Pei Wang

    Full Text Available Identification of important nodes in complex networks has attracted an increasing attention over the last decade. Various measures have been proposed to characterize the importance of nodes in complex networks, such as the degree, betweenness and PageRank. Different measures consider different aspects of complex networks. Although there are numerous results reported on undirected complex networks, few results have been reported on directed biological networks. Based on network motifs and principal component analysis (PCA, this paper aims at introducing a new measure to characterize node importance in directed biological networks. Investigations on five real-world biological networks indicate that the proposed method can robustly identify actually important nodes in different networks, such as finding command interneurons, global regulators and non-hub but evolutionary conserved actually important nodes in biological networks. Receiver Operating Characteristic (ROC curves for the five networks indicate remarkable prediction accuracy of the proposed measure. The proposed index provides an alternative complex network metric. Potential implications of the related investigations include identifying network control and regulation targets, biological networks modeling and analysis, as well as networked medicine.

  16. Size-Induced Switching of Nanowire Growth Direction: a New Approach Toward Kinked Nanostructures

    Shen, Youde

    2016-04-26

    Exploring self-assembled nanostructures with controllable architectures has been a central theme in nanoscience and nanotechnology because of the tantalizing perspective of directly integrating such bottom-up nanostructures into functional devices. Here, the growth of kinked single-crystal In2O3 nanostructures consisting of a nanocone base and a nanowire tip with an epitaxial and defect-free transition is demonstrated for the first time. By tailoring the growth conditions, a reliable switching of the growth direction from [111] to [110] or [112] is observed when the Au catalyst nanoparticles at the apexes of the nanocones shrink below ≈100 nm. The natural formation of kinked nanoarchitectures at constant growth pressures is related to the size-dependent free energy that changes for different orientations of the nanowires. The results suggest that the mechanism of forming such kinked nanocone-nanowire nanostructures in well-controlled growth environment may be universal for a wide range of functional materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Size-Induced Switching of Nanowire Growth Direction: a New Approach Toward Kinked Nanostructures

    Shen, Youde; Lebedev, Oleg I.; Turner, Stuart; Van Tendeloo, Gustaaf; Song, Xiaohui; Yu, Xuechao; Wang, Qijie; Chen, Hongyu; Dayeh, Shadi A.; Wu, Tao

    2016-01-01

    Exploring self-assembled nanostructures with controllable architectures has been a central theme in nanoscience and nanotechnology because of the tantalizing perspective of directly integrating such bottom-up nanostructures into functional devices. Here, the growth of kinked single-crystal In2O3 nanostructures consisting of a nanocone base and a nanowire tip with an epitaxial and defect-free transition is demonstrated for the first time. By tailoring the growth conditions, a reliable switching of the growth direction from [111] to [110] or [112] is observed when the Au catalyst nanoparticles at the apexes of the nanocones shrink below ≈100 nm. The natural formation of kinked nanoarchitectures at constant growth pressures is related to the size-dependent free energy that changes for different orientations of the nanowires. The results suggest that the mechanism of forming such kinked nanocone-nanowire nanostructures in well-controlled growth environment may be universal for a wide range of functional materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Remediation approaches for polycyclic aromatic hydrocarbons (PAHs) contaminated soils: Technological constraints, emerging trends and future directions.

    Kuppusamy, Saranya; Thavamani, Palanisami; Venkateswarlu, Kadiyala; Lee, Yong Bok; Naidu, Ravi; Megharaj, Mallavarapu

    2017-02-01

    For more than a decade, the primary focus of environmental experts has been to adopt risk-based management approaches to cleanup PAH polluted sites that pose potentially destructive ecological consequences. This focus had led to the development of several physical, chemical, thermal and biological technologies that are widely implementable. Established remedial options available for treating PAH contaminated soils are incineration, thermal conduction, solvent extraction/soil washing, chemical oxidation, bioaugmentation, biostimulation, phytoremediation, composting/biopiles and bioreactors. Integrating physico-chemical and biological technologies is also widely practiced for better cleanup of PAH contaminated soils. Electrokinetic remediation, vermiremediation and biocatalyst assisted remediation are still at the development stage. Though several treatment methods to remediate PAH polluted soils currently exist, a comprehensive overview of all the available remediation technologies to date is necessary so that the right technology for field-level success is chosen. The objective of this review is to provide a critical overview in this respect, focusing only on the treatment options available for field soils and ignoring the spiked ones. The authors also propose the development of novel multifunctional green and sustainable systems like mixed cell culture system, biosurfactant flushing, transgenic approaches and nanoremediation in order to overcome the existing soil- contaminant- and microbial-associated technological limitations in tackling high molecular weight PAHs. The ultimate objective is to ensure the successful remediation of long-term PAH contaminated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. A direct comparison of remote sensing approaches for high-throughput phenotyping in plant breeding

    Maria Tattaris

    2016-08-01

    Full Text Available Remote sensing (RS of plant canopies permits non-intrusive, high-throughput monitoring of plant physiological characteristics. This study compared three RS approaches using a low flying UAV (unmanned aerial vehicle, with that of proximal sensing, and satellite-based imagery. Two physiological traits were considered, canopy temperature (CT and a vegetation index (NDVI, to determine the most viable approaches for large scale crop genetic improvement. The UAV-based platform achieves plot-level resolution while measuring several hundred plots in one mission via high-resolution thermal and multispectral imagery measured at altitudes of 30-100 m. The satellite measures multispectral imagery from an altitude of 770 km. Information was compared with proximal measurements using IR thermometers and an NDVI sensor at a distance of 0.5-1m above plots. For robust comparisons, CT and NDVI were assessed on panels of elite cultivars under irrigated and drought conditions, in different thermal regimes, and on un-adapted genetic resources under water deficit. Correlations between airborne data and yield/biomass at maturity were generally higher than equivalent proximal correlations. NDVI was derived from high-resolution satellite imagery for only larger sized plots (8.5 x 2.4 m due to restricted pixel density. Results support use of UAV-based RS techniques for high-throughput phenotyping for both precision and efficiency.

  20. Evidence-based evolution of an integrated nutrition-focused agriculture approach to address the underlying determinants of stunting.

    Haselow, Nancy J; Stormer, Ame; Pries, Alissa

    2016-05-01

    Despite progress in reducing hunger and malnutrition since the 1990s, many still suffer from undernutrition and food insecurity, particularly women and young children, resulting in preterm birth, low birthweight and stunting, among other conditions. Helen Keller International (HKI) has addressed malnutrition and household food insecurity through implementation of an Enhanced Homestead Food Production (EHFP) programme that increases year-round availability and intake of diverse micronutrient-rich foods and promotes optimal nutrition and hygiene practices among poor households. This paper reviews the evolution and impact of HKI's EHFP programme and identifies core components of the model that address the underlying determinants of stunting. To date, evaluations of EHFP have shown impact on food production, consumption by women and children and household food security. Sale of surplus produce has increased household income, and the use of a transformative gender approach has empowered women. EHFP has also realized nutrition improvements in many project sites. Results from a randomized control trial (RCT) in Baitadi district, Nepal showed a significant improvement in a range of practices known to impact child growth, although no impact on stunting. Additional non-RCT evaluations in Kailali district of Nepal, demonstrated a 10.5% reduction in stunting and in the Chittagong Hill Tracts in Bangladesh, revealed an 18% decrease in stunting. Based on evidence, the EHFP has evolved into an integrated package that includes agriculture, nutrition, water/hygiene/sanitation, linkages to health care, women's empowerment, income generation and advocacy. Closing the stunting gap requires long-term exposure to targeted multi-sectoral solutions and rigorous evaluation to optimize impact. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

  1. Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule.

    Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Granville, Michelle; Jacobson, Robert E

    2018-03-14

    Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning.

  2. Study of lattice strain evolution during biaxial deformation of stainless steel using a finite element and fast Fourier transform based multi-scale approach

    Upadhyay, M.V.; Van Petegem, S.; Panzner, T.; Lebensohn, R.A.; Van Swygenhoven, H.

    2016-01-01

    A multi-scale elastic-plastic finite element and fast Fourier transform based approach is proposed to study lattice strain evolution during uniaxial and biaxial loading of stainless steel cruciform shaped samples. At the macroscale, finite element simulations capture the complex coupling between applied forces in the arms and gauge stresses induced by the cruciform geometry. The predicted gauge stresses are used as macroscopic boundary conditions to drive a mesoscale elasto-viscoplastic fast Fourier transform model, from which lattice strains are calculated for particular grain families. The calculated lattice strain evolution matches well with experimental values from in-situ neutron diffraction measurements and demonstrates that the spread in lattice strain evolution between different grain families decreases with increasing biaxial stress ratio. During equibiaxial loading, the model reveals that the lattice strain evolution in all grain families, and not just the 311 grain family, is representative of the polycrystalline response. A detailed quantitative analysis of the 200 and 220 grain family reveals that the contribution of elastic and plastic anisotropy to the lattice strain evolution significantly depends on the applied stress ratio.

  3. A comparative study of approaches to direct methanol fuel cells modelling

    Oliveira, V.B.; Falcao, D.S.; Pinto, A.M.F.R. [Centro de Estudos de Fenomenos de Transporte, Departamento de Eng. Quimica, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Rangel, C.M. [Instituto Nacional de Engenharia, Tecnologia e Inovacao, Paco do Lumiar, 22,1649-038 (Portugal)

    2007-03-15

    Fuel cell modelling has received much attention over the past decade in an attempt to better understand the phenomena occurring within the cell. Mathematical models and simulation are needed as tools for design optimization of fuel cells, stacks and fuel cell power systems. Analytical, semi-empirical and mechanistic models for direct methanol fuel cells (DMFC) are reviewed. Effective models were until now developed describing the fundamental electrochemical and transport phenomena taking place in the cell. More research is required to develop models that can account for the two-phase flows occurring in the anode and cathode of the DMFC. The merits and demerits of the models are presented. Selected models of different categories are implemented and discussed. Finally, one of the selected simplified models is proposed as a computer-aided tool for real-time system level DMFC calculations. (author)

  4. Synthesis-based approach toward direct sandwich immunoassay for ciguatoxin CTX3C.

    Oguri, Hiroki; Hirama, Masahiro; Tsumuraya, Takeshi; Fujii, Ikuo; Maruyama, Megumi; Uehara, Hisatoshi; Nagumo, Yoko

    2003-06-25

    Ciguatoxins are the major causative toxins of ciguatera seafood poisoning. Limited availability of ciguatoxins has hampered the development of a reliable and specific immunoassay for detecting these toxins in contaminated fish. Monoclonal antibodies (mAbs) specific against both ends of ciguatoxin CTX3C were prepared by immunization of mice with protein conjugates of rationally designed synthetic haptens, 3 and 4, in place of the natural toxin. Haptenic groups that possess a surface area larger than 400 A(2) were required to produce mAbs that can bind strongly to CTX3C itself. A direct sandwich enzyme-linked immunosorbent assay (ELISA) using these mAbs was established to detect CTX3C at the ppb level with no cross-reactivity against other related marine toxins, including brevetoxin A, brevetoxin B, okadaic acid, or maitotoxin.

  5. A finite volume alternate direction implicit approach to modeling selective laser melting

    Hattel, Jesper Henri; Mohanty, Sankhya

    2013-01-01

    Over the last decade, several studies have attempted to develop thermal models for analyzing the selective laser melting process with a vision to predict thermal stresses, microstructures and resulting mechanical properties of manufactured products. While a holistic model addressing all involved...... to accurately simulate the process, are constrained by either the size or scale of the model domain. A second challenging aspect involves the inclusion of non-linear material behavior into the 3D implicit FE models. An alternating direction implicit (ADI) method based on a finite volume (FV) formulation...... is proposed for modeling single-layer and few-layers selective laser melting processes. The ADI technique is implemented and applied for two cases involving constant material properties and non-linear material behavior. The ADI FV method consume less time while having comparable accuracy with respect to 3D...

  6. The Nordic welfare model providing energy transition? A political geography approach to the EU RES directive

    Westholm, Erik; Beland Lindahl, Karin

    2012-01-01

    The EU Renewable Energy Strategy (RES) Directive requires that each member state obtain 20% of its energy supply from renewable sources by 2020. If fully implemented, this implies major changes in institutions, infrastructure, land use, and natural resource flows. This study applies a political geography perspective to explore the transition to renewable energy use in the heating and cooling segment of the Swedish energy system, 1980–2010. The Nordic welfare model, which developed mainly after the Second World War, required relatively uniform, standardized local and regional authorities functioning as implementation agents for national politics. Since 1980, the welfare orientation has gradually been complemented by competition politics promoting technological change, innovation, and entrepreneurship. This combination of welfare state organization and competition politics provided the dynamics necessary for energy transition, which occurred in a semi-public sphere of actors at various geographical scales. However, our analysis, suggest that this was partly an unintended policy outcome, since it was based on a welfare model with no significant energy aims. Our case study suggests that state organization plays a significant role, and that the EU RES Directive implementation will be uneven across Europe, reflecting various welfare models with different institutional pre-requisites for energy transition. - Highlights: ► We explore the energy transition in the heating/cooling sector in Sweden 1980–2000. ► The role of the state is studied from a political geography perspective. ► The changing welfare model offered the necessary institutional framework. ► Institutional arrangements stand out as central to explain the relative success. ► The use of renewables in EU member states will continue to vary significantly.

  7. Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

    Kant, Rajeev J; Coulombe, Kareen L K

    2018-03-15

    The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue

  8. Rotating shaft model updating from modal data by a direct energy approach : a feasibility study

    Audebert, S.

    1996-01-01

    Investigations to improve the rotating machinery monitoring tend more and more to use numerical models. The aim is to obtain multi-fluid bearing rotor models which are able to correctly represent their dynamic behaviour, either modal or forced response type. The possibility of extending the direct energy method, initially developed for undamped structures, to rotating machinery is studied. It is based on the minimization of the kinetic and strain energy gap between experimental and analytic modal data. The preliminary determination of a multi-linear bearing rotor system Eigen modes shows the problem complexity in comparison with undamped non rotating structures: taking into account gyroscopic effects and bearing damping, as factors of rotor velocities, leads to complex component Eigen modes; moreover, non symmetric matrices, related to stiffness and damping bearing contributions, induce distinct left and right-hand side Eigen modes (left hand side Eigenmodes corresponds to the adjoint structure). Theoretically, the extension of the energy method is studied, considering first the intermediate case of an undamped non gyroscopic structure, second the general case of a rotating shaft: dta used for updating procedure are Eigen frequencies and left- and right- hand side mode shapes. Since left hand side mode shapes cannot be directly measured, they are replaced by analytic ones. The method is tested on a two-bearing rotor system, with a mass added; simulated data are used, relative to a non compatible structure, i.e. which is not a part of the set of modified analytic possible structures. Parameters to be corrected are the mass density, the Young's modulus, and the stiffness and damping linearized characteristics of bearings. If parameters are influent in regard with modes to be updates, the updating method permits a significant improvement of the gap between analytic and experimental modes, even for modes not involves in the procedure. Modal damping appears to be more

  9. Evaluating fossil calibrations for dating phylogenies in light of rates of molecular evolution: a comparison of three approaches.

    Lukoschek, Vimoksalehi; Scott Keogh, J; Avise, John C

    2012-01-01

    Evolutionary and biogeographic studies increasingly rely on calibrated molecular clocks to date key events. Although there has been significant recent progress in development of the techniques used for molecular dating, many issues remain. In particular, controversies abound over the appropriate use and placement of fossils for calibrating molecular clocks. Several methods have been proposed for evaluating candidate fossils; however, few studies have compared the results obtained by different approaches. Moreover, no previous study has incorporated the effects of nucleotide saturation from different data types in the evaluation of candidate fossils. In order to address these issues, we compared three approaches for evaluating fossil calibrations: the single-fossil cross-validation method of Near, Meylan, and Shaffer (2005. Assessing concordance of fossil calibration points in molecular clock studies: an example using turtles. Am. Nat. 165:137-146), the empirical fossil coverage method of Marshall (2008. A simple method for bracketing absolute divergence times on molecular phylogenies using multiple fossil calibration points. Am. Nat. 171:726-742), and the Bayesian multicalibration method of Sanders and Lee (2007. Evaluating molecular clock calibrations using Bayesian analyses with soft and hard bounds. Biol. Lett. 3:275-279) and explicitly incorporate the effects of data type (nuclear vs. mitochondrial DNA) for identifying the most reliable or congruent fossil calibrations. We used advanced (Caenophidian) snakes as a case study; however, our results are applicable to any taxonomic group with multiple candidate fossils, provided appropriate taxon sampling and sufficient molecular sequence data are available. We found that data type strongly influenced which fossil calibrations were identified as outliers, regardless of which method was used. Despite the use of complex partitioned models of sequence evolution and multiple calibrations throughout the tree, saturation

  10. Directed evolution of adaptive traits

    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...

  11. Bi-directional Reflectance of Icy Surface Analogs: A Dual Approach

    Quinones, Juan Manuel; Vides, Christina; Nelson, Robert M.; Boryta, Mark; Mannat, Ken s.

    2018-01-01

    Bi-directional reflectance measurements of analogs for planetary regolith have provided insight into the surface properties of planetary satellites and small bodies. Because Aluminum Oxide (Al2O3) and water ice share a similar hexagonal crystalline structure, the former has been used in laboratory experiments to simulate the regolith of both icy and dusty planetary bodies. By measuring various sizes of well sorted size fractions of Al2O3, the reflectance phase curve and porosity of a planetary regolith can be determined. We have designed an experiment to test the laboratory measurements produced by Nelson et al. (2000). Additionally, we made reflectance measurements for other alkali-halide compounds that could be used for applications beyond astronomy and planetary science.In order to provide an independent check on the Nelson et al. data, we designed an instrument with a different configuration. While both instruments take bidirectional reflectance measurements, our instrument, the Rigid Photometric Goniometer (RPG), is fixed at a phase angle of 5° and detects the scattered light with a photomultiplier tube (PMT). The PMT current is then measured with an electrometer. Following the example of Nelson et al., we measured the bidirectional reflectance of Al2O3 particulate size fractions between 0.1sizes from 20size that provided optimal, or maximum, reflectance for each compound. Our conclusions bring confirmation and clarity to photometric sciences.

  12. Theoretical approach to direct resonant inelastic X-ray scattering on magnets and superconductors

    Marra, Pasquale

    2015-10-26

    The capability to probe the dispersion of elementary spin, charge, orbital, and lattice excitations has positioned resonant inelastic X-ray scattering (RIXS) at the forefront of photon science. In this work, we will investigate how RIXS can contribute to a deeper understanding of the orbital properties and of the pairing mechanism in unconventional high-temperature superconductors. In particular, we show how direct RIXS spectra of magnetic excitations can reveal long-range orbital correlations in transition metal compounds, by discriminating different kind of orbital order in magnetic and antiferromagnetic systems. Moreover, we show how RIXS spectra of quasiparticle excitations in superconductors can measure the superconducting gap magnitude, and reveal the presence of nodal points and phase differences of the superconducting order parameter on the Fermi surface. This can reveal the properties of the underlying pairing mechanism in unconventional superconductors, in particular cuprates and iron pnictides, discriminating between different superconducting order parameter symmetries, such as s,d (singlet pairing) and p wave (triplet pairing).

  13. Non-Newtonian particulate flow simulation: A direct-forcing immersed boundary-lattice Boltzmann approach

    Amiri Delouei, A.; Nazari, M.; Kayhani, M. H.; Kang, S. K.; Succi, S.

    2016-04-01

    In the current study, a direct-forcing immersed boundary-non-Newtonian lattice Boltzmann method (IB-NLBM) is developed to investigate the sedimentation and interaction of particles in shear-thinning and shear-thickening fluids. In the proposed IB-NLBM, the non-linear mechanics of non-Newtonian particulate flows is detected by combination of the most desirable features of immersed boundary and lattice Boltzmann methods. The noticeable roles of non-Newtonian behavior on particle motion, settling velocity and generalized Reynolds number are investigated by simulating benchmark problem of one-particle sedimentation under the same generalized Archimedes number. The effects of extra force due to added accelerated mass are analyzed on the particle motion which have a significant impact on shear-thinning fluids. For the first time, the phenomena of interaction among the particles, such as Drafting, Kissing, and Tumbling in non-Newtonian fluids are investigated by simulation of two-particle sedimentation and twelve-particle sedimentation. The results show that increasing the shear-thickening behavior of fluid leads to a significant increase in the kissing time. Moreover, the transverse position of particles for shear-thinning fluids during the tumbling interval is different from Newtonian and the shear-thickening fluids. The present non-Newtonian particulate study can be applied in several industrial and scientific applications, like the non-Newtonian sedimentation behavior of particles in food industrial and biological fluids.

  14. A novel multi-stage direct contact membrane distillation module: Design, experimental and theoretical approaches

    Lee, Jung Gil

    2016-10-24

    An economic desalination system with a small scale and footprint for remote areas, which have a limited and inadequate water supply, insufficient water treatment and low infrastructure, is strongly demanded in the desalination markets. Here, a direct contact membrane distillation (DCMD) process has the simplest configuration and potentially the highest permeate flux among all of the possible MD processes. This process can also be easily instituted in a multi-stage manner for enhanced compactness, productivity, versatility and cost-effectiveness. In this study, an innovative, multi-stage, DCMD module under countercurrent-flow configuration is first designed and then investigate both theoretically and experimentally to identify its feasibility and operability for desalination application. Model predictions and measured data for mean permeate flux are compared and shown to be in good agreement. The effect of the number of module stages on the mean permeate flux, performance ratio and daily water production of the MDCMD system has been theoretically identified at inlet feed and permeate flow rates of 1.5 l/min and inlet feed and permeate temperatures of 70 °C and 25 °C, respectively. The daily water production of a three-stage DCMD module with a membrane area of 0.01 m2 at each stage is found to be 21.5 kg.

  15. A New Method to Directly Observe Tuberculosis Treatment: Skype Observed Therapy, a Patient-Centered Approach.

    Buchman, Tavora; Cabello, Celina

    Tuberculosis (TB) treatment completion is in part determined by patient's adherence to long-term drug regimens. To best ensure compliance, directly observed therapy (DOT) is considered the standard of practice. Nassau County Department of Health TB Control is responsible for providing DOT to patients with TB. Tuberculosis Control sought to use and evaluate Skype Observed Therapy (SOT) as an alternative to DOT for eligible patients. The evaluation included analysis of patient's acceptance and adherence to drug regimen using SOT. Tuberculosis Control assessed staff efficiency and cost savings for this program. Percentages of SOT of patients and successful SOT visits, mileage, and travel time savings. Twenty percent of the caseload used SOT and 100% of patients who were eligible opted in. Average SOT success was 79%. Total mileage savings and time saved were $9,929.07 and 614 hours. Because SOT saves cost and time and is a suitable alternative to DOT for patients, it should be considered as part of new policies and practices in TB control programs.

  16. A novel multi-stage direct contact membrane distillation module: Design, experimental and theoretical approaches.

    Lee, Jung-Gil; Kim, Woo-Seung; Choi, June-Seok; Ghaffour, Noreddine; Kim, Young-Deuk

    2016-12-15

    An economic desalination system with a small scale and footprint for remote areas, which have a limited and inadequate water supply, insufficient water treatment and low infrastructure, is strongly demanded in the desalination markets. Here, a direct contact membrane distillation (DCMD) process has the simplest configuration and potentially the highest permeate flux among all of the possible MD processes. This process can also be easily instituted in a multi-stage manner for enhanced compactness, productivity, versatility and cost-effectiveness. In this study, an innovative, multi-stage, DCMD module under countercurrent-flow configuration is first designed and then investigate both theoretically and experimentally to identify its feasibility and operability for desalination application. Model predictions and measured data for mean permeate flux are compared and shown to be in good agreement. The effect of the number of module stages on the mean permeate flux, performance ratio and daily water production of the MDCMD system has been theoretically identified at inlet feed and permeate flow rates of 1.5 l/min and inlet feed and permeate temperatures of 70 °C and 25 °C, respectively. The daily water production of a three-stage DCMD module with a membrane area of 0.01 m 2  at each stage is found to be 21.5 kg. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Combinatorial approach toward high-throughput analysis of direct methanol fuel cells.

    Jiang, Rongzhong; Rong, Charles; Chu, Deryn

    2005-01-01

    A 40-member array of direct methanol fuel cells (with stationary fuel and convective air supplies) was generated by electrically connecting the fuel cells in series. High-throughput analysis of these fuel cells was realized by fast screening of voltages between the two terminals of a fuel cell at constant current discharge. A large number of voltage-current curves (200) were obtained by screening the voltages through multiple small-current steps. Gaussian distribution was used to statistically analyze the large number of experimental data. The standard deviation (sigma) of voltages of these fuel cells increased linearly with discharge current. The voltage-current curves at various fuel concentrations were simulated with an empirical equation of voltage versus current and a linear equation of sigma versus current. The simulated voltage-current curves fitted the experimental data well. With increasing methanol concentration from 0.5 to 4.0 M, the Tafel slope of the voltage-current curves (at sigma=0.0), changed from 28 to 91 mV.dec-1, the cell resistance from 2.91 to 0.18 Omega, and the power output from 3 to 18 mW.cm-2.

  18. Directive and incentive functions of affective action consequences: an ideomotor approach.

    Eder, Andreas B; Rothermund, Klaus; De Houwer, Jan; Hommel, Bernhard

    2015-07-01

    Five experiments examined whether affective consequences become associated with the responses producing them and whether anticipations of positive and negative action outcomes influence action control differently. In a learning phase, one response produced pleasant and another response unpleasant visual effects. In a subsequent test phase, the same actions were carried out in response to a neutral feature of affective stimuli. Results showed that responses were faster when the irrelevant valence of the response cue matched the valence of the response outcome, but only when the responses still produced outcomes. These results suggest that affective action consequences have a directive function in that they facilitate the selection of the associated response over other responses, even when the response outcome is unpleasant (Experiment 4A). Results of another experiment showed that affective action consequences can also have an incentive function in that responses with pleasant outcomes are generally facilitated relative to responses with unpleasant outcomes. However, this motivational effect was seen only in a free-choice test (Experiment 5). The results suggest that behavioral impulses induced by ideomotor processes are constrained by the motivational evaluation of the anticipated action outcome. A model that integrates motivational factors into ideomotor theory is presented.

  19. A hybrid bio-jetting approach for directly engineering living cells

    Kwok, Albert; Irvine, Scott; Arumuganathar, Sumathy; Jayasinghe, Suwan N; McEwan, Jean R

    2008-01-01

    This paper reports developments on a hybrid cell-engineering protocol coupling both bio-electrosprays and aerodynamically assisted bio-jets for process-handling living cells. The current work demonstrates the ability to couple these two cell-jetting protocols for handling a wide range of cells for deposition. The post-treated cells are assessed for their viability by way of flow cytometry, which illustrates a significant population of viable cells post-treatment in comparison to those controls. This work is the first example of coupling these two protocols for the process handling of living cells. The hybrid protocol demonstrates the achievement of stable cone jetting of a cellular suspension in the single-needle configuration which was previously unachieved with single-needle bio-electrosprays. Furthermore the living cells explored in these investigations expressed GFP, thus demonstrating the ability to couple gene therapy with this hybrid protocol. Hence, this approach could one day be explored for building biologically viable tissues incorporating a therapeutic payload for combating a range of cellular/tissue-based pathologies

  20. NORM - Radionuclide transfer studies - A modern approach according Directive 2013/59/EURATOM

    Prlic, Ivica; Hajdinjak, Mladen

    2014-01-01

    Regarding NORM, Directive applies in particular to human activities which involve the presence of natural radiation sources that lead to a significant increase in the exposure of workers or members of the public, in particular the processing of materials with naturally-occurring radionuclides (NORM) and the exposure of workers or members of the public to indoor radon, the external exposure from building materials and cases of lasting exposure resulting from the after-effects of an emergency or a past human activity. For areas with long-lasting residual contamination in which the Member State has decided to allow habitation and the resumption of social and economic activities, Member States shall ensure, in consultation with stakeholders, that arrangements are in place, as necessary, for the ongoing control of exposure with the aim of establishing living conditions that can be considered as normal. For building materials which are identified by the Member State as being of concern from a radiation protection point of view, Member State shall ensure that, before such materials are placed on the market the activity concentration index I is determined. The index relates to the gamma radiation dose derived throughout the radionuclide transfer studies, in excess of typical outdoor exposure, in a building constructed from a specified building material. The index applies to the building material, not to its constituents except when those constituents are building materials themselves and are separately assessed as such. The calculation of dose needs to take into account other factors such as density, thickness of the material as well as factors relating to the type of building and the intended use of the material (bulk or superficial). (authors)