WorldWideScience

Sample records for evolutionary mutant models

  1. Evolutionary genetics: the Drosophila model

    Indian Academy of Sciences (India)

    Unknown

    Evolutionary genetics straddles the two fundamental processes of life, ... of the genus Drosophila have been used extensively as model systems in experimental ... issue will prove interesting, informative and thought-provoking for both estab-.

  2. Fixation Probabilities of Evolutionary Graphs Based on the Positions of New Appearing Mutants

    Directory of Open Access Journals (Sweden)

    Pei-ai Zhang

    2014-01-01

    Full Text Available Evolutionary graph theory is a nice measure to implement evolutionary dynamics on spatial structures of populations. To calculate the fixation probability is usually regarded as a Markov chain process, which is affected by the number of the individuals, the fitness of the mutant, the game strategy, and the structure of the population. However the position of the new mutant is important to its fixation probability. Here the position of the new mutant is laid emphasis on. The method is put forward to calculate the fixation probability of an evolutionary graph (EG of single level. Then for a class of bilevel EGs, their fixation probabilities are calculated and some propositions are discussed. The conclusion is obtained showing that the bilevel EG is more stable than the corresponding one-rooted EG.

  3. Context dependent DNA evolutionary models

    DEFF Research Database (Denmark)

    Jensen, Jens Ledet

    This paper is about stochastic models for the evolution of DNA. For a set of aligned DNA sequences, connected in a phylogenetic tree, the models should be able to explain - in probabilistic terms - the differences seen in the sequences. From the estimates of the parameters in the model one can...... start to make biologically interpretations and conclusions concerning the evolutionary forces at work. In parallel with the increase in computing power, models have become more complex. Starting with Markov processes on a space with 4 states, and extended to Markov processes with 64 states, we are today...... studying models on spaces with 4n (or 64n) number of states with n well above one hundred, say. For such models it is no longer possible to calculate the transition probability analytically, and often Markov chain Monte Carlo is used in connection with likelihood analysis. This is also the approach taken...

  4. Evolutionary Models for Simple Biosystems

    Science.gov (United States)

    Bagnoli, Franco

    The concept of evolutionary development of structures constituted a real revolution in biology: it was possible to understand how the very complex structures of life can arise in an out-of-equilibrium system. The investigation of such systems has shown that indeed, systems under a flux of energy or matter can self-organize into complex patterns, think for instance to Rayleigh-Bernard convection, Liesegang rings, patterns formed by granular systems under shear. Following this line, one could characterize life as a state of matter, characterized by the slow, continuous process that we call evolution. In this paper we try to identify the organizational level of life, that spans several orders of magnitude from the elementary constituents to whole ecosystems. Although similar structures can be found in other contexts like ideas (memes) in neural systems and self-replicating elements (computer viruses, worms, etc.) in computer systems, we shall concentrate on biological evolutionary structure, and try to put into evidence the role and the emergence of network structure in such systems.

  5. Langley's CSI evolutionary model: Phase O

    Science.gov (United States)

    Belvin, W. Keith; Elliott, Kenny B.; Horta, Lucas G.; Bailey, Jim P.; Bruner, Anne M.; Sulla, Jeffrey L.; Won, John; Ugoletti, Roberto M.

    1991-01-01

    A testbed for the development of Controls Structures Interaction (CSI) technology to improve space science platform pointing is described. The evolutionary nature of the testbed will permit the study of global line-of-sight pointing in phases 0 and 1, whereas, multipayload pointing systems will be studied beginning with phase 2. The design, capabilities, and typical dynamic behavior of the phase 0 version of the CSI evolutionary model (CEM) is documented for investigator both internal and external to NASA. The model description includes line-of-sight pointing measurement, testbed structure, actuators, sensors, and real time computers, as well as finite element and state space models of major components.

  6. Evolutionary modelling of transitions to sustainable development

    International Nuclear Information System (INIS)

    Safarzynska, K.

    2010-01-01

    This thesis has examined how evolutionary economics can contribute to modelling the micromechanisms that underlie transitions towards sustainable development. In general, transitions are fundamental or structural system changes. They involve, or even require, escaping lock-in of dominant, environmentally unsustainable technologies, introducing major technical or social innovations, and changing prevailing social practices and structures. Due to the complexity of socioeconomic interactions, it is not always possible to identify, and thus target with appropriate policy instruments, causes of specific unsustainable patterns of behaviour. Formal modelling exercises can help improve our understanding of the interaction of various transition mechanisms which are otherwise difficult to grasp intuitively. They allow exploring effects of policy interventions in complex systems. However, existing models of transitions focus on social phenomena and seldom address economic problems. As opposed, mainstream (neoclassical) economic models of technological change do not account for social interactions, and changing heterogeneity of users and their perspectives - even though all of these can influence the direction of innovations and patterns of socio-technological development. Evolutionary economics offers an approach that goes beyond neoclassical economics - in the sense of employing more realistic assumptions regarding the behaviour and heterogeneity of consumers, firms and investors. It can complement current transition models by providing them with a better understanding of associated economic dynamics. In this thesis, formal models were proposed to illustrate the usefulness of a range of evolutionary-economic techniques for modelling transitions. Modelling exercises aimed to explain the core properties of socio-economic systems, such as lock-in, path-dependence, coevolution, group selection and recombinant innovation. The studies collected in this dissertation illustrate that

  7. Application of evolutionary games to modeling carcinogenesis.

    Science.gov (United States)

    Swierniak, Andrzej; Krzeslak, Michal

    2013-06-01

    We review a quite large volume of literature concerning mathematical modelling of processes related to carcinogenesis and the growth of cancer cell populations based on the theory of evolutionary games. This review, although partly idiosyncratic, covers such major areas of cancer-related phenomena as production of cytotoxins, avoidance of apoptosis, production of growth factors, motility and invasion, and intra- and extracellular signaling. We discuss the results of other authors and append to them some additional results of our own simulations dealing with the possible dynamics and/or spatial distribution of the processes discussed.

  8. An Evolutionary Model of Spatial Competition

    DEFF Research Database (Denmark)

    Knudsen, Thorbjørn; Winter, Sidney G.

      This paper sets forth an evolutionary model in which diverse businesses, with diverse offerings, compete in a stylized physical space.  When a business firm attempts to expand its activity, so as to profit further from the capabilities it has developed, it necessarily does so in a "new location...... as well in the new environment as they did in the old; the firm may respond with effort to locate appropriate environments or by modification of its routines.  Tradeoffs are presented between the complexity of a business model and its replication costs,  as well as issues involving response....... Randomly generated firm policies are tested first by a local market environment, and then, if success leads the firm to grow spatially, in a gradually expanding environment.  In the initial experiments reported here, we show that the model generates configurations that reflect features of the exogenous...

  9. An evolutionary algorithm for model selection

    Energy Technology Data Exchange (ETDEWEB)

    Bicker, Karl [CERN, Geneva (Switzerland); Chung, Suh-Urk; Friedrich, Jan; Grube, Boris; Haas, Florian; Ketzer, Bernhard; Neubert, Sebastian; Paul, Stephan; Ryabchikov, Dimitry [Technische Univ. Muenchen (Germany)

    2013-07-01

    When performing partial-wave analyses of multi-body final states, the choice of the fit model, i.e. the set of waves to be used in the fit, can significantly alter the results of the partial wave fit. Traditionally, the models were chosen based on physical arguments and by observing the changes in log-likelihood of the fits. To reduce possible bias in the model selection process, an evolutionary algorithm was developed based on a Bayesian goodness-of-fit criterion which takes into account the model complexity. Starting from systematically constructed pools of waves which contain significantly more waves than the typical fit model, the algorithm yields a model with an optimal log-likelihood and with a number of partial waves which is appropriate for the number of events in the data. Partial waves with small contributions to the total intensity are penalized and likely to be dropped during the selection process, as are models were excessive correlations between single waves occur. Due to the automated nature of the model selection, a much larger part of the model space can be explored than would be possible in a manual selection. In addition the method allows to assess the dependence of the fit result on the fit model which is an important contribution to the systematic uncertainty.

  10. Evolutionary modeling-based approach for model errors correction

    Directory of Open Access Journals (Sweden)

    S. Q. Wan

    2012-08-01

    Full Text Available The inverse problem of using the information of historical data to estimate model errors is one of the science frontier research topics. In this study, we investigate such a problem using the classic Lorenz (1963 equation as a prediction model and the Lorenz equation with a periodic evolutionary function as an accurate representation of reality to generate "observational data."

    On the basis of the intelligent features of evolutionary modeling (EM, including self-organization, self-adaptive and self-learning, the dynamic information contained in the historical data can be identified and extracted by computer automatically. Thereby, a new approach is proposed to estimate model errors based on EM in the present paper. Numerical tests demonstrate the ability of the new approach to correct model structural errors. In fact, it can actualize the combination of the statistics and dynamics to certain extent.

  11. Evolutionary sequence of models of planetary nebulae

    International Nuclear Information System (INIS)

    Vil'koviskij, Eh.Ya.; Kondrat'eva, L.N.; Tambovtseva, L.V.

    1983-01-01

    The evolutionary sequences of model planetary nebulae of different masses have been calculated. The computed emission line intensities are compared with the observed ones by means of the parameter ''reduced size of the nebula'', Rsub(n). It is shown that the evolution tracks of Schonberner for the central stars are consistent with the observed data. Part of ionized mass Mi in any nebulae does not not exceed 0.3 b and in the average Msu(i) 3 years at actual values of radius Rsub(i) <0.025 ps. Then the luminosity growth slows down to the maximum temperature which central star reaches and decreases with sharp decrease of the star luminosity. At that, the radius of ionized zone of greater mass nebulae can even decrease, inspite of the constant expansion of the nebula. As a result nebulae of great masses having undergone the evolution can be included in the number of observed compact objects (Rsub(n) < 0.1 ps)

  12. Modelling Evolutionary Algorithms with Stochastic Differential Equations.

    Science.gov (United States)

    Heredia, Jorge Pérez

    2017-11-20

    There has been renewed interest in modelling the behaviour of evolutionary algorithms (EAs) by more traditional mathematical objects, such as ordinary differential equations or Markov chains. The advantage is that the analysis becomes greatly facilitated due to the existence of well established methods. However, this typically comes at the cost of disregarding information about the process. Here, we introduce the use of stochastic differential equations (SDEs) for the study of EAs. SDEs can produce simple analytical results for the dynamics of stochastic processes, unlike Markov chains which can produce rigorous but unwieldy expressions about the dynamics. On the other hand, unlike ordinary differential equations (ODEs), they do not discard information about the stochasticity of the process. We show that these are especially suitable for the analysis of fixed budget scenarios and present analogues of the additive and multiplicative drift theorems from runtime analysis. In addition, we derive a new more general multiplicative drift theorem that also covers non-elitist EAs. This theorem simultaneously allows for positive and negative results, providing information on the algorithm's progress even when the problem cannot be optimised efficiently. Finally, we provide results for some well-known heuristics namely Random Walk (RW), Random Local Search (RLS), the (1+1) EA, the Metropolis Algorithm (MA), and the Strong Selection Weak Mutation (SSWM) algorithm.

  13. Evaluation of models generated via hybrid evolutionary algorithms ...

    African Journals Online (AJOL)

    2016-04-02

    Apr 2, 2016 ... Evaluation of models generated via hybrid evolutionary algorithms for the prediction of Microcystis ... evolutionary algorithms (HEA) proved to be highly applica- ble to the hypertrophic reservoirs of South Africa. .... discovered and optimised using a large-scale parallel computational device and relevant soft-.

  14. A Selective Bottleneck Shapes the Evolutionary Mutant Spectra of Enterovirus A71 during Viral Dissemination in Humans.

    Science.gov (United States)

    Huang, Sheng-Wen; Huang, Yi-Hui; Tsai, Huey-Pin; Kuo, Pin-Hwa; Wang, Shih-Min; Liu, Ching-Chuan; Wang, Jen-Ren

    2017-12-01

    RNA viruses accumulate mutations to rapidly adapt to environmental changes. Enterovirus A71 (EV-A71) causes various clinical manifestations with occasional severe neurological complications. However, the mechanism by which EV-A71 evolves within the human body is unclear. Utilizing deep sequencing and haplotype analyses of viruses from various tissues of an autopsy patient, we sought to define the evolutionary pathway by which enterovirus A71 evolves fitness for invading the central nervous system in humans. Broad mutant spectra with divergent mutations were observed at the initial infection sites in the respiratory and digestive systems. After viral invasion, we identified a haplotype switch and dominant haplotype, with glycine at VP1 residue 31 (VP1-31G) in viral particles disseminated into the integumentary and central nervous systems. In vitro viral growth and fitness analyses indicated that VP1-31G conferred growth and a fitness advantage in human neuronal cells, whereas VP1-31D conferred enhanced replication in human colorectal cells. A higher proportion of VP1-31G was also found among fatal cases, suggesting that it may facilitate central nervous system infection in humans. Our data provide the first glimpse of EV-A71 quasispecies from oral tissues to the central nervous system within humans, showing broad implications for the surveillance and pathogenesis of this reemerging viral pathogen. IMPORTANCE EV-A71 continues to be a worldwide burden to public health. Although EV-A71 is the major etiological agent of hand, foot, and mouth disease, it can also cause neurological pulmonary edema, encephalitis, and even death, especially in children. Understanding selection processes enabling dissemination and accurately estimating EV-A71 diversity during invasion in humans are critical for applications in viral pathogenesis and vaccine studies. Here, we define a selection bottleneck appearing in respiratory and digestive tissues. Glycine substitution at VP1 residue 31

  15. Natural variation of model mutant phenotypes in Ciona intestinalis.

    Directory of Open Access Journals (Sweden)

    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  16. Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

    Science.gov (United States)

    Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

    2008-01-01

    Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

  17. Dynamic Ising model: reconstruction of evolutionary trees

    International Nuclear Information System (INIS)

    De Oliveira, P M C

    2013-01-01

    An evolutionary tree is a cascade of bifurcations starting from a single common root, generating a growing set of daughter species as time goes by. ‘Species’ here is a general denomination for biological species, spoken languages or any other entity which evolves through heredity. From the N currently alive species within a clade, distances are measured through pairwise comparisons made by geneticists, linguists, etc. The larger is such a distance that, for a pair of species, the older is their last common ancestor. The aim is to reconstruct the previously unknown bifurcations, i.e. the whole clade, from knowledge of the N(N − 1)/2 quoted distances, which are taken for granted. A mechanical method is presented and its applicability is discussed. (paper)

  18. Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

    Science.gov (United States)

    Uhl, Elizabeth W; Warner, Natalie J

    Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

  19. Individual-based modeling of ecological and evolutionary processes

    NARCIS (Netherlands)

    DeAngelis, D.L.; Mooij, W.M.

    2005-01-01

    Individual-based models (IBMs) allow the explicit inclusion of individual variation in greater detail than do classical differential and difference equation models. Inclusion of such variation is important for continued progress in ecological and evolutionary theory. We provide a conceptual basis

  20. Hidden long evolutionary memory in a model biochemical network

    Science.gov (United States)

    Ali, Md. Zulfikar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-04-01

    We introduce a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. Starting with a functional core module, random evolutionary drift increases network complexity even in the absence of specific selective pressures. Surprisingly, we uncover a hidden order in sequence space that gives rise to long-term evolutionary memory, implying strong constraints on network evolution due to the topology of accessible sequence space.

  1. Antisense downregulation of mutant huntingtin in a cell model

    DEFF Research Database (Denmark)

    Hasholt, L.; Abell, K.; Norremolle, A.

    2003-01-01

    or by addition to the culture medium. Results Expression of the fusion protein containing the mutant huntingtin fragment resulted in diffuse green fluorescence in the cytoplasm and formation of aggregates in some of the NT2 cells and NT2-N neurons. We obtained antisense sequence-specific inhibition of expression...... of the fusion protein and/or suppression of the aggregate formation in both cell types. In the NT2 cells the antisense effect was dependent on the way of administration of the oligo. Conclusions The PS-antisense oligo is effective in downregulation of mutant huntingtin, and the reduction of aggregate formation...... is a sensitive biological marker. The findings suggest that antisense knockdown of huntingtin could be a useful strategy for treatment of HD, and could also be suitable for studies of the normal and pathological function of huntingtin in different cellular model systems....

  2. Modeling the dual pacemaker system of the tau mutant hamster.

    Science.gov (United States)

    Oda, G A; Menaker, M; Friesen, W O

    2000-06-01

    Circadian pacemakers in many animals are compound. In rodents, a two-oscillator model of the pacemaker composed of an evening (E) and a morning (M) oscillator has been proposed based on the phenomenon of "splitting" and bimodal activity peaks. The authors describe computer simulations of the pacemaker in tau mutant hamsters viewed as a system of mutually coupled E and M oscillators. These mutant animals exhibit normal type 1 PRCs when released into DD but make a transition to a type 0 PRC when held for many weeks in DD. The two-oscillator model describes particularly well some recent behavioral experiments on these hamsters. The authors sought to determine the relationships between oscillator amplitude, period, PRC, and activity duration through computer simulations. Two complementary approaches proved useful for analyzing weakly coupled oscillator systems. The authors adopted a "distinct oscillators" view when considering the component E and M oscillators and a "system" view when considering the system as a whole. For strongly coupled systems, only the system view is appropriate. The simulations lead the authors to two primary conjectures: (1) the total amplitude of the pacemaker system in tau mutant hamsters is less than in the wild-type animals, and (2) the coupling between the unit E and M oscillators is weakened during continuous exposure of hamsters to DD. As coupling strength decreases, activity duration (alpha) increases due to a greater phase difference between E and M. At the same time, the total amplitude of the system decreases, causing an increase in observable PRC amplitudes. Reduced coupling also increases the relative autonomy of the unit oscillators. The relatively autonomous phase shifts of E and M oscillators can account for both immediate compression and expansion of activity bands in tau mutant and wild-type hamsters subjected to light pulses.

  3. Individual-based modeling of ecological and evolutionary processes

    Science.gov (United States)

    DeAngelis, Donald L.; Mooij, Wolf M.

    2005-01-01

    Individual-based models (IBMs) allow the explicit inclusion of individual variation in greater detail than do classical differential-equation and difference-equation models. Inclusion of such variation is important for continued progress in ecological and evolutionary theory. We provide a conceptual basis for IBMs by describing five major types of individual variation in IBMs: spatial, ontogenetic, phenotypic, cognitive, and genetic. IBMs are now used in almost all subfields of ecology and evolutionary biology. We map those subfields and look more closely at selected key papers on fish recruitment, forest dynamics, sympatric speciation, metapopulation dynamics, maintenance of diversity, and species conservation. Theorists are currently divided on whether IBMs represent only a practical tool for extending classical theory to more complex situations, or whether individual-based theory represents a radically new research program. We feel that the tension between these two poles of thinking can be a source of creativity in ecology and evolutionary theory.

  4. Estimating true evolutionary distances under the DCJ model.

    Science.gov (United States)

    Lin, Yu; Moret, Bernard M E

    2008-07-01

    Modern techniques can yield the ordering and strandedness of genes on each chromosome of a genome; such data already exists for hundreds of organisms. The evolutionary mechanisms through which the set of the genes of an organism is altered and reordered are of great interest to systematists, evolutionary biologists, comparative genomicists and biomedical researchers. Perhaps the most basic concept in this area is that of evolutionary distance between two genomes: under a given model of genomic evolution, how many events most likely took place to account for the difference between the two genomes? We present a method to estimate the true evolutionary distance between two genomes under the 'double-cut-and-join' (DCJ) model of genome rearrangement, a model under which a single multichromosomal operation accounts for all genomic rearrangement events: inversion, transposition, translocation, block interchange and chromosomal fusion and fission. Our method relies on a simple structural characterization of a genome pair and is both analytically and computationally tractable. We provide analytical results to describe the asymptotic behavior of genomes under the DCJ model, as well as experimental results on a wide variety of genome structures to exemplify the very high accuracy (and low variance) of our estimator. Our results provide a tool for accurate phylogenetic reconstruction from multichromosomal gene rearrangement data as well as a theoretical basis for refinements of the DCJ model to account for biological constraints. All of our software is available in source form under GPL at http://lcbb.epfl.ch.

  5. An evolutionary behavioral model for decision making

    OpenAIRE

    Romero Lopez, Dr Oscar Javier

    2011-01-01

    For autonomous agents the problem of deciding what to do next becomes increasingly complex when acting in unpredictable and dynamic environments pursuing multiple and possibly conflicting goals. One of the most relevant behavior-based model that tries to deal with this problem is the one proposed by Maes, the Bbehavior Network model. This model proposes a set of behaviors as purposive perception-action units which are linked in a nonhierarchical network, and whose behavior selection process i...

  6. Evolutionary thinking in microeconomic models: prestige bias and market bubbles.

    Directory of Open Access Journals (Sweden)

    Adrian Viliami Bell

    Full Text Available Evolutionary models broadly support a number of social learning strategies likely important in economic behavior. Using a simple model of price dynamics, I show how prestige bias, or copying of famed (and likely successful individuals, influences price equilibria and investor disposition in a way that exacerbates or creates market bubbles. I discuss how integrating the social learning and demographic forces important in cultural evolution with economic models provides a fruitful line of inquiry into real-world behavior.

  7. Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model

    Directory of Open Access Journals (Sweden)

    Yuthavong Yongyuth

    2011-05-01

    Full Text Available Abstract Background The prevalence of drug resistance amongst the human malaria Plasmodium species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new Plasmodium falciparum dihydrofolate reductase (PfDHFR mutants that confer resistance to antifolate drugs is essential in the process of antifolate anti-malarial drug development. Methods A system to identify mutations in Pfdhfr gene that confer antifolate drug resistance using an animal Plasmodium parasite model was developed. By using error-prone PCR and Plasmodium transfection technologies, libraries of Pfdhfr mutant were generated and then episomally transfected to Plasmodium berghei parasites, from which pyrimethamine-resistant PfDHFR mutants were selected. Results The principal mutation found from this experiment was S108N, coincident with the first pyrimethamine-resistance mutation isolated from the field. A transgenic P. berghei, in which endogenous Pbdhfr allele was replaced with the mutant PfdhfrS108N, was generated and confirmed to have normal growth rate comparing to parental non-transgenic parasite and also confer resistance to pyrimethamine. Conclusion This study demonstrated the power of the transgenic P. berghei system to predict drug-resistant Pfdhfr mutations in an in vivo parasite/host setting. The system could be utilized for identification of possible novel drug-resistant mutants that could arise against new antifolate compounds and for prediction the evolution of resistance mutations.

  8. Asteroseismology of pulsating DA white dwarfs with fully evolutionary models

    Directory of Open Access Journals (Sweden)

    Althaus L.G.

    2013-03-01

    Full Text Available We present a new approach for asteroseismology of DA white dwarfs that consists in the employment of a large set of non-static, physically sound, fully evolutionary models representative of these stars. We already have applied this approach with success to pulsating PG1159 stars (GW Vir variables. Our white dwarf models, which cover a wide range of stellar masses, effective temperatures, and envelope thicknesses, are the result of fully evolutionary computations that take into account the complete history of the progenitor stars from the ZAMS. In particular, the models are characterized by self-consistent chemical structures from the centre to the surface, a crucial aspect of white dwarf asteroseismology. We apply this approach to an ensemble of 44 bright DAV (ZZ Ceti stars.

  9. Evolutionary model with genetics, aging, and knowledge

    Science.gov (United States)

    Bustillos, Armando Ticona; de Oliveira, Paulo Murilo

    2004-02-01

    We represent a process of learning by using bit strings, where 1 bits represent the knowledge acquired by individuals. Two ways of learning are considered: individual learning by trial and error, and social learning by copying knowledge from other individuals or from parents in the case of species with parental care. The age-structured bit string allows us to study how knowledge is accumulated during life and its influence over the genetic pool of a population after many generations. We use the Penna model to represent the genetic inheritance of each individual. In order to study how the accumulated knowledge influences the survival process, we include it to help individuals to avoid the various death situations. Modifications in the Verhulst factor do not show any special feature due to its random nature. However, by adding years to life as a function of the accumulated knowledge, we observe an improvement of the survival rates while the genetic fitness of the population becomes worse. In this latter case, knowledge becomes more important in the last years of life where individuals are threatened by diseases. Effects of offspring overprotection and differences between individual and social learning can also be observed. Sexual selection as a function of knowledge shows some effects when fidelity is imposed.

  10. Evolutionary model of the growth and size of firms

    Science.gov (United States)

    Kaldasch, Joachim

    2012-07-01

    The key idea of this model is that firms are the result of an evolutionary process. Based on demand and supply considerations the evolutionary model presented here derives explicitly Gibrat's law of proportionate effects as the result of the competition between products. Applying a preferential attachment mechanism for firms, the theory allows to establish the size distribution of products and firms. Also established are the growth rate and price distribution of consumer goods. Taking into account the characteristic property of human activities to occur in bursts, the model allows also an explanation of the size-variance relationship of the growth rate distribution of products and firms. Further the product life cycle, the learning (experience) curve and the market size in terms of the mean number of firms that can survive in a market are derived. The model also suggests the existence of an invariant of a market as the ratio of total profit to total revenue. The relationship between a neo-classic and an evolutionary view of a market is discussed. The comparison with empirical investigations suggests that the theory is able to describe the main stylized facts concerning the size and growth of firms.

  11. Radiation, ecology and the invalid LNT model: the evolutionary imperative.

    Science.gov (United States)

    Parsons, Peter A

    2006-09-27

    Metabolic and energetic efficiency, and hence fitness of organisms to survive, should be maximal in their habitats. This tenet of evolutionary biology invalidates the linear-no threshold (LNT) model for the risk consequences of environmental agents. Hormesis in response to selection for maximum metabolic and energetic efficiency, or minimum metabolic imbalance, to adapt to a stressed world dominated by oxidative stress should therefore be universal. Radiation hormetic zones extending substantially beyond common background levels, can be explained by metabolic interactions among multiple abiotic stresses. Demographic and experimental data are mainly in accord with this expectation. Therefore, non-linearity becomes the primary model for assessing risks from low-dose ionizing radiation. This is the evolutionary imperative upon which risk assessment for radiation should be based.

  12. Radiation, Ecology and the Invalid LNT Model: The Evolutionary Imperative

    OpenAIRE

    Parsons, Peter A.

    2006-01-01

    Metabolic and energetic efficiency, and hence fitness of organisms to survive, should be maximal in their habitats. This tenet of evolutionary biology invalidates the linear-nothreshold (LNT) model for the risk consequences of environmental agents. Hormesis in response to selection for maximum metabolic and energetic efficiency, or minimum metabolic imbalance, to adapt to a stressed world dominated by oxidative stress should therefore be universal. Radiation hormetic zones extending substanti...

  13. Evolutionary model of an anonymous consumer durable market

    Science.gov (United States)

    Kaldasch, Joachim

    2011-07-01

    An analytic model is presented that considers the evolution of a market of durable goods. The model suggests that after introduction goods spread always according to a Bass diffusion. However, this phase will be followed by a diffusion process for durable consumer goods governed by a variation-selection-reproduction mechanism and the growth dynamics can be described by a replicator equation. The theory suggests that products play the role of species in biological evolutionary models. It implies that the evolution of man-made products can be arranged into an evolutionary tree. The model suggests that each product can be characterized by its product fitness. The fitness space contains elements of both sites of the market, supply and demand. The unit sales of products with a higher product fitness compared to the mean fitness increase. Durables with a constant fitness advantage replace other goods according to a logistic law. The model predicts in particular that the mean price exhibits an exponential decrease over a long time period for durable goods. The evolutionary diffusion process is directly related to this price decline and is governed by Gompertz equation. Therefore it is denoted as Gompertz diffusion. Describing the aggregate sales as the sum of first, multiple and replacement purchase the product life cycle can be derived. Replacement purchase causes periodic variations of the sales determined by the finite lifetime of the good (Juglar cycles). The model suggests that both, Bass- and Gompertz diffusion may contribute to the product life cycle of a consumer durable. The theory contains the standard equilibrium view of a market as a special case. It depends on the time scale, whether an equilibrium or evolutionary description is more appropriate. The evolutionary framework is used to derive also the size, growth rate and price distribution of manufacturing business units. It predicts that the size distribution of the business units (products) is lognormal

  14. An Evolutionary Modelling Approach To Understanding The Factors Behind Plant Invasiveness And Community Susceptibility To Invasion

    DEFF Research Database (Denmark)

    Warren, John; Topping, Christopher John; James, Penri

    2011-01-01

    Ecologists have had limited success in understanding which introduced species may become invasive. An evolutionary model is used to investigate which traits are associated with invasiveness. Translocation experiments were simulated in which species were moved into similar but evolutionary younger...

  15. Dynamic and photometric evolutionary models of tidal tails and ripples

    International Nuclear Information System (INIS)

    Wallin, J.F.

    1989-01-01

    An investigation into the causes of star formation in tidal tails has been conducted using a restricted three-body dynamical model in conjunction with a broad-band photometric evolutionary code. In these models, regions of compression form inside the disk and along the tidal tail and tidal bridge. The effects these density changes have on the colors of the tidal features are examined with a broad-band photometric evolutionary code. A spiral galaxy population is synthesized and the effects of modest changes in the star formation rate are explored. Limits on the density changes needed to make detectable changes in the colors are calculated using a Schmidt (1959) law. These models suggest that the blue colors and knotty features observed in the tidal features of some galaxies result from increased rates of star formation induced by tidally produced density increases. Limitations of this model are discussed along with photometric evolutionary models based on the density evolution in the tails. The Lynds and Toomre (1976) interpretation of ring galaxies as the natural result of a nearly head-on collision between a disk galaxy and a companion galaxy has become widely accepted. Similarly, Quinn's (1984) interpretation of the shells in elliptical galaxies as the aftermath of the cannibalization of a low-mass companion has been quite successful in accounting for the observations. Restricted three-body calculations of high inclination, low impact parameter encounters demonstrate that the shell-like ripples observed in a number of disk galaxies can also be produced as collisional artifacts from internal oscillations much as in ring galaxies

  16. Yunnan-III models for evolutionary population synthesis

    Science.gov (United States)

    Zhang, F.; Li, L.; Han, Z.; Zhuang, Y.; Kang, X.

    2013-02-01

    We build the Yunnan-III evolutionary population synthesis (EPS) models by using the mesa stellar evolution code, BaSeL stellar spectra library and the initial mass functions (IMFs) of Kroupa and Salpeter, and present colours and integrated spectral energy distributions (ISEDs) of solar-metallicity stellar populations (SPs) in the range of 1 Myr to 15 Gyr. The main characteristic of the Yunnan-III EPS models is the usage of a set of self-consistent solar-metallicity stellar evolutionary tracks (the masses of stars are from 0.1 to 100 M⊙). This set of tracks is obtained by using the state-of-the-art mesa code. mesa code can evolve stellar models through thermally pulsing asymptotic giant branch (TP-AGB) phase for low- and intermediate-mass stars. By comparisons, we confirm that the inclusion of TP-AGB stars makes the V - K, V - J and V - R colours of SPs redder and the infrared flux larger at ages log(t/yr) ≳ 7.6 [the differences reach the maximum at log(t/yr) ˜ 8.6, ˜0.5-0.2 mag for colours, approximately two times for K-band flux]. We also find that the colour-evolution trends of Model with-TPAGB at intermediate and large ages are similar to those from the starburst99 code, which employs the Padova-AGB stellar library, BaSeL spectral library and the Kroupa IMF. At last, we compare the colours with the other EPS models comprising TP-AGB stars (such as CB07, M05, V10 and POPSTAR), and find that the B - V colour agrees with each other but the V-K colour shows a larger discrepancy among these EPS models [˜1 mag when 8 ≲ log(t/yr) ≲ 9]. The stellar evolutionary tracks, isochrones, colours and ISEDs can be obtained on request from the first author or from our website (http://www1.ynao.ac.cn/~zhangfh/). Using the isochrones, you can build your EPS models. Now the format of stellar evolutionary tracks is the same as that in the starburst99 code; you can put them into the starburst99 code and get the SP's results. Moreover, the colours involving other passbands

  17. Preference learning with evolutionary Multivariate Adaptive Regression Spline model

    DEFF Research Database (Denmark)

    Abou-Zleikha, Mohamed; Shaker, Noor; Christensen, Mads Græsbøll

    2015-01-01

    This paper introduces a novel approach for pairwise preference learning through combining an evolutionary method with Multivariate Adaptive Regression Spline (MARS). Collecting users' feedback through pairwise preferences is recommended over other ranking approaches as this method is more appealing...... for function approximation as well as being relatively easy to interpret. MARS models are evolved based on their efficiency in learning pairwise data. The method is tested on two datasets that collectively provide pairwise preference data of five cognitive states expressed by users. The method is analysed...

  18. Comparison of evolutionary algorithms in gene regulatory network model inference.

    LENUS (Irish Health Repository)

    2010-01-01

    ABSTRACT: BACKGROUND: The evolution of high throughput technologies that measure gene expression levels has created a data base for inferring GRNs (a process also known as reverse engineering of GRNs). However, the nature of these data has made this process very difficult. At the moment, several methods of discovering qualitative causal relationships between genes with high accuracy from microarray data exist, but large scale quantitative analysis on real biological datasets cannot be performed, to date, as existing approaches are not suitable for real microarray data which are noisy and insufficient. RESULTS: This paper performs an analysis of several existing evolutionary algorithms for quantitative gene regulatory network modelling. The aim is to present the techniques used and offer a comprehensive comparison of approaches, under a common framework. Algorithms are applied to both synthetic and real gene expression data from DNA microarrays, and ability to reproduce biological behaviour, scalability and robustness to noise are assessed and compared. CONCLUSIONS: Presented is a comparison framework for assessment of evolutionary algorithms, used to infer gene regulatory networks. Promising methods are identified and a platform for development of appropriate model formalisms is established.

  19. An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

    Science.gov (United States)

    Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

    2017-11-22

    Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

  20. A network growth model based on the evolutionary ultimatum game

    International Nuclear Information System (INIS)

    Deng, L L; Zhou, G G; Cai, J H; Wang, C; Tang, W S

    2012-01-01

    In this paper, we provide a network growth model with incorporation into the ultimatum game dynamics. The network grows on the basis of the payoff-oriented preferential attachment mechanism, where a new node is added into the network and attached preferentially to nodes with higher payoffs. The interplay between the network growth and the game dynamics gives rise to quite interesting dynamical behaviors. Simulation results show the emergence of altruistic behaviors in the ultimatum game, which is affected by the growing network structure. Compared with the static counterpart case, the levels of altruistic behaviors are promoted. The corresponding strategy distributions and wealth distributions are also presented to further demonstrate the strategy evolutionary dynamics. Subsequently, we turn to the topological properties of the evolved network, by virtue of some statistics. The most studied characteristic path length and the clustering coefficient of the network are shown to indicate their small-world effect. Then the degree distributions are analyzed to clarify the interplay of structure and evolutionary dynamics. In particular, the difference between our growth network and the static counterpart is revealed. To explain clearly the evolved networks, the rich-club ordering and the assortative mixing coefficient are exploited to reveal the degree correlation. (paper)

  1. Mapping the Conformation Space of Wildtype and Mutant H-Ras with a Memetic, Cellular, and Multiscale Evolutionary Algorithm.

    Directory of Open Access Journals (Sweden)

    Rudy Clausen

    2015-09-01

    Full Text Available An important goal in molecular biology is to understand functional changes upon single-point mutations in proteins. Doing so through a detailed characterization of structure spaces and underlying energy landscapes is desirable but continues to challenge methods based on Molecular Dynamics. In this paper we propose a novel algorithm, SIfTER, which is based instead on stochastic optimization to circumvent the computational challenge of exploring the breadth of a protein's structure space. SIfTER is a data-driven evolutionary algorithm, leveraging experimentally-available structures of wildtype and variant sequences of a protein to define a reduced search space from where to efficiently draw samples corresponding to novel structures not directly observed in the wet laboratory. The main advantage of SIfTER is its ability to rapidly generate conformational ensembles, thus allowing mapping and juxtaposing landscapes of variant sequences and relating observed differences to functional changes. We apply SIfTER to variant sequences of the H-Ras catalytic domain, due to the prominent role of the Ras protein in signaling pathways that control cell proliferation, its well-studied conformational switching, and abundance of documented mutations in several human tumors. Many Ras mutations are oncogenic, but detailed energy landscapes have not been reported until now. Analysis of SIfTER-computed energy landscapes for the wildtype and two oncogenic variants, G12V and Q61L, suggests that these mutations cause constitutive activation through two different mechanisms. G12V directly affects binding specificity while leaving the energy landscape largely unchanged, whereas Q61L has pronounced, starker effects on the landscape. An implementation of SIfTER is made available at http://www.cs.gmu.edu/~ashehu/?q=OurTools. We believe SIfTER is useful to the community to answer the question of how sequence mutations affect the function of a protein, when there is an

  2. Kernel Method Based Human Model for Enhancing Interactive Evolutionary Optimization

    Science.gov (United States)

    Zhao, Qiangfu; Liu, Yong

    2015-01-01

    A fitness landscape presents the relationship between individual and its reproductive success in evolutionary computation (EC). However, discrete and approximate landscape in an original search space may not support enough and accurate information for EC search, especially in interactive EC (IEC). The fitness landscape of human subjective evaluation in IEC is very difficult and impossible to model, even with a hypothesis of what its definition might be. In this paper, we propose a method to establish a human model in projected high dimensional search space by kernel classification for enhancing IEC search. Because bivalent logic is a simplest perceptual paradigm, the human model is established by considering this paradigm principle. In feature space, we design a linear classifier as a human model to obtain user preference knowledge, which cannot be supported linearly in original discrete search space. The human model is established by this method for predicting potential perceptual knowledge of human. With the human model, we design an evolution control method to enhance IEC search. From experimental evaluation results with a pseudo-IEC user, our proposed model and method can enhance IEC search significantly. PMID:25879050

  3. A Study On Traditional And Evolutionary Software Development Models

    Directory of Open Access Journals (Sweden)

    Kamran Rasheed

    2017-07-01

    Full Text Available Today Computing technologies are becoming the pioneers of the organizations and helpful in individual functionality i.e. added to computing device we need to add softwares. Set of instruction or computer program is known as software. The development of software is done through some traditional or some new or evolutionary models. Software development is becoming a key and a successful business nowadays. Without software all hardware is useless. Some collective steps that are performed in the development of these are known as Software development life cycle SDLC. There are some adaptive and predictive models for developing software. Predictive mean already known like WATERFALL Spiral Prototype and V-shaped models while Adaptive model include agile Scrum. All methodologies of both adaptive and predictive have their own procedure and steps. Predictive are Static and Adaptive are dynamic mean change cannot be made to the predictive while adaptive have the capability of changing. The purpose of this study is to get familiar with all these and discuss their uses and steps of development. This discussion will be helpful in deciding which model they should use in which circumstance and what are the development step including in each model.

  4. Characterizing Phase Transitions in a Model of Neutral Evolutionary Dynamics

    Science.gov (United States)

    Scott, Adam; King, Dawn; Bahar, Sonya

    2013-03-01

    An evolutionary model was recently introduced for sympatric, phenotypic evolution over a variable fitness landscape with assortative mating (Dees & Bahar 2010). Organisms in the model are described by coordinates in a two-dimensional phenotype space, born at random coordinates with limited variation from their parents as determined by a mutation parameter, mutability. The model has been extended to include both neutral evolution and asexual reproduction in Scott et al (submitted). It has been demonstrated that a second order, non-equilibrium phase transition occurs for the temporal dynamics as the mutability is varied, for both the original model and for neutral conditions. This transition likely belongs to the directed percolation universality class. In contrast, the spatial dynamics of the model shows characteristics of an ordinary percolation phase transition. Here, we characterize the phase transitions exhibited by this model by determining critical exponents for the relaxation times, characteristic lengths, and cluster (species) mass distributions. Missouri Research Board; J.S. McDonnell Foundation

  5. How altruism works: An evolutionary model of supply networks

    Science.gov (United States)

    Ge, Zehui; Zhang, Zi-Ke; Lü, Linyuan; Zhou, Tao; Xi, Ning

    2012-02-01

    Recently, supply networks have attracted increasing attention from the scientific community. However, it lacks serious consideration of social preference in Supply Chain Management. In this paper, we develop an evolutionary decision-making model to characterize the effects of suppliers' altruism in supply networks, and find that the performances of both suppliers and supply chains are improved by introducing the role of altruism. Furthermore, an interesting and reasonable phenomenon is discovered that the suppliers' and whole network's profits do not change monotonously with suppliers' altruistic preference, η, but reach the best at η=0.6 and η=0.4, respectively. This work may shed some light on the in-depth understanding of the effects of altruism for both research and commercial applications.

  6. Evolutionary neural network modeling for software cumulative failure time prediction

    International Nuclear Information System (INIS)

    Tian Liang; Noore, Afzel

    2005-01-01

    An evolutionary neural network modeling approach for software cumulative failure time prediction based on multiple-delayed-input single-output architecture is proposed. Genetic algorithm is used to globally optimize the number of the delayed input neurons and the number of neurons in the hidden layer of the neural network architecture. Modification of Levenberg-Marquardt algorithm with Bayesian regularization is used to improve the ability to predict software cumulative failure time. The performance of our proposed approach has been compared using real-time control and flight dynamic application data sets. Numerical results show that both the goodness-of-fit and the next-step-predictability of our proposed approach have greater accuracy in predicting software cumulative failure time compared to existing approaches

  7. Evolutionary model of the subdwarf binary system LB3459

    International Nuclear Information System (INIS)

    Paczynski, B.; Dearborn, D.S.

    1980-01-01

    An evolutionary model is proposed for the eclipsing binary system LB 3459 (=CPD-60 0 389 = HDE 269696). The two stars are hot subdwarfs with degenerate helium cores, hydrogen burning shell sources and low mass hydrogen rich envelopes. The system probably evolved through two common envelope phases. After the first such phase it might look like the semi-detached binary AS Eri. Soon after the second common envelope phase the system might look like UU Sge, an eclipsing binary nucleus of a planetary nebula. The present mass of the optical (spectroscopic) primary is probably close to 0.24 solar mass, and the predicted radial velocity amplitude of the primary is about 150 km/s. The optical secondary should be hotter and bolometrically brighter, with a mass of 0.32 solar mass. The primary eclipse is an occultation. (author)

  8. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

    Directory of Open Access Journals (Sweden)

    Sara eAmorim-Vaz

    2015-05-01

    Full Text Available The aim of the present study was to identify C. albicans transcription factors (TF involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens quantified in kidneys. Mutants of unannotated genes which generated a kidney fungal burden significantly different from that of wild-type were selected and individually examined in G. mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25 % of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects, a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching fungal burden phenotypes were observed in 50 % of the cases, highlighting the bias due to host effects. In contrast, 33.4 % concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the pool effect. After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adaptation.

  9. Basic emotions and adaptation. A computational and evolutionary model.

    Science.gov (United States)

    Pacella, Daniela; Ponticorvo, Michela; Gigliotta, Onofrio; Miglino, Orazio

    2017-01-01

    The core principles of the evolutionary theories of emotions declare that affective states represent crucial drives for action selection in the environment and regulated the behavior and adaptation of natural agents in ancestrally recurrent situations. While many different studies used autonomous artificial agents to simulate emotional responses and the way these patterns can affect decision-making, few are the approaches that tried to analyze the evolutionary emergence of affective behaviors directly from the specific adaptive problems posed by the ancestral environment. A model of the evolution of affective behaviors is presented using simulated artificial agents equipped with neural networks and physically inspired on the architecture of the iCub humanoid robot. We use genetic algorithms to train populations of virtual robots across generations, and investigate the spontaneous emergence of basic emotional behaviors in different experimental conditions. In particular, we focus on studying the emotion of fear, therefore the environment explored by the artificial agents can contain stimuli that are safe or dangerous to pick. The simulated task is based on classical conditioning and the agents are asked to learn a strategy to recognize whether the environment is safe or represents a threat to their lives and select the correct action to perform in absence of any visual cues. The simulated agents have special input units in their neural structure whose activation keep track of their actual "sensations" based on the outcome of past behavior. We train five different neural network architectures and then test the best ranked individuals comparing their performances and analyzing the unit activations in each individual's life cycle. We show that the agents, regardless of the presence of recurrent connections, spontaneously evolved the ability to cope with potentially dangerous environment by collecting information about the environment and then switching their behavior

  10. Statistical optimization for enhanced yields of probiotic Bacillus coagulans and its phage resistant mutants followed by kinetic modelling of the process.

    Science.gov (United States)

    Pandey, Kavita R; Joshi, Chetan; Vakil, Babu V

    2016-01-01

    Probiotics are microorganisms which when administered in adequate amounts confer health benefits to the host. A leading pharmaceutical company producing Bacillus coagulans as a probiotic was facing the problem of recurring phage attacks. Two mutants viz. B. co PIII and B. co MIII that were isolated as phage resistant mutants after UV irradiation and MMS treatment of phage sensitive B. coagulans parental culture were characterized at functional and molecular level and were noted to have undergone interesting genetic changes. The non-specific genetic alterations induced by mutagenesis can also lead to alterations in cell performance. Hence, in the current study the parental strain and the two mutants were selected for shake flask optimization. Plackett-Burman design was used to select the significant culture variables affecting biomass production. Evolutionary operation method was applied for further optimization. The study showed wide variations in the nutritional requirements of phage resistant mutants, post exposure to mutagens. An increment of 150, 134 and 152 % was observed in the biomass productions of B. coagulans (parental type) and mutants B.co PIII and B.co MIII respectively, compared to the yield from one-factor-at-a-time technique. Using Logistic and modified Leudeking-Piret equations, biomass accumulation and substrate utilization efficiency of the bioprocess were determined. The experimental data was in agreement with the results predicted by statistical analysis and modelling. The developed model may be useful for controlling the growth and substrate consumption kinetics in large scale fermentation using B. coagulans .

  11. Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Chao Liu

    2015-08-01

    Full Text Available Apolipoprotein C-II (APOC2 is an obligatory activator of lipoprotein lipase. Human patients with APOC2 deficiency display severe hypertriglyceridemia while consuming a normal diet, often manifesting xanthomas, lipemia retinalis and pancreatitis. Hypertriglyceridemia is also an important risk factor for development of cardiovascular disease. Animal models to study hypertriglyceridemia are limited, with no Apoc2-knockout mouse reported. To develop a genetic model of hypertriglyceridemia, we generated an apoc2 mutant zebrafish characterized by the loss of Apoc2 function. apoc2 mutants show decreased plasma lipase activity and display chylomicronemia and severe hypertriglyceridemia, which closely resemble the phenotype observed in human patients with APOC2 deficiency. The hypertriglyceridemia in apoc2 mutants is rescued by injection of plasma from wild-type zebrafish or by injection of a human APOC2 mimetic peptide. Consistent with a previous report of a transient apoc2 knockdown, apoc2 mutant larvae have a minor delay in yolk consumption and angiogenesis. Furthermore, apoc2 mutants fed a normal diet accumulate lipid and lipid-laden macrophages in the vasculature, which resemble early events in the development of human atherosclerotic lesions. In addition, apoc2 mutant embryos show ectopic overgrowth of pancreas. Taken together, our data suggest that the apoc2 mutant zebrafish is a robust and versatile animal model to study hypertriglyceridemia and the mechanisms involved in the pathogenesis of associated human diseases.

  12. Marmosets as model species in neuroscience and evolutionary anthropology.

    Science.gov (United States)

    Burkart, Judith M; Finkenwirth, Christa

    2015-04-01

    Marmosets are increasingly used as model species by both neuroscientists and evolutionary anthropologists, but with a different rationale for doing so. Whereas neuroscientists stress that marmosets share many cognitive traits with humans due to common descent, anthropologists stress those traits shared with marmosets - and callitrichid monkeys in general - due to convergent evolution, as a consequence of the cooperative breeding system that characterizes both humans and callitrichids. Similarities in socio-cognitive abilities due to convergence, rather than homology, raise the question whether these similarities also extend to the proximate regulatory mechanisms, which is particularly relevant for neuroscientific investigations. In this review, we first provide an overview of the convergent adaptations to cooperative breeding at the psychological and cognitive level in primates, which bear important implications for our understanding of human cognitive evolution. In the second part, we zoom in on two of these convergent adaptations, proactive prosociality and social learning, and compare their proximate regulation in marmosets and humans with regard to oxytocin and cognitive top down regulation. Our analysis suggests considerable similarity in these regulatory mechanisms presumably because the convergent traits emerged due to small motivational changes that define how pre-existing cognitive mechanisms are quantitatively combined. This finding reconciles the prima facie contradictory rationale for using marmosets as high priority model species in neuroscience and anthropology. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  13. The Zipf Law revisited: An evolutionary model of emerging classification

    Energy Technology Data Exchange (ETDEWEB)

    Levitin, L.B. [Boston Univ., MA (United States); Schapiro, B. [TINA, Brandenburg (Germany); Perlovsky, L. [NRC, Wakefield, MA (United States)

    1996-12-31

    Zipf`s Law is a remarkable rank-frequency relationship observed in linguistics (the frequencies of the use of words are approximately inversely proportional to their ranks in the decreasing frequency order) as well as in the behavior of many complex systems of surprisingly different nature. We suggest an evolutionary model of emerging classification of objects into classes corresponding to concepts and denoted by words. The evolution of the system is derived from two basic assumptions: first, the probability to recognize an object as belonging to a known class is proportional to the number of objects in this class already recognized, and, second, there exists a small probability to observe an object that requires creation of a new class ({open_quotes}mutation{close_quotes} that gives birth to a new {open_quotes}species{close_quotes}). It is shown that the populations of classes in such a system obey the Zipf Law provided that the rate of emergence of new classes is small. The model leads also to the emergence of a second-tier structure of {open_quotes}super-classes{close_quotes} - groups of classes with almost equal populations.

  14. Gnarled-trunk evolutionary model of influenza A virus hemagglutinin.

    Directory of Open Access Journals (Sweden)

    Kimihito Ito

    Full Text Available Human influenza A viruses undergo antigenic changes with gradual accumulation of amino acid substitutions on the hemagglutinin (HA molecule. A strong antigenic mismatch between vaccine and epidemic strains often requires the replacement of influenza vaccines worldwide. To establish a practical model enabling us to predict the future direction of the influenza virus evolution, relative distances of amino acid sequences among past epidemic strains were analyzed by multidimensional scaling (MDS. We found that human influenza viruses have evolved along a gnarled evolutionary pathway with an approximately constant curvature in the MDS-constructed 3D space. The gnarled pathway indicated that evolution on the trunk favored multiple substitutions at the same amino acid positions on HA. The constant curvature was reasonably explained by assuming that the rate of amino acid substitutions varied from one position to another according to a gamma distribution. Furthermore, we utilized the estimated parameters of the gamma distribution to predict the amino acid substitutions on HA in subsequent years. Retrospective prediction tests for 12 years from 1997 to 2009 showed that 70% of actual amino acid substitutions were correctly predicted, and that 45% of predicted amino acid substitutions have been actually observed. Although it remains unsolved how to predict the exact timing of antigenic changes, the present results suggest that our model may have the potential to recognize emerging epidemic strains.

  15. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Directory of Open Access Journals (Sweden)

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  16. Invisible hand effect in an evolutionary minority game model

    Science.gov (United States)

    Sysi-Aho, Marko; Saramäki, Jari; Kaski, Kimmo

    2005-03-01

    In this paper, we study the properties of a minority game with evolution realized by using genetic crossover to modify fixed-length decision-making strategies of agents. Although the agents in this evolutionary game act selfishly by trying to maximize their own performances only, it turns out that the whole society will eventually be rewarded optimally. This “invisible hand” effect is what Adam Smith over two centuries ago expected to take place in the context of free market mechanism. However, this behaviour of the society of agents is realized only under idealized conditions, where all agents are utilizing the same efficient evolutionary mechanism. If on the other hand part of the agents are adaptive, but not evolutionary, the system does not reach optimum performance, which is also the case if part of the evolutionary agents form a uniformly acting “cartel”.

  17. A methodology for evaluation of parent-mutant competition using a generalized non-linear ecosystem model

    Science.gov (United States)

    Raymond L. Czaplewski

    1973-01-01

    A generalized, non-linear population dynamics model of an ecosystem is used to investigate the direction of selective pressures upon a mutant by studying the competition between parent and mutant populations. The model has the advantages of considering selection as operating on the phenotype, of retaining the interaction of the mutant population with the ecosystem as a...

  18. Basic emotions and adaptation. A computational and evolutionary model.

    Directory of Open Access Journals (Sweden)

    Daniela Pacella

    Full Text Available The core principles of the evolutionary theories of emotions declare that affective states represent crucial drives for action selection in the environment and regulated the behavior and adaptation of natural agents in ancestrally recurrent situations. While many different studies used autonomous artificial agents to simulate emotional responses and the way these patterns can affect decision-making, few are the approaches that tried to analyze the evolutionary emergence of affective behaviors directly from the specific adaptive problems posed by the ancestral environment. A model of the evolution of affective behaviors is presented using simulated artificial agents equipped with neural networks and physically inspired on the architecture of the iCub humanoid robot. We use genetic algorithms to train populations of virtual robots across generations, and investigate the spontaneous emergence of basic emotional behaviors in different experimental conditions. In particular, we focus on studying the emotion of fear, therefore the environment explored by the artificial agents can contain stimuli that are safe or dangerous to pick. The simulated task is based on classical conditioning and the agents are asked to learn a strategy to recognize whether the environment is safe or represents a threat to their lives and select the correct action to perform in absence of any visual cues. The simulated agents have special input units in their neural structure whose activation keep track of their actual "sensations" based on the outcome of past behavior. We train five different neural network architectures and then test the best ranked individuals comparing their performances and analyzing the unit activations in each individual's life cycle. We show that the agents, regardless of the presence of recurrent connections, spontaneously evolved the ability to cope with potentially dangerous environment by collecting information about the environment and then

  19. Economic modeling using evolutionary algorithms : the effect of binary encoding of strategies

    NARCIS (Netherlands)

    Waltman, L.R.; Eck, van N.J.; Dekker, Rommert; Kaymak, U.

    2011-01-01

    We are concerned with evolutionary algorithms that are employed for economic modeling purposes. We focus in particular on evolutionary algorithms that use a binary encoding of strategies. These algorithms, commonly referred to as genetic algorithms, are popular in agent-based computational economics

  20. Cash Management Policies By Evolutionary Models: A Comparison Using The MILLER-ORR Model

    Directory of Open Access Journals (Sweden)

    Marcelo Botelho da Costa Moraes

    2013-10-01

    Full Text Available This work aims to apply genetic algorithms (GA and particle swarm optimization (PSO to managing cash balance, comparing performance results between computational models and the Miller-Orr model. Thus, the paper proposes the application of computational evolutionary models to minimize the total cost of cash balance maintenance, obtaining the parameters for a cash management policy, using assumptions presented in the literature, considering the cost of maintenance and opportunity for cost of cash. For such, we developed computational experiments from cash flows simulated to implement the algorithms. For a control purpose, an algorithm has been developed that uses the Miller-Orr model defining the lower bound parameter, which is not obtained by the original model. The results indicate that evolutionary algorithms present better results than the Miller-Orr model, with prevalence for PSO algorithm in results.

  1. Strengths and Weaknesses of McNamara's Evolutionary Psychological Model of Dreaming

    Directory of Open Access Journals (Sweden)

    Sandra Olliges

    2010-10-01

    Full Text Available This article includes a brief overview of McNamara's (2004 evolutionary model of dreaming. The strengths and weaknesses of this model are then evaluated in terms of its consonance with measurable neurological and biological properties of dreaming, its fit within the tenets of evolutionary theories of dreams, and its alignment with evolutionary concepts of cooperation and spirituality. McNamara's model focuses primarily on dreaming that occurs during rapid eye movement (REM sleep; therefore this article also focuses on REM dreaming.

  2. Modeling evolutionary games in populations with demographic structure

    DEFF Research Database (Denmark)

    Li, Xiang-Yi; Giaimo, Stefano; Baudisch, Annette

    2015-01-01

    interactions, but usually omits life history and the demographic structure of the population. Here we show how an integration of both aspects can substantially alter the underlying evolutionary dynamics. We study the replicator dynamics of strategy interactions in life stage structured populations. Individuals...

  3. Mutant mice: experimental organisms as materialised models in biomedicine.

    Science.gov (United States)

    Huber, Lara; Keuck, Lara K

    2013-09-01

    Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. An evolutionary model of bounded rationality and intelligence.

    Directory of Open Access Journals (Sweden)

    Thomas J Brennan

    Full Text Available BACKGROUND: Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia-it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. METHODS AND FINDINGS: Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. CONCLUSIONS: Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that

  5. An evolutionary model of bounded rationality and intelligence.

    Science.gov (United States)

    Brennan, Thomas J; Lo, Andrew W

    2012-01-01

    Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia-it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that arise from natural selection. The key to understanding which types of

  6. Micro-Tom Tomato as an Alternative Plant Model System: Mutant Collection and Efficient Transformation.

    Science.gov (United States)

    Shikata, Masahito; Ezura, Hiroshi

    2016-01-01

    Tomato is a model plant for fruit development, a unique feature that classical model plants such as Arabidopsis and rice do not have. The tomato genome was sequenced in 2012 and tomato is becoming very popular as an alternative system for plant research. Among many varieties of tomato, Micro-Tom has been recognized as a model cultivar for tomato research because it shares some key advantages with Arabidopsis including its small size, short life cycle, and capacity to grow under fluorescent lights at a high density. Mutants and transgenic plants are essential materials for functional genomics research, and therefore, the availability of mutant resources and methods for genetic transformation are key tools to facilitate tomato research. Here, we introduce the Micro-Tom mutant database "TOMATOMA" and an efficient transformation protocol for Micro-Tom.

  7. More efficient evolutionary strategies for model calibration with watershed model for demonstration

    Science.gov (United States)

    Baggett, J. S.; Skahill, B. E.

    2008-12-01

    Evolutionary strategies allow automatic calibration of more complex models than traditional gradient based approaches, but they are more computationally intensive. We present several efficiency enhancements for evolution strategies, many of which are not new, but when combined have been shown to dramatically decrease the number of model runs required for calibration of synthetic problems. To reduce the number of expensive model runs we employ a surrogate objective function for an adaptively determined fraction of the population at each generation (Kern et al., 2006). We demonstrate improvements to the adaptive ranking strategy that increase its efficiency while sacrificing little reliability and further reduce the number of model runs required in densely sampled parts of parameter space. Furthermore, we include a gradient individual in each generation that is usually not selected when the search is in a global phase or when the derivatives are poorly approximated, but when selected near a smooth local minimum can dramatically increase convergence speed (Tahk et al., 2007). Finally, the selection of the gradient individual is used to adapt the size of the population near local minima. We show, by incorporating these enhancements into the Covariance Matrix Adaption Evolution Strategy (CMAES; Hansen, 2006), that their synergetic effect is greater than their individual parts. This hybrid evolutionary strategy exploits smooth structure when it is present but degrades to an ordinary evolutionary strategy, at worst, if smoothness is not present. Calibration of 2D-3D synthetic models with the modified CMAES requires approximately 10%-25% of the model runs of ordinary CMAES. Preliminary demonstration of this hybrid strategy will be shown for watershed model calibration problems. Hansen, N. (2006). The CMA Evolution Strategy: A Comparing Review. In J.A. Lozano, P. Larrañga, I. Inza and E. Bengoetxea (Eds.). Towards a new evolutionary computation. Advances in estimation of

  8. The Sequences of 1504 Mutants in the Model Rice Variety Kitaake Facilitate Rapid Functional Genomic Studies.

    Science.gov (United States)

    Li, Guotian; Jain, Rashmi; Chern, Mawsheng; Pham, Nikki T; Martin, Joel A; Wei, Tong; Schackwitz, Wendy S; Lipzen, Anna M; Duong, Phat Q; Jones, Kyle C; Jiang, Liangrong; Ruan, Deling; Bauer, Diane; Peng, Yi; Barry, Kerrie W; Schmutz, Jeremy; Ronald, Pamela C

    2017-06-01

    The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitate functional genomic analysis. To this end, we generated and sequenced a fast-neutron-induced mutant population in the model rice cultivar Kitaake ( Oryza sativa ssp japonica ), which completes its life cycle in 9 weeks. We sequenced 1504 mutant lines at 45-fold coverage and identified 91,513 mutations affecting 32,307 genes, i.e., 58% of all rice genes. We detected an average of 61 mutations per line. Mutation types include single-base substitutions, deletions, insertions, inversions, translocations, and tandem duplications. We observed a high proportion of loss-of-function mutations. We identified an inversion affecting a single gene as the causative mutation for the short-grain phenotype in one mutant line. This result reveals the usefulness of the resource for efficient, cost-effective identification of genes conferring specific phenotypes. To facilitate public access to this genetic resource, we established an open access database called KitBase that provides access to sequence data and seed stocks. This population complements other available mutant collections and gene-editing technologies. This work demonstrates how inexpensive next-generation sequencing can be applied to generate a high-density catalog of mutations. © 2017 American Society of Plant Biologists. All rights reserved.

  9. Building v/s Exploring Models: Comparing Learning of Evolutionary Processes through Agent-based Modeling

    Science.gov (United States)

    Wagh, Aditi

    Two strands of work motivate the three studies in this dissertation. Evolutionary change can be viewed as a computational complex system in which a small set of rules operating at the individual level result in different population level outcomes under different conditions. Extensive research has documented students' difficulties with learning about evolutionary change (Rosengren et al., 2012), particularly in terms of levels slippage (Wilensky & Resnick, 1999). Second, though building and using computational models is becoming increasingly common in K-12 science education, we know little about how these two modalities compare. This dissertation adopts agent-based modeling as a representational system to compare these modalities in the conceptual context of micro-evolutionary processes. Drawing on interviews, Study 1 examines middle-school students' productive ways of reasoning about micro-evolutionary processes to find that the specific framing of traits plays a key role in whether slippage explanations are cued. Study 2, which was conducted in 2 schools with about 150 students, forms the crux of the dissertation. It compares learning processes and outcomes when students build their own models or explore a pre-built model. Analysis of Camtasia videos of student pairs reveals that builders' and explorers' ways of accessing rules, and sense-making of observed trends are of a different character. Builders notice rules through available blocks-based primitives, often bypassing their enactment while explorers attend to rules primarily through the enactment. Moreover, builders' sense-making of observed trends is more rule-driven while explorers' is more enactment-driven. Pre and posttests reveal that builders manifest a greater facility with accessing rules, providing explanations manifesting targeted assembly. Explorers use rules to construct explanations manifesting non-targeted assembly. Interviews reveal varying degrees of shifts away from slippage in both

  10. Prediction of stock markets by the evolutionary mix-game model

    Science.gov (United States)

    Chen, Fang; Gou, Chengling; Guo, Xiaoqian; Gao, Jieping

    2008-06-01

    This paper presents the efforts of using the evolutionary mix-game model, which is a modified form of the agent-based mix-game model, to predict financial time series. Here, we have carried out three methods to improve the original mix-game model by adding the abilities of strategy evolution to agents, and then applying the new model referred to as the evolutionary mix-game model to forecast the Shanghai Stock Exchange Composite Index. The results show that these modifications can improve the accuracy of prediction greatly when proper parameters are chosen.

  11. Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model

    OpenAIRE

    Tipsuwan, Wachiraporn; Srichairatanakool, Somdet; Kamchonwongpaisan, Sumalee; Yuthavong, Yongyuth; Uthaipibull, Chairat

    2011-01-01

    Abstract Background The prevalence of drug resistance amongst the human malaria Plasmodium species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new Plasmodium falciparum dihydrofolate reductase (PfDHFR) mutants that confer resistance to antifolate drugs is essential in the process of...

  12. Evolutionary modelling of the macro-economic impacts of catastrophic flood events

    NARCIS (Netherlands)

    Safarzynska, K.E.; Brouwer, R.; Hofkes, M.

    2013-01-01

    This paper examines the possible contribution of evolutionary economics to macro-economic modelling of flood impacts to provide guidance for future economic risk modelling. Most macro-economic models start from a neoclassical economic perspective and focus on equilibrium outcomes, either in a static

  13. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

    2015-11-01

    Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

    Science.gov (United States)

    Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

    2017-03-07

    The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole

  15. Not just a theory--the utility of mathematical models in evolutionary biology.

    Directory of Open Access Journals (Sweden)

    Maria R Servedio

    2014-12-01

    Full Text Available Progress in science often begins with verbal hypotheses meant to explain why certain biological phenomena exist. An important purpose of mathematical models in evolutionary research, as in many other fields, is to act as “proof-of-concept” tests of the logic in verbal explanations, paralleling the way in which empirical data are used to test hypotheses. Because not all subfields of biology use mathematics for this purpose, misunderstandings of the function of proof-of-concept modeling are common. In the hope of facilitating communication, we discuss the role of proof-of-concept modeling in evolutionary biology.

  16. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

    Science.gov (United States)

    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  17. Social change and increasing of bipolar disorders: an evolutionary model.

    Science.gov (United States)

    Carta, Mauro Giovanni

    2013-01-01

    The objective of this paper is to see if behaviours defined as pathological and maladjusted in certain contexts may produce adaptive effects in other contexts, especially if they occur in attenuated form. Interactions between environment and behaviour are studied from an evolutionary standpoint in an attempt to understand how new attitudes emerge in an evolving context. Narrative review. Following an historical examination of how the description of depression in Western society has changed, we examine a series of studies performed in areas where great changes have taken place as well as research on emigration from Sardinia in the 1960s and 70s and immigration to Sardinia in the 1990s. If we postulate that mood disorders are on the increase and that the epidemic began in the 17th century with the "English malady", we must suppose that at least the "light" forms have an adaptive advantage, otherwise the expansion of the disorder would have been self-limiting. "Compulsive hyper-responsabilization", as well as explorative behaviours, may represent a base for adaptation in certain conditions of social change. The social emphasis in individualism and responsibility may have changed not only the frequency, but also the phenomenology of mood disorders particularly the increases in bipolar disorders. From the sociobiological standpoint the conditions that may favour "subthreshold" bipolar or depressive features are to be considered in relation to the contextual role of gender and the different risks of the two disorders in males and females.

  18. Pragmatic quality metrics for evolutionary software development models

    Science.gov (United States)

    Royce, Walker

    1990-01-01

    Due to the large number of product, project, and people parameters which impact large custom software development efforts, measurement of software product quality is a complex undertaking. Furthermore, the absolute perspective from which quality is measured (customer satisfaction) is intangible. While we probably can't say what the absolute quality of a software product is, we can determine the relative quality, the adequacy of this quality with respect to pragmatic considerations, and identify good and bad trends during development. While no two software engineers will ever agree on an optimum definition of software quality, they will agree that the most important perspective of software quality is its ease of change. We can call this flexibility, adaptability, or some other vague term, but the critical characteristic of software is that it is soft. The easier the product is to modify, the easier it is to achieve any other software quality perspective. This paper presents objective quality metrics derived from consistent lifecycle perspectives of rework which, when used in concert with an evolutionary development approach, can provide useful insight to produce better quality per unit cost/schedule or to achieve adequate quality more efficiently. The usefulness of these metrics is evaluated by applying them to a large, real world, Ada project.

  19. Aggregate meta-models for evolutionary multiobjective and many-objective optimization

    Czech Academy of Sciences Publication Activity Database

    Pilát, Martin; Neruda, Roman

    Roč. 116, 20 September (2013), s. 392-402 ISSN 0925-2312 R&D Projects: GA ČR GAP202/11/1368 Institutional support: RVO:67985807 Keywords : evolutionary algorithms * multiobjective optimization * many-objective optimization * surrogate models * meta-models * memetic algorithm Subject RIV: IN - Informatics, Computer Science Impact factor: 2.005, year: 2013

  20. An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy

    DEFF Research Database (Denmark)

    Bach, L.A.; Bentzen, S.M.; Alsner, Jan

    2001-01-01

    Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent...

  1. Pseudorandom numbers: evolutionary models in image processing, biology, and nonlinear dynamic systems

    Science.gov (United States)

    Yaroslavsky, Leonid P.

    1996-11-01

    We show that one can treat pseudo-random generators, evolutionary models of texture images, iterative local adaptive filters for image restoration and enhancement and growth models in biology and material sciences in a unified way as special cases of dynamic systems with a nonlinear feedback.

  2. Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts.

    Science.gov (United States)

    Andley, Usha P; Goldman, Joshua W

    2016-01-01

    Knock-in mice provide useful models of congenital and age-related cataracts caused by α-crystallin mutations. R49C αA-crystallin and R120G αB-crystallin mutations are linked with hereditary cataracts. Knock-in αA-R49C+/- heterozygotes develop cataracts by 1-2months, whereas homozygote mice have cataracts at birth. The R49C mutation drastically reduces lens protein water solubility and causes cell death in knock-in mouse lenses. Mutant crystallin cannot function as a chaperone, which leads to protein aggregation and lens opacity. Protein aggregation disrupts the lens fiber cell structure and normal development and causes cell death in epithelial and fiber cells. We determined what aspects of the wild-type phenotype are age-dependently altered in the mutant lens. Wild-type, heterozygote (αA-R49C+/-), and homozygote (αA-R49C+/+) mouse lenses were assessed pre- and postnatally for lens morphology (electron microscopy, immunohistochemistry), and autophagy or unfolded protein response markers (immunoblotting). Morphology was altered by embryonic day 17 in R49C+/+ lenses; R49C+/- lens morphology was unaffected at this stage. Active autophagy in the lens epithelium of mutant lenses was indicated by the presence of autophagosomes using electron microscopy. Protein p62 levels, which are degraded specifically by autophagy, increased in αA-R49C mutant versus wild-type lenses, suggesting autophagy inhibition in the mutant lenses. The unfolded protein response marker XBP-1 was upregulated in adult lenses of αB-R120G+/+ mice, suggesting its role in lens opacification. Mutated crystallins alter lens morphology, autophagy, and stress responses. Therapeutic modulation of autophagic pathways may improve protein degradation in cataractous lenses and reduce lens opacity. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Estimating the ratios of the stationary distribution values for Markov chains modeling evolutionary algorithms.

    Science.gov (United States)

    Mitavskiy, Boris; Cannings, Chris

    2009-01-01

    The evolutionary algorithm stochastic process is well-known to be Markovian. These have been under investigation in much of the theoretical evolutionary computing research. When the mutation rate is positive, the Markov chain modeling of an evolutionary algorithm is irreducible and, therefore, has a unique stationary distribution. Rather little is known about the stationary distribution. In fact, the only quantitative facts established so far tell us that the stationary distributions of Markov chains modeling evolutionary algorithms concentrate on uniform populations (i.e., those populations consisting of a repeated copy of the same individual). At the same time, knowing the stationary distribution may provide some information about the expected time it takes for the algorithm to reach a certain solution, assessment of the biases due to recombination and selection, and is of importance in population genetics to assess what is called a "genetic load" (see the introduction for more details). In the recent joint works of the first author, some bounds have been established on the rates at which the stationary distribution concentrates on the uniform populations. The primary tool used in these papers is the "quotient construction" method. It turns out that the quotient construction method can be exploited to derive much more informative bounds on ratios of the stationary distribution values of various subsets of the state space. In fact, some of the bounds obtained in the current work are expressed in terms of the parameters involved in all the three main stages of an evolutionary algorithm: namely, selection, recombination, and mutation.

  4. Genome-wide investigation reveals high evolutionary rates in annual model plants.

    Science.gov (United States)

    Yue, Jia-Xing; Li, Jinpeng; Wang, Dan; Araki, Hitoshi; Tian, Dacheng; Yang, Sihai

    2010-11-09

    Rates of molecular evolution vary widely among species. While significant deviations from molecular clock have been found in many taxa, effects of life histories on molecular evolution are not fully understood. In plants, annual/perennial life history traits have long been suspected to influence the evolutionary rates at the molecular level. To date, however, the number of genes investigated on this subject is limited and the conclusions are mixed. To evaluate the possible heterogeneity in evolutionary rates between annual and perennial plants at the genomic level, we investigated 85 nuclear housekeeping genes, 10 non-housekeeping families, and 34 chloroplast genes using the genomic data from model plants including Arabidopsis thaliana and Medicago truncatula for annuals and grape (Vitis vinifera) and popular (Populus trichocarpa) for perennials. According to the cross-comparisons among the four species, 74-82% of the nuclear genes and 71-97% of the chloroplast genes suggested higher rates of molecular evolution in the two annuals than those in the two perennials. The significant heterogeneity in evolutionary rate between annuals and perennials was consistently found both in nonsynonymous sites and synonymous sites. While a linear correlation of evolutionary rates in orthologous genes between species was observed in nonsynonymous sites, the correlation was weak or invisible in synonymous sites. This tendency was clearer in nuclear genes than in chloroplast genes, in which the overall evolutionary rate was small. The slope of the regression line was consistently lower than unity, further confirming the higher evolutionary rate in annuals at the genomic level. The higher evolutionary rate in annuals than in perennials appears to be a universal phenomenon both in nuclear and chloroplast genomes in the four dicot model plants we investigated. Therefore, such heterogeneity in evolutionary rate should result from factors that have genome-wide influence, most likely those

  5. Computational Modeling of Teaching and Learning through Application of Evolutionary Algorithms

    Directory of Open Access Journals (Sweden)

    Richard Lamb

    2015-09-01

    Full Text Available Within the mind, there are a myriad of ideas that make sense within the bounds of everyday experience, but are not reflective of how the world actually exists; this is particularly true in the domain of science. Classroom learning with teacher explanation are a bridge through which these naive understandings can be brought in line with scientific reality. The purpose of this paper is to examine how the application of a Multiobjective Evolutionary Algorithm (MOEA can work in concert with an existing computational-model to effectively model critical-thinking in the science classroom. An evolutionary algorithm is an algorithm that iteratively optimizes machine learning based computational models. The research question is, does the application of an evolutionary algorithm provide a means to optimize the Student Task and Cognition Model (STAC-M and does the optimized model sufficiently represent and predict teaching and learning outcomes in the science classroom? Within this computational study, the authors outline and simulate the effect of teaching on the ability of a “virtual” student to solve a Piagetian task. Using the Student Task and Cognition Model (STAC-M a computational model of student cognitive processing in science class developed in 2013, the authors complete a computational experiment which examines the role of cognitive retraining on student learning. Comparison of the STAC-M and the STAC-M with inclusion of the Multiobjective Evolutionary Algorithm shows greater success in solving the Piagetian science-tasks post cognitive retraining with the Multiobjective Evolutionary Algorithm. This illustrates the potential uses of cognitive and neuropsychological computational modeling in educational research. The authors also outline the limitations and assumptions of computational modeling.

  6. The circling mutant Pcdh15roda is a new mouse model for hearing loss.

    Science.gov (United States)

    Torres, Adriana Amorim; Rzadzinska, Agnieszka K; Ribeiro, Andrea Frozino; Silva, Daniel Almeida da Silva E; Guénet, Jean-Louis; Massironi, Sílvia Maria Gomes; Godard, Ana Lúcia Brunialti

    2013-01-01

    Mouse mutagenesis is a key tool for studying gene function and several mutant alleles have been described and constitute mouse models for human hereditary diseases. Genetic hearing loss represents over 50% of all hearing loss cases in children and, due to the heterogeneity of the disorder, there is still a demand for the isolation and characterization of new genes and alleles. Here we report phenotypic and molecular characterization of a new mouse model for hereditary hearing loss. The mutant rodador, isolated by Massironi and colleagues in 2006, presents an autosomal recessive disorder characterized by deafness and balance dysfunction associated with abnormal stereocilia in the inner ear. The mutation was mapped to mouse chromosome 10, and characterization of the gene Pcdh15 revealed an AT-to-GC transition in intron 23 of mutant animals. The alteration led to the switch of a dinucleotide ApA for ApG, creating a novel intronic acceptor splice site, which leads to incorporation of eight intronic bases into the processed mRNA and alteration of the downstream reading frame. In silico analysis indicated that the mutated protein is truncated and lacks two cadherin domains, and the transmembrane and cytoplasmic domains. Real Time PCR analyses revealed a significantly reduced Pcdh15 mRNA level in the brain of mutant mice, which might be due to the mechanism of non-sense mediated decay. In man, mutations in the orthologue PCDH15 cause non-syndromic deafness and Usher Syndrome Type 1F, a genetic disorder characterized by hearing loss and retinitis pigmentosa. Rodador mouse constitutes a new model for studying deafness in these conditions and may help in the comprehension of the pathogeneses of the disease, as well as of the mechanisms involved in the morphogenesis and function of inner ear stereocilia. This is a new ENU-induced allele and the first isolated in a BALB/c background. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Genetic Models in Evolutionary Game Theory: The Evolution of Altruism

    NARCIS (Netherlands)

    Rubin, Hannah

    2015-01-01

    While prior models of the evolution of altruism have assumed that organisms reproduce asexually, this paper presents a model of the evolution of altruism for sexually reproducing organisms using Hardy–Weinberg dynamics. In this model, the presence of reciprocal altruists allows the population to

  8. GALEV evolutionary synthesis models – I. Code, input physics and web

    NARCIS (Netherlands)

    Kotulla, R.; Fritze, U.; Weilbacher, P.; Anders, P.

    2009-01-01

    GALEV (GALaxy EVolution) evolutionary synthesis models describe the evolution of stellar populations in general, of star clusters as well as of galaxies, both in terms of resolved stellar populations and of integrated light properties over cosmological time-scales of ≥13 Gyr from the onset of star

  9. Evolutionary ecology in silico: Does mathematical modelling help

    Indian Academy of Sciences (India)

    Keywords. Computer simulation; extinction; food web; population dynamics; speciation; unified model ... Moreover, because of the availability of sufficiently fast computers, it has become possible to carry out detailed computer simulations of these models. For the sake of completeness and to put these recent developments ...

  10. Bipartite Graphs as Models of Population Structures in Evolutionary Multiplayer Games

    Science.gov (United States)

    Peña, Jorge; Rochat, Yannick

    2012-01-01

    By combining evolutionary game theory and graph theory, “games on graphs” study the evolutionary dynamics of frequency-dependent selection in population structures modeled as geographical or social networks. Networks are usually represented by means of unipartite graphs, and social interactions by two-person games such as the famous prisoner’s dilemma. Unipartite graphs have also been used for modeling interactions going beyond pairwise interactions. In this paper, we argue that bipartite graphs are a better alternative to unipartite graphs for describing population structures in evolutionary multiplayer games. To illustrate this point, we make use of bipartite graphs to investigate, by means of computer simulations, the evolution of cooperation under the conventional and the distributed N-person prisoner’s dilemma. We show that several implicit assumptions arising from the standard approach based on unipartite graphs (such as the definition of replacement neighborhoods, the intertwining of individual and group diversity, and the large overlap of interaction neighborhoods) can have a large impact on the resulting evolutionary dynamics. Our work provides a clear example of the importance of construction procedures in games on graphs, of the suitability of bigraphs and hypergraphs for computational modeling, and of the importance of concepts from social network analysis such as centrality, centralization and bipartite clustering for the understanding of dynamical processes occurring on networked population structures. PMID:22970237

  11. The Tangled Nature Model of evolutionary dynamics reconsidered

    DEFF Research Database (Denmark)

    Andersen, Christian Walther; Sibani, Paolo

    2016-01-01

    The Tangled Nature Model of biological and cultural evolution features interacting agents which compete for limited resources and reproduce in an error prone fashion and at a rate depending on the `tangle' of interactions they maintain with others. The set of interactions linking a TNM individual....... To bring out the structural and dynamical effects of trait inheritance , we introduce and numerically analyze a family of TNM models where a positive integer $K$ parametrises correlations between the interactions of an agent and those of its mutated offspring. For $K=1$ a single point mutation randomizes...

  12. Hypermedia Genes An Evolutionary Perspective on Concepts, Models, and Architectures

    CERN Document Server

    Guimarães, Nuno

    2009-01-01

    The design space of information services evolved from seminal works through a set of prototypical hypermedia systems and matured in open and widely accessible web-based systems. The original concepts of hypermedia systems are now expressed in different forms and shapes. The first works on hypertext invented the term itself, laid out the foundational concept of association or link, and highlighted navigation as the core paradigm for the future information systems. The first engineered systems demonstrated architectural requirements and models and fostered the emergence of the conceptual model r

  13. Evolutionary models of early-type contact binary SV Centauri

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Y; Saio, H [Tohoku Univ., Sendai (Japan). Faculty of Science; Sugimoto, Daiichiro

    1978-12-01

    Models of the early-type contact binary system SV Centauri are computed with a binary-star evolution program. The effects of mass exchange, i.e., the effects of mass acceptance as well as mass loss, are properly included. With the initial masses of the component stars as 12.4 and 8.0 M sub(solar mass), the following observed configurations are well reproduced; the component stars are definitely in contact and the rate of mass exchange is 4 x 10/sup -4/ M sub(solar mass)yr/sup -1/. The more massive component is less luminous and has a lower effective temperature. Such features are also reproduced quantitatively. Agreement of the computed models with observation indicates that the binary system SV Cen is actually in the phase of rapid mass exchange preceding the mass-ratio reversal.

  14. Study on system dynamics of evolutionary mix-game models

    Science.gov (United States)

    Gou, Chengling; Guo, Xiaoqian; Chen, Fang

    2008-11-01

    Mix-game model is ameliorated from an agent-based MG model, which is used to simulate the real financial market. Different from MG, there are two groups of agents in Mix-game: Group 1 plays a majority game and Group 2 plays a minority game. These two groups of agents have different bounded abilities to deal with historical information and to count their own performance. In this paper, we modify Mix-game model by assigning the evolution abilities to agents: if the winning rates of agents are smaller than a threshold, they will copy the best strategies the other agent has; and agents will repeat such evolution at certain time intervals. Through simulations this paper finds: (1) the average winning rates of agents in Group 1 and the mean volatilities increase with the increases of the thresholds of Group 1; (2) the average winning rates of both groups decrease but the mean volatilities of system increase with the increase of the thresholds of Group 2; (3) the thresholds of Group 2 have greater impact on system dynamics than the thresholds of Group 1; (4) the characteristics of system dynamics under different time intervals of strategy change are similar to each other qualitatively, but they are different quantitatively; (5) As the time interval of strategy change increases from 1 to 20, the system behaves more and more stable and the performances of agents in both groups become better also.

  15. A Self-adaptive Dynamic Evaluation Model for Diabetes Mellitus, Based on Evolutionary Strategies

    Directory of Open Access Journals (Sweden)

    An-Jiang Lu

    2016-03-01

    Full Text Available In order to evaluate diabetes mellitus objectively and accurately, this paper builds a self-adaptive dynamic evaluation model for diabetes mellitus, based on evolutionary strategies. First of all, on the basis of a formalized description of the evolutionary process of diabetes syndromes, using a state transition function, it judges whether a disease is evolutionary, through an excitation parameter. It then, provides evidence for the rebuilding of the evaluation index system. After that, by abstracting and rebuilding the composition of evaluation indexes, it makes use of a heuristic algorithm to determine the composition of the evolved evaluation index set of diabetes mellitus, It then, calculates the weight of each index in the evolved evaluation index set of diabetes mellitus by building a dependency matrix and realizes the self-adaptive dynamic evaluation of diabetes mellitus under an evolutionary environment. Using this evaluation model, it is possible to, quantify all kinds of diagnoses and treatment experiences of diabetes and finally to adopt ideal diagnoses and treatment measures for different patients with diabetics.

  16. A dynamic parking charge optimal control model under perspective of commuters' evolutionary game behavior

    Science.gov (United States)

    Lin, XuXun; Yuan, PengCheng

    2018-01-01

    In this research we consider commuters' dynamic learning effect by modeling the trip mode choice behavior from a new perspective of dynamic evolutionary game theory. We explore the behavior pattern of different types of commuters and study the evolution path and equilibrium properties under different traffic conditions. We further establish a dynamic parking charge optimal control (referred to as DPCOC) model to alter commuters' trip mode choice while minimizing the total social cost. Numerical tests show. (1) Under fixed parking fee policy, the evolutionary results are completely decided by the travel time and the only method for public transit induction is to increase the parking charge price. (2) Compared with fixed parking fee policy, DPCOC policy proposed in this research has several advantages. Firstly, it can effectively turn the evolutionary path and evolutionary stable strategy to a better situation while minimizing the total social cost. Secondly, it can reduce the sensitivity of trip mode choice behavior to traffic congestion and improve the ability to resist interferences and emergencies. Thirdly, it is able to control the private car proportion to a stable state and make the trip behavior more predictable for the transportation management department. The research results can provide theoretical basis and decision-making references for commuters' mode choice prediction, dynamic setting of urban parking charge prices and public transit induction.

  17. An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

    Directory of Open Access Journals (Sweden)

    P Martin Sander

    Full Text Available Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM. This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism". Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

  18. An Evolutionary Cascade Model for Sauropod Dinosaur Gigantism - Overview, Update and Tests

    Science.gov (United States)

    Sander, P. Martin

    2013-01-01

    Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades (“Reproduction”, “Feeding”, “Head and neck”, “Avian-style lung”, and “Metabolism”). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait “Very high body mass”. Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size. PMID:24205267

  19. An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

    Science.gov (United States)

    Sander, P Martin

    2013-01-01

    Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism"). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

  20. An evolutionary model for protein-coding regions with conserved RNA structure

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Forsberg, Roald; Meyer, Irmtraud Margret

    2004-01-01

    in the RNA structure. The overlap of these fundamental dependencies is sufficient to cause "contagious" context dependencies which cascade across many nucleotide sites. Such large-scale dependencies challenge the use of traditional phylogenetic models in evolutionary inference because they explicitly assume...... components of traditional phylogenetic models. We applied this to a data set of full-genome sequences from the hepatitis C virus where five RNA structures are mapped within the coding region. This allowed us to partition the effects of selection on different structural elements and to test various hypotheses......Here we present a model of nucleotide substitution in protein-coding regions that also encode the formation of conserved RNA structures. In such regions, apparent evolutionary context dependencies exist, both between nucleotides occupying the same codon and between nucleotides forming a base pair...

  1. Multiparty Evolutionary Game Model in Coal Mine Safety Management and Its Application

    Directory of Open Access Journals (Sweden)

    Rongwu Lu

    2018-01-01

    Full Text Available Coal mine safety management involves many interested parties and there are complex relationships between them. According to game theory, a multiparty evolutionary game model is established to analyze the selection of strategies. Then, a simplified three-party model is taken as an example to carry out detailed analysis and solution. Based on stability theory of dynamics system and phase diagram analysis, this article studies replicator dynamics of the evolutionary model to make an optimization analysis of the behaviors of those interested parties and the adjustment mechanism of safety management policies and decisions. The results show how the charge of supervision of government department and inspection of coal mine enterprise impact the efficiency of safety management and the effect of constraint measures and incentive and other measures in safety management.

  2. Prediction of strong earthquake motions on rock surface using evolutionary process models

    International Nuclear Information System (INIS)

    Kameda, H.; Sugito, M.

    1984-01-01

    Stochastic process models are developed for prediction of strong earthquake motions for engineering design purposes. Earthquake motions with nonstationary frequency content are modeled by using the concept of evolutionary processes. Discussion is focused on the earthquake motions on bed rocks which are important for construction of nuclear power plants in seismic regions. On this basis, two earthquake motion prediction models are developed, one (EMP-IB Model) for prediction with given magnitude and epicentral distance, and the other (EMP-IIB Model) to account for the successive fault ruptures and the site location relative to the fault of great earthquakes. (Author) [pt

  3. EvoBuild: A Quickstart Toolkit for Programming Agent-Based Models of Evolutionary Processes

    Science.gov (United States)

    Wagh, Aditi; Wilensky, Uri

    2018-04-01

    Extensive research has shown that one of the benefits of programming to learn about scientific phenomena is that it facilitates learning about mechanisms underlying the phenomenon. However, using programming activities in classrooms is associated with costs such as requiring additional time to learn to program or students needing prior experience with programming. This paper presents a class of programming environments that we call quickstart: Environments with a negligible threshold for entry into programming and a modest ceiling. We posit that such environments can provide benefits of programming for learning without incurring associated costs for novice programmers. To make this claim, we present a design-based research study conducted to compare programming models of evolutionary processes with a quickstart toolkit with exploring pre-built models of the same processes. The study was conducted in six seventh grade science classes in two schools. Students in the programming condition used EvoBuild, a quickstart toolkit for programming agent-based models of evolutionary processes, to build their NetLogo models. Students in the exploration condition used pre-built NetLogo models. We demonstrate that although students came from a range of academic backgrounds without prior programming experience, and all students spent the same number of class periods on the activities including the time students took to learn programming in this environment, EvoBuild students showed greater learning about evolutionary mechanisms. We discuss the implications of this work for design research on programming environments in K-12 science education.

  4. TOWARD A GLOBAL EVOLUTIONARY MODEL OF PROTOPLANETARY DISKS

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xue-Ning, E-mail: xbai@cfa.harvard.edu [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden St., MS-51, Cambridge, MA 02138 (United States)

    2016-04-20

    A global picture of the evolution  of protoplanetary disks (PPDs) is key to understanding almost every aspect of planet formation, where standard α-disk models have been continually employed for their simplicity. In the meantime, disk mass loss has been conventionally attributed to photoevaporation, which controls disk dispersal. However, a paradigm shift toward accretion driven by magnetized disk winds has taken place in recent years, thanks to studies of non-ideal magnetohydrodynamic effects in PPDs. I present a framework of global PPD evolution aiming to incorporate these advances, highlighting the role of wind-driven accretion and wind mass loss. Disk evolution is found to be largely dominated by wind-driven processes, and viscous spreading is suppressed. The timescale of disk evolution is controlled primarily by the amount of external magnetic flux threading the disks, and how rapidly the disk loses the flux. Rapid disk dispersal can be achieved if the disk is able to hold most of its magnetic flux during the evolution. In addition, because wind launching requires a sufficient level of ionization at the disk surface (mainly via external far-UV (FUV) radiation), wind kinematics is also affected by the FUV penetration depth and disk geometry. For a typical disk lifetime of a few million years, the disk loses approximately the same amount of mass through the wind as through accretion onto the protostar, and most of the wind mass loss proceeds from the outer disk via a slow wind. Fractional wind mass loss increases with increasing disk lifetime. Significant wind mass loss likely substantially enhances the dust-to-gas mass ratio and promotes planet formation.

  5. TOWARD A GLOBAL EVOLUTIONARY MODEL OF PROTOPLANETARY DISKS

    International Nuclear Information System (INIS)

    Bai, Xue-Ning

    2016-01-01

    A global picture of the evolution  of protoplanetary disks (PPDs) is key to understanding almost every aspect of planet formation, where standard α-disk models have been continually employed for their simplicity. In the meantime, disk mass loss has been conventionally attributed to photoevaporation, which controls disk dispersal. However, a paradigm shift toward accretion driven by magnetized disk winds has taken place in recent years, thanks to studies of non-ideal magnetohydrodynamic effects in PPDs. I present a framework of global PPD evolution aiming to incorporate these advances, highlighting the role of wind-driven accretion and wind mass loss. Disk evolution is found to be largely dominated by wind-driven processes, and viscous spreading is suppressed. The timescale of disk evolution is controlled primarily by the amount of external magnetic flux threading the disks, and how rapidly the disk loses the flux. Rapid disk dispersal can be achieved if the disk is able to hold most of its magnetic flux during the evolution. In addition, because wind launching requires a sufficient level of ionization at the disk surface (mainly via external far-UV (FUV) radiation), wind kinematics is also affected by the FUV penetration depth and disk geometry. For a typical disk lifetime of a few million years, the disk loses approximately the same amount of mass through the wind as through accretion onto the protostar, and most of the wind mass loss proceeds from the outer disk via a slow wind. Fractional wind mass loss increases with increasing disk lifetime. Significant wind mass loss likely substantially enhances the dust-to-gas mass ratio and promotes planet formation

  6. USING ECO-EVOLUTIONARY INDIVIDUAL-BASED MODELS TO INVESTIGATE SPATIALLY-DEPENDENT PROCESSES IN CONSERVATION GENETICS

    Science.gov (United States)

    Eco-evolutionary population simulation models are powerful new forecasting tools for exploring management strategies for climate change and other dynamic disturbance regimes. Additionally, eco-evo individual-based models (IBMs) are useful for investigating theoretical feedbacks ...

  7. THE APPLICATION OF AN EVOLUTIONARY ALGORITHM TO THE OPTIMIZATION OF A MESOSCALE METEOROLOGICAL MODEL

    Energy Technology Data Exchange (ETDEWEB)

    Werth, D.; O' Steen, L.

    2008-02-11

    We show that a simple evolutionary algorithm can optimize a set of mesoscale atmospheric model parameters with respect to agreement between the mesoscale simulation and a limited set of synthetic observations. This is illustrated using the Regional Atmospheric Modeling System (RAMS). A set of 23 RAMS parameters is optimized by minimizing a cost function based on the root mean square (rms) error between the RAMS simulation and synthetic data (observations derived from a separate RAMS simulation). We find that the optimization can be efficient with relatively modest computer resources, thus operational implementation is possible. The optimization efficiency, however, is found to depend strongly on the procedure used to perturb the 'child' parameters relative to their 'parents' within the evolutionary algorithm. In addition, the meteorological variables included in the rms error and their weighting are found to be an important factor with respect to finding the global optimum.

  8. Generator Approach to Evolutionary Optimization of Catalysts and its Integration with Surrogate Modeling

    Czech Academy of Sciences Publication Activity Database

    Holeňa, Martin; Linke, D.; Rodemerck, U.

    2011-01-01

    Roč. 159, č. 1 (2011), s. 84-95 ISSN 0920-5861 R&D Projects: GA ČR GA201/08/0802 Institutional research plan: CEZ:AV0Z10300504 Keywords : optimization of catalytic materials * evolutionary optimization * surrogate modeling * artificial neural networks * multilayer perceptron * regression boosting Subject RIV: IN - Informatics, Computer Science Impact factor: 3.407, year: 2011

  9. Understanding herding based on a co-evolutionary model for strategy and game structure

    International Nuclear Information System (INIS)

    Wang, Tao; Huang, Keke; Cheng, Yuan; Zheng, Xiaoping

    2015-01-01

    Highlights: •We model herding effect in emergency from perspective of evolutionary game theory. •Rational subpopulation survives only when the game parameter is significantly large. •Herding effect may arise if the relative rewarding for rational agents is small. •Increasing the relative rewarding for rational agents will prevent herding effect. •The evolution result is unstable if the game parameter approaches critical points. -- Abstract: So far, there has been no conclusion on the mechanism for herding, which is often discussed in the academia. Assuming escaping behavior of individuals in emergency is rational rather than out of panic according to recent findings in social psychology, we investigate the behavioral evolution of large crowds from the perspective of evolutionary game theory. Specifically, evolution of the whole population divided into two subpopulations, namely the co-evolution of strategy and game structure, is numerically simulated based on the game theoretical models built and the evolutionary rule designed, and a series of phenomena including extinction of one subpopulation and herding effect are predicted in the proposed framework. Furthermore, if the rewarding for rational agents becomes significantly larger than that for emotional ones, herding effect will disappear. It is exciting that some phase transition points with interesting properties for the system can be found. In addition, our model framework is able to explain the fact that it is difficult for mavericks to prevail in society. The current results of this work will be helpful in understanding and restraining herding effect in real life

  10. Linear and evolutionary polynomial regression models to forecast coastal dynamics: Comparison and reliability assessment

    Science.gov (United States)

    Bruno, Delia Evelina; Barca, Emanuele; Goncalves, Rodrigo Mikosz; de Araujo Queiroz, Heithor Alexandre; Berardi, Luigi; Passarella, Giuseppe

    2018-01-01

    In this paper, the Evolutionary Polynomial Regression data modelling strategy has been applied to study small scale, short-term coastal morphodynamics, given its capability for treating a wide database of known information, non-linearly. Simple linear and multilinear regression models were also applied to achieve a balance between the computational load and reliability of estimations of the three models. In fact, even though it is easy to imagine that the more complex the model, the more the prediction improves, sometimes a "slight" worsening of estimations can be accepted in exchange for the time saved in data organization and computational load. The models' outcomes were validated through a detailed statistical, error analysis, which revealed a slightly better estimation of the polynomial model with respect to the multilinear model, as expected. On the other hand, even though the data organization was identical for the two models, the multilinear one required a simpler simulation setting and a faster run time. Finally, the most reliable evolutionary polynomial regression model was used in order to make some conjecture about the uncertainty increase with the extension of extrapolation time of the estimation. The overlapping rate between the confidence band of the mean of the known coast position and the prediction band of the estimated position can be a good index of the weakness in producing reliable estimations when the extrapolation time increases too much. The proposed models and tests have been applied to a coastal sector located nearby Torre Colimena in the Apulia region, south Italy.

  11. The environmental zero-point problem in evolutionary reaction norm modeling.

    Science.gov (United States)

    Ergon, Rolf

    2018-04-01

    There is a potential problem in present quantitative genetics evolutionary modeling based on reaction norms. Such models are state-space models, where the multivariate breeder's equation in some form is used as the state equation that propagates the population state forward in time. These models use the implicit assumption of a constant reference environment, in many cases set to zero. This zero-point is often the environment a population is adapted to, that is, where the expected geometric mean fitness is maximized. Such environmental reference values follow from the state of the population system, and they are thus population properties. The environment the population is adapted to, is, in other words, an internal population property, independent of the external environment. It is only when the external environment coincides with the internal reference environment, or vice versa, that the population is adapted to the current environment. This is formally a result of state-space modeling theory, which is an important theoretical basis for evolutionary modeling. The potential zero-point problem is present in all types of reaction norm models, parametrized as well as function-valued, and the problem does not disappear when the reference environment is set to zero. As the environmental reference values are population characteristics, they ought to be modeled as such. Whether such characteristics are evolvable is an open question, but considering the complexity of evolutionary processes, such evolvability cannot be excluded without good arguments. As a straightforward solution, I propose to model the reference values as evolvable mean traits in their own right, in addition to other reaction norm traits. However, solutions based on an evolvable G matrix are also possible.

  12. Modelling Hepatitis B Virus Antiviral Therapy and Drug Resistant Mutant Strains

    Science.gov (United States)

    Bernal, Julie; Dix, Trevor; Allison, Lloyd; Bartholomeusz, Angeline; Yuen, Lilly

    Despite the existence of vaccines, the Hepatitis B virus (HBV) is still a serious global health concern. HBV targets liver cells. It has an unusual replication process involving an RNA pre-genome that the reverse transcriptase domain of the viral polymerase protein translates into viral DNA. The reverse transcription process is error prone and together with the high replication rates of the virus, allows the virus to exist as a heterogeneous population of mutants, known as a quasispecies, that can adapt and become resistant to antiviral therapy. This study presents an individual-based model of HBV inside an artificial liver, and associated blood serum, undergoing antiviral therapy. This model aims to provide insights into the evolution of the HBV quasispecies and the individual contribution of HBV mutations in the outcome of therapy.

  13. Numerical Simulation of Entropy Growth for a Nonlinear Evolutionary Model of Random Markets

    Directory of Open Access Journals (Sweden)

    Mahdi Keshtkar

    2016-01-01

    Full Text Available In this communication, the generalized continuous economic model for random markets is revisited. In this model for random markets, agents trade by pairs and exchange their money in a random and conservative way. They display the exponential wealth distribution as asymptotic equilibrium, independently of the effectiveness of the transactions and of the limitation of the total wealth. In the current work, entropy of mentioned model is defined and then some theorems on entropy growth of this evolutionary problem are given. Furthermore, the entropy increasing by simulation on some numerical examples is verified.

  14. Species packing in eco-evolutionary models of seasonally fluctuating environments.

    Science.gov (United States)

    Kremer, Colin T; Klausmeier, Christopher A

    2017-09-01

    As ecology and evolution become ever more entwined, many areas of ecological theory are being re-examined. Eco-evolutionary analyses of classic coexistence mechanisms are yielding new insights into the structure and stability of communities. We examine fluctuation-dependent coexistence models, identifying communities that are both ecologically and evolutionarily stable. Members of these communities possess distinct environmental preferences, revealing widespread patterns of limiting similarity. This regularity leads to consistent changes in the structure of communities across fluctuation regimes. However, at high amplitudes, subtle differences in the form of fluctuations dramatically affect the collapse of communities. We also show that identical fluctuations can support multiple evolutionarily stable communities - a novel example of alternative stable states within eco-evolutionary systems. Consequently, the configuration of communities will depend on historical contingencies, including details of the adaptive process. Integrating evolution into the study of coexistence offers new insights, while enriching our understanding of ecology. © 2017 John Wiley & Sons Ltd/CNRS.

  15. Evolutionary Game Model Study of Construction Green Supply Chain Management under the Government Intervention

    Science.gov (United States)

    Xing, Yuanzhi; Deng, Xiaoyi

    2017-11-01

    The paper first has defined the concepts of green supply chain management and evolution game theory, and pointed out the characteristics of green supply chain management in construction. The main participants and key links of the construction green supply chain management are determined by constructing the organization framework. This paper established the evolutionary game model between construction enterprises and recycling enterprises for the green supply chain closed-loop structure. The waste recycling evolutionary stability equilibrium solution is obtained to explore the principle and effective scope of government policy intervention. This paper put forward the relevant countermeasures to the green supply chain management in construction recycling stage from the government point of view. The conclusion has reference value and guidance to the final product construction enterprises, recycling enterprises and the government during green supply chain.

  16. Tables and intercomparisons of evolutionary sequences of models for massive stars

    International Nuclear Information System (INIS)

    Chin, Chaowen; Stothers, R.B.

    1990-01-01

    Tables of evolutionary sequences of models for massive stars have been prepared for a variety of physical input parameters that are normally treated as free. These parameters include the interior convective mixing scheme, the mixing length in the outer convective envelope, the rate of stellar-wind mass loss, the initial stellar mass, and the initial chemical composition. Ranges of specified initial mass and initial chemical composition are M = 10-120 solar masses, Xe = 0.602-0.739, and Ze = 0.021-0.044. The tables cover evolution of the star from the ZAMS to either the end of core H burning or the end of core He burning. Differences among the evolutionary tracks are illustrated primarily in terms of the interior mixing scheme, since the amount and timing of stellar wind mass loss are still very uncertain for initial masses above about 30 solar masses. 52 refs

  17. An evolutionary model of cooperation, fairness and altruistic punishment in public good games.

    Science.gov (United States)

    Hetzer, Moritz; Sornette, Didier

    2013-01-01

    We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment.

  18. An evolutionary model of cooperation, fairness and altruistic punishment in public good games.

    Directory of Open Access Journals (Sweden)

    Moritz Hetzer

    Full Text Available We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment.

  19. Evolutionary Stages of e-Tailors and Retailers: Firm Value Determinants Model

    OpenAIRE

    Jae K. Lee; Heegoo Kang; Hoe K. Lee; Han S. Lee

    2002-01-01

    We have studied the evolutionary stages of pure e-tailers, click & mortar (C&M) and brick & mortar (B&M) retailers for three points of time: June 1999, June 2000, and June 2001. To evaluate the dynamic stages of e-tailing business as an innovative venture, we propose four stages: exploration, breakeven, growth, and maturity. The stages are measured by the impact of revenue and income on the firm value, and a regression model is adopted to formulate the model. To empirically examine the stages...

  20. A Study on Standard Competition with Network Effect Based on Evolutionary Game Model

    Science.gov (United States)

    Wang, Ye; Wang, Bingdong; Li, Kangning

    Owing to networks widespread in modern society, standard competition with network effect is now endowed with new connotation. This paper aims to study the impact of network effect on standard competition; it is organized in the mode of "introduction-model setup-equilibrium analysis-conclusion". Starting from a well-structured model of evolutionary game, it is then extended to a dynamic analysis. This article proves both theoretically and empirically that whether or not a standard can lead the market trends depends on the utility it would bring, and the author also discusses some advisable strategies revolving around the two factors of initial position and border break.

  1. SIMULATING AN EVOLUTIONARY MULTI-AGENT BASED MODEL OF THE STOCK MARKET

    Directory of Open Access Journals (Sweden)

    Diana MARICA

    2015-08-01

    Full Text Available The paper focuses on artificial stock market simulations using a multi-agent model incorporating 2,000 heterogeneous agents interacting on the artificial market. The agents interaction is due to trading activity on the market through a call auction trading mechanism. The multi-agent model uses evolutionary techniques such as genetic programming in order to generate an adaptive and evolving population of agents. Each artificial agent is endowed with wealth and a genetic programming induced trading strategy. The trading strategy evolves and adapts to the new market conditions through a process called breeding, which implies that at each simulation step, new agents with better trading strategies are generated by the model, from recombining the best performing trading strategies and replacing the agents which have the worst performing trading strategies. The simulation model was build with the help of the simulation software Altreva Adaptive Modeler which offers a suitable platform for financial market simulations of evolutionary agent based models, the S&P500 composite index being used as a benchmark for the simulation results.

  2. General Methods for Evolutionary Quantitative Genetic Inference from Generalized Mixed Models.

    Science.gov (United States)

    de Villemereuil, Pierre; Schielzeth, Holger; Nakagawa, Shinichi; Morrissey, Michael

    2016-11-01

    Methods for inference and interpretation of evolutionary quantitative genetic parameters, and for prediction of the response to selection, are best developed for traits with normal distributions. Many traits of evolutionary interest, including many life history and behavioral traits, have inherently nonnormal distributions. The generalized linear mixed model (GLMM) framework has become a widely used tool for estimating quantitative genetic parameters for nonnormal traits. However, whereas GLMMs provide inference on a statistically convenient latent scale, it is often desirable to express quantitative genetic parameters on the scale upon which traits are measured. The parameters of fitted GLMMs, despite being on a latent scale, fully determine all quantities of potential interest on the scale on which traits are expressed. We provide expressions for deriving each of such quantities, including population means, phenotypic (co)variances, variance components including additive genetic (co)variances, and parameters such as heritability. We demonstrate that fixed effects have a strong impact on those parameters and show how to deal with this by averaging or integrating over fixed effects. The expressions require integration of quantities determined by the link function, over distributions of latent values. In general cases, the required integrals must be solved numerically, but efficient methods are available and we provide an implementation in an R package, QGglmm. We show that known formulas for quantities such as heritability of traits with binomial and Poisson distributions are special cases of our expressions. Additionally, we show how fitted GLMM can be incorporated into existing methods for predicting evolutionary trajectories. We demonstrate the accuracy of the resulting method for evolutionary prediction by simulation and apply our approach to data from a wild pedigreed vertebrate population. Copyright © 2016 de Villemereuil et al.

  3. Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

    Science.gov (United States)

    Tian, Cong; Harris, Belinda S; Johnson, Kenneth R

    2016-01-01

    Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

  4. Phenotypic and evolutionary implications of modulating the ERK-MAPK cascade using the dentition as a model

    Science.gov (United States)

    Marangoni, Pauline; Charles, Cyril; Tafforeau, Paul; Laugel-Haushalter, Virginie; Joo, Adriane; Bloch-Zupan, Agnès; Klein, Ophir D.; Viriot, Laurent

    2015-06-01

    The question of phenotypic convergence across a signalling pathway has important implications for both developmental and evolutionary biology. The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2-/-, Spry4-/-, and Rsk2-/Y mice, including the incidence of extra teeth, which were lost in the mouse lineage 45 million years ago (Ma). In addition, Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning. The similarities found between teeth in fossils and mutants highlight the pivotal role of the ERK-MAPK cascade during the evolution of the dentition in rodents.

  5. Spatial multiobjective optimization of agricultural conservation practices using a SWAT model and an evolutionary algorithm.

    Science.gov (United States)

    Rabotyagov, Sergey; Campbell, Todd; Valcu, Adriana; Gassman, Philip; Jha, Manoj; Schilling, Keith; Wolter, Calvin; Kling, Catherine

    2012-12-09

    Finding the cost-efficient (i.e., lowest-cost) ways of targeting conservation practice investments for the achievement of specific water quality goals across the landscape is of primary importance in watershed management. Traditional economics methods of finding the lowest-cost solution in the watershed context (e.g.,(5,12,20)) assume that off-site impacts can be accurately described as a proportion of on-site pollution generated. Such approaches are unlikely to be representative of the actual pollution process in a watershed, where the impacts of polluting sources are often determined by complex biophysical processes. The use of modern physically-based, spatially distributed hydrologic simulation models allows for a greater degree of realism in terms of process representation but requires a development of a simulation-optimization framework where the model becomes an integral part of optimization. Evolutionary algorithms appear to be a particularly useful optimization tool, able to deal with the combinatorial nature of a watershed simulation-optimization problem and allowing the use of the full water quality model. Evolutionary algorithms treat a particular spatial allocation of conservation practices in a watershed as a candidate solution and utilize sets (populations) of candidate solutions iteratively applying stochastic operators of selection, recombination, and mutation to find improvements with respect to the optimization objectives. The optimization objectives in this case are to minimize nonpoint-source pollution in the watershed, simultaneously minimizing the cost of conservation practices. A recent and expanding set of research is attempting to use similar methods and integrates water quality models with broadly defined evolutionary optimization methods(3,4,9,10,13-15,17-19,22,23,25). In this application, we demonstrate a program which follows Rabotyagov et al.'s approach and integrates a modern and commonly used SWAT water quality model(7) with a

  6. On the validity of evolutionary models with site-specific parameters.

    Directory of Open Access Journals (Sweden)

    Konrad Scheffler

    Full Text Available Evolutionary models that make use of site-specific parameters have recently been criticized on the grounds that parameter estimates obtained under such models can be unreliable and lack theoretical guarantees of convergence. We present a simulation study providing empirical evidence that a simple version of the models in question does exhibit sensible convergence behavior and that additional taxa, despite not being independent of each other, lead to improved parameter estimates. Although it would be desirable to have theoretical guarantees of this, we argue that such guarantees would not be sufficient to justify the use of these models in practice. Instead, we emphasize the importance of taking the variance of parameter estimates into account rather than blindly trusting point estimates - this is standardly done by using the models to construct statistical hypothesis tests, which are then validated empirically via simulation studies.

  7. An evolutionary firefly algorithm for the estimation of nonlinear biological model parameters.

    Directory of Open Access Journals (Sweden)

    Afnizanfaizal Abdullah

    Full Text Available The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.

  8. An evolutionary firefly algorithm for the estimation of nonlinear biological model parameters.

    Science.gov (United States)

    Abdullah, Afnizanfaizal; Deris, Safaai; Anwar, Sohail; Arjunan, Satya N V

    2013-01-01

    The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.

  9. Differential Dynamic Evolutionary Model of Emergency Financial Service Supply Chain in Natural Disaster Risk Management

    Directory of Open Access Journals (Sweden)

    Shujian Ma

    2016-01-01

    Full Text Available A government-market-public partnership (GMPP could be a feasible arrangement for providing insurance coverage for natural disaster. Firstly, we put forward GMPP management mode. Secondly, the emergency financial service supply chain for natural disaster risk is built from the view of supply chain. Finally, the objective of this paper is to obtain insights into the cooperative and competitive relationship in GMPP system. We establish the cooperative and competitive differential dynamic evolutionary models and prove the existence of equilibrium solutions in order to solve the coordination problems. In conclusion, the equilibrium solutions can be achieved among the insurers, the operating governments, and the public.

  10. Identification of key uric acid synthesis pathway in a unique mutant silkworm Bombyx mori model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Hiroko Tabunoki

    Full Text Available Plasma uric acid (UA levels decrease following clinical progression and stage development of Parkinson's disease (PD. However, the molecular mechanisms underlying decreases in plasma UA levels remain unclear, and the potential to apply mutagenesis to a PD model has not previously been discovered. We identified a unique mutant of the silkworm Bombyx mori (B.mori op. Initially, we investigated the causality of the phenotypic "op" by microarray analysis using our constructed KAIKO functional annotation pipeline. Consequently, we found a novel UA synthesis-modulating pathway, from DJ-1 to xanthine oxidase, and established methods for large-scale analysis of gene expression in B. mori. We found that the mRNA levels of genes in this pathway were significantly lower in B. mori op mutants, indicating that downstream events in the signal transduction cascade might be prevented. Additionally, levels of B.mori tyrosine hydroxylase (TH and DJ-1 mRNA were significantly lower in the brain of B. mori op mutants. UA content was significantly lower in the B. mori op mutant tissues and hemolymph. The possibility that the B. mori op mutant might be due to loss of DJ-1 function was supported by the observed vulnerability to oxidative stress. These results suggest that UA synthesis, transport, elimination and accumulation are decreased by environmental oxidative stress in the B. mori op mutant. In the case of B. mori op mutants, the relatively low availability of UA appears to be due both to the oxidation of DJ-1 and to its expenditure to mitigate the effects of environmental oxidative stress. Our findings are expected to provide information needed to elucidate the molecular mechanism of decreased plasma UA levels in the clinical stage progression of PD.

  11. The Zebrafish Models to Explore Genetic and Epigenetic Impacts on Evolutionary Developmental Origins of Aging

    Science.gov (United States)

    Kishi, Shuji

    2014-01-01

    Can we reset, reprogram, rejuvenate or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be further manipulated into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact/noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but essentially inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena to rejuvenate over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states based on diverse epigenotypes, in response to intrinsic or extrinsic environmental cues and genetic perturbations. We hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds and windows of plasticity and its robustness by molecular genetic and chemical epigenetic approaches, we have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during their embryonic and/or larval stages (“embryonic/larval senescence”). Subsequently, at least some of these mutant animals were found to show shortened lifespan, while some others would be expected to live longer in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other

  12. Electricity demand and spot price forecasting using evolutionary computation combined with chaotic nonlinear dynamic model

    International Nuclear Information System (INIS)

    Unsihuay-Vila, C.; Zambroni de Souza, A.C.; Marangon-Lima, J.W.; Balestrassi, P.P.

    2010-01-01

    This paper proposes a new hybrid approach based on nonlinear chaotic dynamics and evolutionary strategy to forecast electricity loads and prices. The main idea is to develop a new training or identification stage in a nonlinear chaotic dynamic based predictor. In the training stage five optimal parameters for a chaotic based predictor are searched through an optimization model based on evolutionary strategy. The objective function of the optimization model is the mismatch minimization between the multi-step-ahead forecasting of predictor and observed data such as it is done in identification problems. The first contribution of this paper is that the proposed approach is capable of capturing the complex dynamic of demand and price time series considered resulting in a more accuracy forecasting. The second contribution is that the proposed approach run on-line manner, i.e. the optimal set of parameters and prediction is executed automatically which can be used to prediction in real-time, it is an advantage in comparison with other models, where the choice of their input parameters are carried out off-line, following qualitative/experience-based recipes. A case study of load and price forecasting is presented using data from New England, Alberta, and Spain. A comparison with other methods such as autoregressive integrated moving average (ARIMA) and artificial neural network (ANN) is shown. The results show that the proposed approach provides a more accurate and effective forecasting than ARIMA and ANN methods. (author)

  13. Evolutionary-Hierarchical Bases of the Formation of Cluster Model of Innovation Economic Development

    Directory of Open Access Journals (Sweden)

    Yuliya Vladimirovna Dubrovskaya

    2016-10-01

    Full Text Available The functioning of a modern economic system is based on the interaction of objects of different hierarchical levels. Thus, the problem of the study of innovation processes taking into account the mutual influence of the activities of these economic actors becomes important. The paper dwells evolutionary basis for the formation of models of innovation development on the basis of micro and macroeconomic analysis. Most of the concepts recognized that despite a big number of diverse models, the coordination of the relations between economic agents is of crucial importance for the successful innovation development. According to the results of the evolutionary-hierarchical analysis, the authors reveal key phases of the development of forms of business cooperation, science and government in the domestic economy. It has become the starting point of the conception of the characteristics of the interaction in the cluster models of innovation development of the economy. Considerable expectancies on improvement of the national innovative system are connected with the development of cluster and network structures. The main objective of government authorities is the formation of mechanisms and institutions that will foster cooperation between members of the clusters. The article explains that the clusters cannot become the factors in the growth of the national economy, not being an effective tool for interaction between the actors of the regional innovative systems.

  14. AFM images of complexes between amylose and Aspergillus niger glucoamylase mutants, native and mutant starch binding domains: a model for the action of glucoamylase

    DEFF Research Database (Denmark)

    Morris, V. M.; Gunning, A. P.; Faults, C. B.

    2005-01-01

    Atomic force microscopy has been used to investigate the complexes formed between high molecular weight amylose chains and Aspergillus niger glucoamylase mutants (E400Q and W52F), wild-type A. niger starch binding domains (SBDS), and mutant SBDs (W563K and W590K) lacking either of the two starch...

  15. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  16. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

    NARCIS (Netherlands)

    Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.

    Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35:

  17. MESA models of the evolutionary state of the interacting binary epsilon Aurigae

    Science.gov (United States)

    Gibson, Justus L.; Stencel, Robert E.

    2018-06-01

    Using MESA code (Modules for Experiments in Stellar Astrophysics, version 9575), an evaluation was made of the evolutionary state of the epsilon Aurigae binary system (HD 31964, F0Iap + disc). We sought to satisfy several observational constraints: (1) requiring evolutionary tracks to pass close to the current temperature and luminosity of the primary star; (2) obtaining a period near the observed value of 27.1 years; (3) matching a mass function of 3.0; (4) concurrent Roche lobe overflow and mass transfer; (5) an isotopic ratio 12C/13C = 5 and, (6) matching the interferometrically determined angular diameter. A MESA model starting with binary masses of 9.85 + 4.5 M⊙, with a 100 d initial period, produces a 1.2 + 10.6 M⊙ result having a 547 d period, and a single digit 12C/13C ratio. These values were reached near an age of 20 Myr, when the donor star comes close to the observed luminosity and temperature for epsilon Aurigae A, as a post-RGB/pre-AGB star. Contemporaneously, the accretor then appears as an upper main-sequence, early B-type star. This benchmark model can provide a basis for further exploration of this interacting binary, and other long-period binary stars.

  18. Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

    Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

  19. When It’s Good to Feel Bad: An Evolutionary Model of Guilt and Apology

    Directory of Open Access Journals (Sweden)

    Sarita Rosenstock

    2018-03-01

    Full Text Available We use techniques from evolutionary game theory to analyze the conditions under which guilt can provide individual fitness benefits, and so evolve. In particular, we focus on the benefits of guilty apology. We consider models where actors err in an iterated prisoner’s dilemma and have the option to apologize. Guilt either improves the trustworthiness of apology or imposes a cost on actors who apologize. We analyze the stability and likelihood of evolution of such a “guilt-prone” strategy against cooperators, defectors, grim triggers, and individuals who offer fake apologies, but continue to defect. We find that in evolutionary models guilty apology is more likely to evolve in cases where actors interact repeatedly over long periods of time, where the costs of apology are low or moderate, and where guilt is hard to fake. Researchers interested in naturalized ethics, and emotion researchers, can employ these results to assess the plausibility of fuller accounts of the evolution of guilt.

  20. Risk attitudes in a changing environment: An evolutionary model of the fourfold pattern of risk preferences.

    Science.gov (United States)

    Mallpress, Dave E W; Fawcett, Tim W; Houston, Alasdair I; McNamara, John M

    2015-04-01

    A striking feature of human decision making is the fourfold pattern of risk attitudes, involving risk-averse behavior in situations of unlikely losses and likely gains, but risk-seeking behavior in response to likely losses and unlikely gains. Current theories to explain this pattern assume particular psychological processes to reproduce empirical observations, but do not address whether it is adaptive for the decision maker to respond to risk in this way. Here, drawing on insights from behavioral ecology, we build an evolutionary model of risk-sensitive behavior, to investigate whether particular types of environmental conditions could favor a fourfold pattern of risk attitudes. We consider an individual foraging in a changing environment, where energy is needed to prevent starvation and build up reserves for reproduction. The outcome, in terms of reproductive value (a rigorous measure of evolutionary success), of a one-off choice between a risky and a safe gain, or between a risky and a safe loss, determines the risk-sensitive behavior we should expect to see in this environment. Our results show that the fourfold pattern of risk attitudes may be adaptive in an environment in which conditions vary stochastically but are autocorrelated in time. In such an environment the current options provide information about the likely environmental conditions in the future, which affect the optimal pattern of risk sensitivity. Our model predicts that risk preferences should be both path dependent and affected by the decision maker's current state. (c) 2015 APA, all rights reserved).

  1. Adaptive evolutionary walks require neutral intermediates in RNA fitness landscapes.

    Science.gov (United States)

    Rendel, Mark D

    2011-01-01

    In RNA fitness landscapes with interconnected networks of neutral mutations, neutral precursor mutations can play an important role in facilitating the accessibility of epistatic adaptive mutant combinations. I use an exhaustively surveyed fitness landscape model based on short sequence RNA genotypes (and their secondary structure phenotypes) to calculate the minimum rate at which mutants initially appearing as neutral are incorporated into an adaptive evolutionary walk. I show first, that incorporating neutral mutations significantly increases the number of point mutations in a given evolutionary walk when compared to estimates from previous adaptive walk models. Second, that incorporating neutral mutants into such a walk significantly increases the final fitness encountered on that walk - indeed evolutionary walks including neutral steps often reach the global optimum in this model. Third, and perhaps most importantly, evolutionary paths of this kind are often extremely winding in their nature and have the potential to undergo multiple mutations at a given sequence position within a single walk; the potential of these winding paths to mislead phylogenetic reconstruction is briefly considered. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. The causal pie model: an epidemiological method applied to evolutionary biology and ecology.

    Science.gov (United States)

    Wensink, Maarten; Westendorp, Rudi G J; Baudisch, Annette

    2014-05-01

    A general concept for thinking about causality facilitates swift comprehension of results, and the vocabulary that belongs to the concept is instrumental in cross-disciplinary communication. The causal pie model has fulfilled this role in epidemiology and could be of similar value in evolutionary biology and ecology. In the causal pie model, outcomes result from sufficient causes. Each sufficient cause is made up of a "causal pie" of "component causes". Several different causal pies may exist for the same outcome. If and only if all component causes of a sufficient cause are present, that is, a causal pie is complete, does the outcome occur. The effect of a component cause hence depends on the presence of the other component causes that constitute some causal pie. Because all component causes are equally and fully causative for the outcome, the sum of causes for some outcome exceeds 100%. The causal pie model provides a way of thinking that maps into a number of recurrent themes in evolutionary biology and ecology: It charts when component causes have an effect and are subject to natural selection, and how component causes affect selection on other component causes; which partitions of outcomes with respect to causes are feasible and useful; and how to view the composition of a(n apparently homogeneous) population. The diversity of specific results that is directly understood from the causal pie model is a test for both the validity and the applicability of the model. The causal pie model provides a common language in which results across disciplines can be communicated and serves as a template along which future causal analyses can be made.

  3. Energy demand forecasting in Iranian metal industry using linear and nonlinear models based on evolutionary algorithms

    International Nuclear Information System (INIS)

    Piltan, Mehdi; Shiri, Hiva; Ghaderi, S.F.

    2012-01-01

    Highlights: ► Investigating different fitness functions for evolutionary algorithms in energy forecasting. ► Energy forecasting of Iranian metal industry by value added, energy prices, investment and employees. ► Using real-coded instead of binary-coded genetic algorithm decreases energy forecasting error. - Abstract: Developing energy-forecasting models is known as one of the most important steps in long-term planning. In order to achieve sustainable energy supply toward economic development and social welfare, it is required to apply precise forecasting model. Applying artificial intelligent models for estimation complex economic and social functions is growing up considerably in many researches recently. In this paper, energy consumption in industrial sector as one of the critical sectors in the consumption of energy has been investigated. Two linear and three nonlinear functions have been used in order to forecast and analyze energy in the Iranian metal industry, Particle Swarm Optimization (PSO) and Genetic Algorithms (GAs) are applied to attain parameters of the models. The Real-Coded Genetic Algorithm (RCGA) has been developed based on real numbers, which is introduced as a new approach in the field of energy forecasting. In the proposed model, electricity consumption has been considered as a function of different variables such as electricity tariff, manufacturing value added, prevailing fuel prices, the number of employees, the investment in equipment and consumption in the previous years. Mean Square Error (MSE), Root Mean Square Error (RMSE), Mean Absolute Deviation (MAD) and Mean Absolute Percent Error (MAPE) are the four functions which have been used as the fitness function in the evolutionary algorithms. The results show that the logarithmic nonlinear model using PSO algorithm with 1.91 error percentage has the best answer. Furthermore, the prediction of electricity consumption in industrial sector of Turkey and also Turkish industrial sector

  4. Design and selection of load control strategies using a multiple objective model and evolutionary algorithms

    International Nuclear Information System (INIS)

    Gomes, Alvaro; Antunes, Carlos Henggeler; Martins, Antonio Gomes

    2005-01-01

    This paper aims at presenting a multiple objective model to evaluate the attractiveness of the use of demand resources (through load management control actions) by different stakeholders and in diverse structure scenarios in electricity systems. For the sake of model flexibility, the multiple (and conflicting) objective functions of technical, economical and quality of service nature are able to capture distinct market scenarios and operating entities that may be interested in promoting load management activities. The computation of compromise solutions is made by resorting to evolutionary algorithms, which are well suited to tackle multiobjective problems of combinatorial nature herein involving the identification and selection of control actions to be applied to groups of loads. (Author)

  5. The evolutionary reserve cell concept and model of cellular response induced by low doses of radiation

    International Nuclear Information System (INIS)

    Spitkovsky, D.M.; Talyzina, T.A.

    1995-01-01

    The model is based on the concept of programmed initiation of genetic damage in sub-populations of specific evolutionary reserve cells (ERC). The model quantitatively predicts a dose response of genetic lesions at low dose range and furnishes an explanation of the minimum observed in the dose-response curve at doses corresponding to one (on the average) event of energy deposition per ERC. The complex shape of the dose-response curve is demonstrated to result from superposition of processes in different sub-populations within the exposed cell population (at low doses mainly in ERC). Programmed initiation of genetic lesions in ERC requires two hits to cell membrane and probably, at the same time, to the cell nucleus. The equation for dicentric yield in human lymphocytes as a function of dose describes the experimental observations rather well. (Author)

  6. The deep subterranean environment as a potential model system in ecological, biogeographical and evolutionary research

    Directory of Open Access Journals (Sweden)

    David Sánchez-Fernández

    2018-01-01

    Full Text Available One of the main challenges in ecology, biogeography and evolution is to understand and predict how species may respond to environmental changes. Here we focus on the deep subterranean environment, a system that minimizes most of the typical uncertainties of studies on epigean (surface environments. Caves are relatively homogeneous habitats with nearly constant environmental conditions and simplified biological communities, allowing to control for biotic interactions. Thus, this particular system could be considered a natural habitat whose environmental conditions are similar to what can be reproduced in a laboratory, being an ideal model system for ecological, biogeographical and evolutionary studies. Subterranean species may potentially be used to assess the capability to persist in situ in a global change scenario, as they cannot accommodate to drastic changing conditions by behavioural plasticity, microhabitat use or by migrating to distant, more suitable areas, something frequent in epigean environments. In order to provide accurate predictions of the response of the subterranean biodiversity to climate change, we encourage evolutionary biologist, biogeographers and conservation biologist to work in this interesting ecosystem.

  7. Evolutionary responses to a constructed niche: ancient Mesoamericans as a model of gene-culture coevolution.

    Directory of Open Access Journals (Sweden)

    Tábita Hünemeier

    Full Text Available Culture and genetics rely on two distinct but not isolated transmission systems. Cultural processes may change the human selective environment and thereby affect which individuals survive and reproduce. Here, we evaluated whether the modes of subsistence in Native American populations and the frequencies of the ABCA1*Arg230Cys polymorphism were correlated. Further, we examined whether the evolutionary consequences of the agriculturally constructed niche in Mesoamerica could be considered as a gene-culture coevolution model. For this purpose, we genotyped 229 individuals affiliated with 19 Native American populations and added data for 41 other Native American groups (n = 1905 to the analysis. In combination with the SNP cluster of a neutral region, this dataset was then used to unravel the scenario involved in 230Cys evolutionary history. The estimated age of 230Cys is compatible with its origin occurring in the American continent. The correlation of its frequencies with the archeological data on Zea pollen in Mesoamerica/Central America, the neutral coalescent simulations, and the F(ST-based natural selection analysis suggest that maize domestication was the driving force in the increase in the frequencies of 230Cys in this region. These results may represent the first example of a gene-culture coevolution involving an autochthonous American allele.

  8. Evolutionary molecular medicine.

    Science.gov (United States)

    Nesse, Randolph M; Ganten, Detlev; Gregory, T Ryan; Omenn, Gilbert S

    2012-05-01

    Evolution has long provided a foundation for population genetics, but some major advances in evolutionary biology from the twentieth century that provide foundations for evolutionary medicine are only now being applied in molecular medicine. They include the need for both proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, competition between alleles, co-evolution, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are transforming evolutionary biology in ways that create even more opportunities for progress at its interfaces with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine.

  9. Structure-based Markov random field model for representing evolutionary constraints on functional sites.

    Science.gov (United States)

    Jeong, Chan-Seok; Kim, Dongsup

    2016-02-24

    Elucidating the cooperative mechanism of interconnected residues is an important component toward understanding the biological function of a protein. Coevolution analysis has been developed to model the coevolutionary information reflecting structural and functional constraints. Recently, several methods have been developed based on a probabilistic graphical model called the Markov random field (MRF), which have led to significant improvements for coevolution analysis; however, thus far, the performance of these models has mainly been assessed by focusing on the aspect of protein structure. In this study, we built an MRF model whose graphical topology is determined by the residue proximity in the protein structure, and derived a novel positional coevolution estimate utilizing the node weight of the MRF model. This structure-based MRF method was evaluated for three data sets, each of which annotates catalytic site, allosteric site, and comprehensively determined functional site information. We demonstrate that the structure-based MRF architecture can encode the evolutionary information associated with biological function. Furthermore, we show that the node weight can more accurately represent positional coevolution information compared to the edge weight. Lastly, we demonstrate that the structure-based MRF model can be reliably built with only a few aligned sequences in linear time. The results show that adoption of a structure-based architecture could be an acceptable approximation for coevolution modeling with efficient computation complexity.

  10. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Directory of Open Access Journals (Sweden)

    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  11. Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health.

    Science.gov (United States)

    Raichlen, David A; Alexander, Gene E

    2017-07-01

    The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging? Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Generation of comprehensive transposon insertion mutant library for the model archaeon, Haloferax volcanii, and its use for gene discovery.

    Science.gov (United States)

    Kiljunen, Saija; Pajunen, Maria I; Dilks, Kieran; Storf, Stefanie; Pohlschroder, Mechthild; Savilahti, Harri

    2014-12-09

    Archaea share fundamental properties with bacteria and eukaryotes. Yet, they also possess unique attributes, which largely remain poorly characterized. Haloferax volcanii is an aerobic, moderately halophilic archaeon that can be grown in defined media. It serves as an excellent archaeal model organism to study the molecular mechanisms of biological processes and cellular responses to changes in the environment. Studies on haloarchaea have been impeded by the lack of efficient genetic screens that would facilitate the identification of protein functions and respective metabolic pathways. Here, we devised an insertion mutagenesis strategy that combined Mu in vitro DNA transposition and homologous-recombination-based gene targeting in H. volcanii. We generated an insertion mutant library, in which the clones contained a single genomic insertion. From the library, we isolated pigmentation-defective and auxotrophic mutants, and the respective insertions pinpointed a number of genes previously known to be involved in carotenoid and amino acid biosynthesis pathways, thus validating the performance of the methodologies used. We also identified mutants that had a transposon insertion in a gene encoding a protein of unknown or putative function, demonstrating that novel roles for non-annotated genes could be assigned. We have generated, for the first time, a random genomic insertion mutant library for a halophilic archaeon and used it for efficient gene discovery. The library will facilitate the identification of non-essential genes behind any specific biochemical pathway. It represents a significant step towards achieving a more complete understanding of the unique characteristics of halophilic archaea.

  13. Radio-sensitivity of the cells from amyotrophic lateral sclerosis model mice transfected with human mutant SOD1

    International Nuclear Information System (INIS)

    Wate, Reika; Ito, Hidefumi; Kusaka, Hirofumi; Takahashi, Sentaro; Kubota, Yoshihisa; Suetomi, Katsutoshi; Sato, Hiroshi; Okayasu, Ryuichi

    2005-01-01

    In order to clarify the possible involvement of oxidative damage induced by ionizing radiation in the onset and/or progression of familial amyotrophic lateral sclerosis (ALS), we studied radio-sensitivity in primary cells derived from ALS model mice expressing human mutant Cu/Zn superoxide dismutase (SOD1). The primary mouse cells expressed both mouse and the mutant human SOD1. The cell survival of the transgenic mice (with mutant SOD1), determined by counting cell numbers at a scheduled time after X-irradiation, is very similar to that of cells from wild type animals. The induction and repair of DNA damage in the transgenic cells, measured by single cell gel electrophoresis and pulsed field gel electrophoresis, are also similar to those of wild type cells. These results indicate that the human mutant SOD1 gene does not seem to contribute to the alteration of radio-sensitivity, at least in the fibroblastic cells used here. Although it is necessary to consider the difference in cell types between fibroblastic and neuronal cells, the present results may suggest that ionizing radiation is not primarily responsible for the onset of familial ALS with the SOD1 mutation, and that the excess risks are probably not a concern for radiation diagnosis and therapy in familial ALS patients. (author)

  14. MESA models for the evolutionary status of the epsilon Aurigae disk-eclipsed binary system

    Science.gov (United States)

    Stencel, Robert E.; Gibson, Justus

    2018-06-01

    The brightest member of the class of disk-eclipsed binary stars is the Algol-like long-period binary, epsilon Aurigae (HD 31964, F0Iap + disk, http://adsabs.harvard.edu/abs/2016SPIE.9907E..17S ). Using MESA (Modules for Experiments in Stellar Astrophysics, version 9575), we have made an evaluation of its evolutionary state. We sought to satisfy several observational constraints, including: (1) requiring evolutionary tracks to pass close to the current temperature and luminosity of the primary star; (2) obtaining a period near the observed value of 27.1 years; (3) matching a mass function of 3.0; (4) concurrent Roche lobe overflow and mass transfer; (5) an isotopic ratio 12C / 13C = 5 and, (6) matching the interferometrically determined angular diameter. A MESA model starting with binary masses of 9.85 + 4.5 solar masses, with a 100 day initial period, produces a 1.2 + 10.6 solar masses result having a 547 day period, plus a single digit 12C / 13C ratio. These values were reached near an age of 20 Myr, when the donor star comes close to the observed luminosity and temperature for epsilon Aurigae A, as a post-RGB/pre-AGB star. Contemporaneously, the accretor then appears as an upper main sequence, early B-type star. This benchmark model can provide a basis for further exploration of this interacting binary, and other long period binary stars. This report has been submitted to MNRAS, along with a parallel investigation of mass transfer stream and disk sub-structure. The authors are grateful to the estate of William Herschel Womble for the support of astronomy at the University of Denver.

  15. Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism.

    Science.gov (United States)

    Ju, Anes; Hammerschmidt, Kurt; Tantra, Martesa; Krueger, Dilja; Brose, Nils; Ehrenreich, Hannelore

    2014-08-15

    Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Loss-of-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(-/-) mice have not been reported yet. The present study has been designed to systematically investigate in male and female Nlgn4(-/-) pups versus wildtype littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in Nlgn4(-/-) mice that appear more pronounced in immature females with their overall stronger USV as compared to males. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.

    Science.gov (United States)

    Ihara, Tatsuya; Mitsui, Takahiko; Nakamura, Yuki; Kira, Satoru; Miyamoto, Tatsuya; Nakagomi, Hiroshi; Sawada, Norifumi; Hirayama, Yuri; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Yoichi; Yoshiyama, Mitsuharu; Andersson, Karl-Erik; Nakao, Atsuhito; Takeda, Masayuki; Koizumi, Schuichi

    2017-04-01

    The pathophysiologies of nocturia (NOC) and nocturnal polyuria (NP) are multifactorial and their etiologies remain unclear in a large number of patients. Clock genes exist in most cells and organs, and the products of Clock regulate circadian rhythms as representative clock genes. Clock genes regulate lower urinary tract function, and a newly suggested concept is that abnormalities in clock genes cause lower urinary tract symptoms. In the present study, we investigated the voiding behavior of Clock mutant (Clock Δ19/Δ19 ) mice in order to determine the effects of clock genes on NOC/NP. Male C57BL/6 mice aged 8-12 weeks (WT) and male C57BL/6 Clock Δ19/Δ19 mice aged 8 weeks were used. They were bred under 12 hr light/dark conditions for 2 weeks and voiding behavior was investigated by measuring water intake volume, urine volume, urine volume/void, and voiding frequency in metabolic cages in the dark and light periods. No significant differences were observed in behavior patterns between Clock Δ19/Δ19 and WT mice. Clock Δ19/Δ19 mice showed greater voiding frequencies and urine volumes during the sleep phase than WT mice. The diurnal change in urine volume/void between the dark and light periods in WT mice was absent in Clock Δ19/Δ19 mice. Additionally, functional bladder capacity was significantly lower in Clock Δ19/Δ19 mice than in WT mice. We demonstrated that Clock Δ19/Δ19 mice showed the phenotype of NOC/NP. The Clock Δ19/Δ19 mouse may be used as an animal model of NOC and NP. Neurourol. Urodynam. 36:1034-1038, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Probing evolutionary population synthesis models in the near infrared with early-type galaxies

    Science.gov (United States)

    Dahmer-Hahn, Luis Gabriel; Riffel, Rogério; Rodríguez-Ardila, Alberto; Martins, Lucimara P.; Kehrig, Carolina; Heckman, Timothy M.; Pastoriza, Miriani G.; Dametto, Natacha Z.

    2018-06-01

    We performed a near-infrared (NIR; ˜1.0 -2.4 μm) stellar population study in a sample of early-type galaxies. The synthesis was performed using five different evolutionary population synthesis libraries of models. Our main results can be summarized as follows: low-spectral-resolution libraries are not able to produce reliable results when applied to the NIR alone, with each library finding a different dominant population. The two newest higher resolution models, on the other hand, perform considerably better, finding consistent results to each other and to literature values. We also found that optical results are consistent with each other even for lower resolution models. We also compared optical and NIR results and found out that lower resolution models tend to disagree in the optical and in the NIR, with higher fraction of young populations in the NIR and dust extinction ˜1 mag higher than optical values. For higher resolution models, optical and NIR results tend to agree much better, suggesting that a higher spectral resolution is fundamental to improve the quality of the results.

  18. Combining Interactive Infrastructure Modeling and Evolutionary Algorithm Optimization for Sustainable Water Resources Design

    Science.gov (United States)

    Smith, R.; Kasprzyk, J. R.; Zagona, E. A.

    2013-12-01

    Population growth and climate change, combined with difficulties in building new infrastructure, motivate portfolio-based solutions to ensuring sufficient water supply. Powerful simulation models with graphical user interfaces (GUI) are often used to evaluate infrastructure portfolios; these GUI based models require manual modification of the system parameters, such as reservoir operation rules, water transfer schemes, or system capacities. Multiobjective evolutionary algorithm (MOEA) based optimization can be employed to balance multiple objectives and automatically suggest designs for infrastructure systems, but MOEA based decision support typically uses a fixed problem formulation (i.e., a single set of objectives, decisions, and constraints). This presentation suggests a dynamic framework for linking GUI-based infrastructure models with MOEA search. The framework begins with an initial formulation which is solved using a MOEA. Then, stakeholders can interact with candidate solutions, viewing their properties in the GUI model. This is followed by changes in the formulation which represent users' evolving understanding of exigent system properties. Our case study is built using RiverWare, an object-oriented, data-centered model that facilitates the representation of a diverse array of water resources systems. Results suggest that assumptions within the initial MOEA search are violated after investigating tradeoffs and reveal how formulations should be modified to better capture stakeholders' preferences.

  19. An integrative model of evolutionary covariance: a symposium on body shape in fishes.

    Science.gov (United States)

    Walker, Jeffrey A

    2010-12-01

    A major direction of current and future biological research is to understand how multiple, interacting functional systems coordinate in producing a body that works. This understanding is complicated by the fact that organisms need to work well in multiple environments, with both predictable and unpredictable environmental perturbations. Furthermore, organismal design reflects a history of past environments and not a plan for future environments. How complex, interacting functional systems evolve, then, is a truly grand challenge. In accepting the challenge, an integrative model of evolutionary covariance is developed. The model combines quantitative genetics, functional morphology/physiology, and functional ecology. The model is used to convene scientists ranging from geneticists, to physiologists, to ecologists, to engineers to facilitate the emergence of body shape in fishes as a model system for understanding how complex, interacting functional systems develop and evolve. Body shape of fish is a complex morphology that (1) results from many developmental paths and (2) functions in many different behaviors. Understanding the coordination and evolution of the many paths from genes to body shape, body shape to function, and function to a working fish body in a dynamic environment is now possible given new technologies from genetics to engineering and new theoretical models that integrate the different levels of biological organization (from genes to ecology).

  20. Some Analytical Properties of the Model for Stochastic Evolutionary Games in Finite Populations with Non-uniform Interaction Rate

    International Nuclear Information System (INIS)

    Quan Ji; Wang Xianjia

    2013-01-01

    Traditional evolutionary games assume uniform interaction rate, which means that the rate at which individuals meet and interact is independent of their strategies. But in some systems, especially biological systems, the players interact with each other discriminately. Taylor and Nowak (2006) were the first to establish the corresponding non-uniform interaction rate model by allowing the interaction rates to depend on strategies. Their model is based on replicator dynamics which assumes an infinite size population. But in reality, the number of individuals in the population is always finite, and there will be some random interference in the individuals' strategy selection process. Therefore, it is more practical to establish the corresponding stochastic evolutionary model in finite populations. In fact, the analysis of evolutionary games in a finite size population is more difficult. Just as Taylor and Nowak said in the outlook section of their paper, ''The analysis of non-uniform interaction rates should be extended to stochastic game dynamics of finite populations''. In this paper, we are exactly doing this work. We extend Taylor and Nowak's model from infinite to finite case, especially focusing on the infiuence of non-uniform connection characteristics on the evolutionary stable state of the system. We model the strategy evolutionary process of the population by a continuous ergodic Markov process. Based on the limit distribution of the process, we can give the evolutionary stable state of the system. We make a complete classification of the symmetric 2 × 2 games. For each case game, the corresponding limit distribution of the Markov-based process is given when noise intensity is small enough. In contrast with most literatures in evolutionary games using the simulation method, all our results obtained are analytical. Especially, in the dominant-case game, coexistence of the two strategies may become evolutionary stable states in our model. This result can be

  1. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

    NARCIS (Netherlands)

    Simeonova, I.; Jaber, S.; Draskovic, I.; Bardot, B.; Fang, M.; Bouarich-Bourimi, R.; Lejour, V.; Charbonnier, L.; Soudais, C.; Bourdon, J.C.; Huerre, M.; Londono-Vallejo, A.; Toledo, F.

    2013-01-01

    Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53(Delta31), a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis,

  2. Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy.

    Science.gov (United States)

    Freidl, Raphaela; Gstoettner, Antonia; Baranyi, Ulrike; Swoboda, Ines; Stolz, Frank; Focke-Tejkl, Margarete; Wekerle, Thomas; van Ree, Ronald; Valenta, Rudolf; Linhart, Birgit

    2017-06-01

    Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed. This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunization with a hypoallergenic mutant of the major carp allergen protect against allergic symptoms in sensitized mice. C3H/HeJ mice were sensitized with recombinant wildtype Cyp c 1 or carp extract by intragastric gavage. Antibody, cellular immune responses, and epitope specificity in sensitized mice were investigated by ELISA, rat basophil leukemia assay, T-cell proliferation experiments using recombinant wildtype Cyp c 1, and overlapping peptides spanning the Cyp c 1 sequence. Anti-hypoallergenic Cyp c 1 mutant mouse and rabbit sera were tested for their ability to inhibit IgE recognition of Cyp c 1, Cyp c 1-specific basophil degranulation, and Cyp c 1-induced allergic symptoms in the mouse model. A mouse model of fish allergy mimicking human disease regarding IgE epitope recognition and symptoms as close as possible was established. Administration of antisera generated in mice and rabbits by immunization with a hypoallergenic Cyp c 1 mutant inhibited IgE binding to Cyp c 1, Cyp c 1-induced basophil degranulation, and allergic symptoms caused by allergen challenge in sensitized mice. Antibodies induced by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic reactions in a murine model of fish allergy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Direct Test of the Brown Dwarf Evolutionary Models Through Secondary Eclipse Spectroscopy of LHS 6343

    Science.gov (United States)

    Albert, Loic

    2015-10-01

    As the number of field Brown Dwarfs counts in the thousands, interpreting their physical parameters (mass, temperature, radius, luminosity, age, metallicity) relies as heavily as ever on atmosphere and evolutionary models. Fortunately, models are largely successful in explaining observations (colors, spectral types, luminosity), so they appear well calibrated in a relative sense. However, an absolute model-independent calibration is still lacking. Eclipsing BDs systems are a unique laboratory in this respect but until recently only one such system was known, 2M0535-05 - a very young (1 Gyr) - was identified (62.1+/-1.2 MJup, 0.783+/-0.011 RJup) transiting LHS6343 with a 12.7-day period. We propose to use WFC3 in drift scan mode and 5 HST orbits to determine the spectral type (a proxy for temperature) as well as the near-infrared luminosity of this brown dwarf. We conducted simulations that predict a signal-to-noise ratio ranging between 10 and 30 per resolution element in the peaks of the spectrum. These measurements, coupled with existing luminosity measurements with Spitzer at 3.6 and 4.5 microns, will allow us to trace the spectral energy distribution of the Brown Dwarf and directly calculate its blackbody temperature. It will be the first field Brown Dwarfs with simultaneous measurements of its radius, mass, luminosity and temperature all measured independently of models.

  4. An Evolutionary Algorithm for Multiobjective Fuzzy Portfolio Selection Models with Transaction Cost and Liquidity

    Directory of Open Access Journals (Sweden)

    Wei Yue

    2015-01-01

    Full Text Available The major issues for mean-variance-skewness models are the errors in estimations that cause corner solutions and low diversity in the portfolio. In this paper, a multiobjective fuzzy portfolio selection model with transaction cost and liquidity is proposed to maintain the diversity of portfolio. In addition, we have designed a multiobjective evolutionary algorithm based on decomposition of the objective space to maintain the diversity of obtained solutions. The algorithm is used to obtain a set of Pareto-optimal portfolios with good diversity and convergence. To demonstrate the effectiveness of the proposed model and algorithm, the performance of the proposed algorithm is compared with the classic MOEA/D and NSGA-II through some numerical examples based on the data of the Shanghai Stock Exchange Market. Simulation results show that our proposed algorithm is able to obtain better diversity and more evenly distributed Pareto front than the other two algorithms and the proposed model can maintain quite well the diversity of portfolio. The purpose of this paper is to deal with portfolio problems in the weighted possibilistic mean-variance-skewness (MVS and possibilistic mean-variance-skewness-entropy (MVS-E frameworks with transaction cost and liquidity and to provide different Pareto-optimal investment strategies as diversified as possible for investors at a time, rather than one strategy for investors at a time.

  5. BIRDS AS A MODEL TO STUDY ADULT NEUROGENESIS: BRIDGING EVOLUTIONARY, COMPARATIVE AND NEUROETHOLOGICAL APPROCHES

    Science.gov (United States)

    BARNEA, ANAT; PRAVOSUDOV, VLADIMIR

    2011-01-01

    During the last few decades evidence has demonstrated that adult neurogenesis is a well-preserved feature throughout the animal kingdom. In birds, ongoing neuronal addition occurs rather broadly, to a number of brain regions. This review describes adult avian neurogenesis and neuronal recruitment, discusses factors that regulate these processes, and touches upon the question of their genetic control. Several attributes make birds an extremely advantageous model to study neurogenesis. First, song learning exhibits seasonal variation that is associated with seasonal variation in neuronal turnover in some song control brain nuclei, which seems to be regulated via adult neurogenesis. Second, food-caching birds naturally use memory-dependent behavior in learning locations of thousands of food caches scattered over their home ranges. In comparison with other birds, food-caching species have relatively enlarged hippocampi with more neurons and intense neurogenesis, which appears to be related to spatial learning. Finally, migratory behavior and naturally occurring social systems in birds also provide opportunities to investigate neurogenesis. Such diversity of naturally-occurring memory-based behaviors, combined with the fact that birds can be studied both in the wild and in the laboratory, make them ideal for investigation of neural processes underlying learning. This can be done by using various approaches, from evolutionary and comparative to neuroethological and molecular. Finally, we connect the avian arena to a broader view by providing a brief comparative and evolutionary overview of adult neurogenesis and by discussing the possible functional role of the new neurons. We conclude by indicating future directions and possible medical applications. PMID:21929623

  6. Grand challenges in evolutionary and population genetics: The importance of integrating epigenetics, genomics, modeling, and experimentation

    Science.gov (United States)

    Samuel A. Cushman

    2014-01-01

    This is a time of explosive growth in the fields of evolutionary and population genetics, with whole genome sequencing and bioinformatics driving a transformative paradigm shift (Morozova and Marra, 2008). At the same time, advances in epigenetics are thoroughly transforming our understanding of evolutionary processes and their implications for populations, species and...

  7. An affinity-based evolutionary model of the diffusion of knowledge

    Directory of Open Access Journals (Sweden)

    Roberto Luiz Souza Monteiro

    2015-08-01

    Full Text Available In this paper, we present a theoretical model that can simulate the diffusion of knowledge in social networks using an evolutionary approach. We assume that social networks built on processes of collaboration and cooperation among stakeholders (people and companies evolve like living organisms, as described by Charles Darwin in The Origin of Species. We propose an evolutionary model of the diffusion of knowledge, in which stakeholders are knowledge propagators and/or receivers, depending on their customizable attributes. We consider each attribute as a gene that constitutes a chromosome. As in Darwin's theory, the proposed model achieves the processes of crossover and mutation between stakeholders for several generations, until a maximum number of generations is reached. The main contribution of the model is the creation of an environment that is conducive to the study of the dynamics of network cooperation, which uses the stakeholders’ attributes as parameters. Modelo evolutivo de difusión del conocimiento basado en afinidad Resumen En este artículo presentamos un modelo teórico capaz de simular la difusión del conocimiento en redes sociales, usando una aproximación evolutiva. Partimos del presupuesto que redes sociales constituidas por procesos de cooperación entre actores (e.g. personas, empresas, etc. evolucionan de forma semejante a los organismos vivos, como ha sido descrito por Charles Darwin en El Origen de las Especies. Proponemos un modelo evolutivo de difusión del conocimiento, donde los actores son propagadores y/o retenedores de conocimiento, dependiendo de atributos ajustables que cada actor presenta. Consideramos cada atributo un gen que constituye a un cromosoma. Similar a la teoría de Darwin, el modelo propuesto realiza los procesos de crossover y mutación entre los actores por diversas generaciones, hasta que se obtiene un número máximo de generaciones. La principal contribución del modelo es la creación de un

  8. A molecular phylogeny of nephilid spiders: evolutionary history of a model lineage.

    Science.gov (United States)

    Kuntner, Matjaž; Arnedo, Miquel A; Trontelj, Peter; Lokovšek, Tjaša; Agnarsson, Ingi

    2013-12-01

    The pantropical orb web spider family Nephilidae is known for the most extreme sexual size dimorphism among terrestrial animals. Numerous studies have made Nephilidae, particularly Nephila, a model lineage in evolutionary research. However, a poorly understood phylogeny of this lineage, relying only on morphology, has prevented thorough evolutionary syntheses of nephilid biology. We here use three nuclear and five mitochondrial genes for 28 out of 40 nephilid species to provide a more robust nephilid phylogeny and infer clade ages in a fossil-calibrated Bayesian framework. We complement the molecular analyses with total evidence analysis including morphology. All analyses find strong support for nephilid monophyly and exclusivity and the monophyly of the genera Herennia and Clitaetra. The inferred phylogenetic structure within Nephilidae is novel and conflicts with morphological phylogeny and traditional taxonomy. Nephilengys species fall into two clades, one with Australasian species (true Nephilengys) as sister to Herennia, and another with Afrotropical species (Nephilingis Kuntner new genus) as sister to a clade containing Clitaetra plus most currently described Nephila. Surprisingly, Nephila is also diphyletic, with true Nephila containing N. pilipes+N. constricta, and the second clade with all other species sister to Clitaetra; this "Nephila" clade is further split into an Australasian clade that also contains the South American N. sexpunctata and the Eurasian N. clavata, and an African clade that also contains the Panamerican N. clavipes. An approximately unbiased test constraining the monophyly of Nephilengys, Nephila, and Nephilinae (Nephila, Nephilengys, Herennia), respectively, rejected Nephilengys monophyly, but not that of Nephila and Nephilinae. Further data are therefore necessary to robustly test these two new, but inconclusive findings, and also to further test the precise placement of Nephilidae within the Araneoidea. For divergence date estimation

  9. A sense of life: computational and experimental investigations with models of biochemical and evolutionary processes.

    Science.gov (United States)

    Mishra, Bud; Daruwala, Raoul-Sam; Zhou, Yi; Ugel, Nadia; Policriti, Alberto; Antoniotti, Marco; Paxia, Salvatore; Rejali, Marc; Rudra, Archisman; Cherepinsky, Vera; Silver, Naomi; Casey, William; Piazza, Carla; Simeoni, Marta; Barbano, Paolo; Spivak, Marina; Feng, Jiawu; Gill, Ofer; Venkatesh, Mysore; Cheng, Fang; Sun, Bing; Ioniata, Iuliana; Anantharaman, Thomas; Hubbard, E Jane Albert; Pnueli, Amir; Harel, David; Chandru, Vijay; Hariharan, Ramesh; Wigler, Michael; Park, Frank; Lin, Shih-Chieh; Lazebnik, Yuri; Winkler, Franz; Cantor, Charles R; Carbone, Alessandra; Gromov, Mikhael

    2003-01-01

    We collaborate in a research program aimed at creating a rigorous framework, experimental infrastructure, and computational environment for understanding, experimenting with, manipulating, and modifying a diverse set of fundamental biological processes at multiple scales and spatio-temporal modes. The novelty of our research is based on an approach that (i) requires coevolution of experimental science and theoretical techniques and (ii) exploits a certain universality in biology guided by a parsimonious model of evolutionary mechanisms operating at the genomic level and manifesting at the proteomic, transcriptomic, phylogenic, and other higher levels. Our current program in "systems biology" endeavors to marry large-scale biological experiments with the tools to ponder and reason about large, complex, and subtle natural systems. To achieve this ambitious goal, ideas and concepts are combined from many different fields: biological experimentation, applied mathematical modeling, computational reasoning schemes, and large-scale numerical and symbolic simulations. From a biological viewpoint, the basic issues are many: (i) understanding common and shared structural motifs among biological processes; (ii) modeling biological noise due to interactions among a small number of key molecules or loss of synchrony; (iii) explaining the robustness of these systems in spite of such noise; and (iv) cataloging multistatic behavior and adaptation exhibited by many biological processes.

  10. ORBITAL MIGRATION OF LOW-MASS PLANETS IN EVOLUTIONARY RADIATIVE MODELS: AVOIDING CATASTROPHIC INFALL

    International Nuclear Information System (INIS)

    Lyra, Wladimir; Mac Low, Mordecai-Mark; Paardekooper, Sijme-Jan

    2010-01-01

    Outward migration of low-mass planets has recently been shown to be a possibility in non-barotropic disks. We examine the consequences of this result in evolutionary models of protoplanetary disks. Planet migration occurs toward equilibrium radii with zero torque. These radii themselves migrate inwards because of viscous accretion and photoevaporation. We show that as the surface density and temperature fall the planet orbital migration and disk depletion timescales eventually become comparable, with the precise timing depending on the mass of the planet. When this occurs, the planet decouples from the equilibrium radius. At this time, however, the gas surface density is already too low to drive substantial further migration. A higher mass planet, of 10 M + , can open a gap during the late evolution of the disk, and stops migrating. Low-mass planets, with 1 or 0.1 M + , released beyond 1 AU in our models avoid migrating into the star. Our results provide support for the reduced migration rates adopted in recent planet population synthesis models.

  11. A system dynamics model based on evolutionary game theory for green supply chain management diffusion among Chinese manufacturers

    DEFF Research Database (Denmark)

    Tian, Yihui; Govindan, Kannan; Zhu, Qinghua

    2014-01-01

    In this study, a system dynamics (SD) model is developed to guide the subsidy policies to promote the diffusion of green supply chain management (GSCM) in China. The relationships of stakeholders such as government, enterprises and consumers are analyzed through evolutionary game theory. Finally...

  12. Evolutionary dynamics of incubation periods.

    Science.gov (United States)

    Ottino-Loffler, Bertrand; Scott, Jacob G; Strogatz, Steven H

    2017-12-21

    The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease.

  13. Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model

    Science.gov (United States)

    Zhao, Taoran; Zhao, Xinghui; Liu, Ju; Meng, Yingying; Feng, Yingying; Fang, Ting; Zhang, Jinlong; Yang, Xiuxu; Li, Jianmin; Xu, Junjie; Chen, Wei

    2016-01-01

    Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents. PMID:26848687

  14. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Science.gov (United States)

    Regales, Lucia; Balak, Marissa N; Gong, Yixuan; Politi, Katerina; Sawai, Ayana; Le, Carl; Koutcher, Jason A; Solit, David B; Rosen, Neal; Zakowski, Maureen F; Pao, William

    2007-08-29

    The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer. To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M) alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M)-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M)-expressing animals develop tumors with longer latency than EGFR(L858R+T790M)-bearing mice and in the absence of additional kinase domain mutations. These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M) alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  15. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Lucia Regales

    2007-08-01

    Full Text Available The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer.To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M-expressing animals develop tumors with longer latency than EGFR(L858R+T790M-bearing mice and in the absence of additional kinase domain mutations.These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  16. Evolutionary Agent-based Models to design distributed water management strategies

    Science.gov (United States)

    Giuliani, M.; Castelletti, A.; Reed, P. M.

    2012-12-01

    There is growing awareness in the scientific community that the traditional centralized approach to water resources management, as described in much of the water resources literature, provides an ideal optimal solution, which is certainly useful to quantify the best physically achievable performance, but is generally inapplicable. Most real world water resources management problems are indeed characterized by the presence of multiple, distributed and institutionally-independent decision-makers. Multi-Agent Systems provide a potentially more realistic alternative framework to model multiple and self-interested decision-makers in a credible context. Each decision-maker can be represented by an agent who, being self-interested, acts according to local objective functions and produces negative externalities on system level objectives. Different levels of coordination can potentially be included in the framework by designing coordination mechanisms to drive the current decision-making structure toward the global system efficiency. Yet, the identification of effective coordination strategies can be particularly complex in modern institutional contexts and current practice is dependent on largely ad-hoc coordination strategies. In this work we propose a novel Evolutionary Agent-based Modeling (EAM) framework that enables a mapping of fully uncoordinated and centrally coordinated solutions into their relative "many-objective" tradeoffs using multiobjective evolutionary algorithms. Then, by analysing the conflicts between local individual agent and global system level objectives it is possible to more fully understand the causes, consequences, and potential solution strategies for coordination failures. Game-theoretic criteria have value for identifying the most interesting alternatives from a policy making point of view as well as the coordination mechanisms that can be applied to obtain these interesting solutions. The proposed approach is numerically tested on a

  17. Improved Assimilation of Streamflow and Satellite Soil Moisture with the Evolutionary Particle Filter and Geostatistical Modeling

    Science.gov (United States)

    Yan, Hongxiang; Moradkhani, Hamid; Abbaszadeh, Peyman

    2017-04-01

    Assimilation of satellite soil moisture and streamflow data into hydrologic models using has received increasing attention over the past few years. Currently, these observations are increasingly used to improve the model streamflow and soil moisture predictions. However, the performance of this land data assimilation (DA) system still suffers from two limitations: 1) satellite data scarcity and quality; and 2) particle weight degeneration. In order to overcome these two limitations, we propose two possible solutions in this study. First, the general Gaussian geostatistical approach is proposed to overcome the limitation in the space/time resolution of satellite soil moisture products thus improving their accuracy at uncovered/biased grid cells. Secondly, an evolutionary PF approach based on Genetic Algorithm (GA) and Markov Chain Monte Carlo (MCMC), the so-called EPF-MCMC, is developed to further reduce weight degeneration and improve the robustness of the land DA system. This study provides a detailed analysis of the joint and separate assimilation of streamflow and satellite soil moisture into a distributed Sacramento Soil Moisture Accounting (SAC-SMA) model, with the use of recently developed EPF-MCMC and the general Gaussian geostatistical approach. Performance is assessed over several basins in the USA selected from Model Parameter Estimation Experiment (MOPEX) and located in different climate regions. The results indicate that: 1) the general Gaussian approach can predict the soil moisture at uncovered grid cells within the expected satellite data quality threshold; 2) assimilation of satellite soil moisture inferred from the general Gaussian model can significantly improve the soil moisture predictions; and 3) in terms of both deterministic and probabilistic measures, the EPF-MCMC can achieve better streamflow predictions. These results recommend that the geostatistical model is a helpful tool to aid the remote sensing technique and the EPF-MCMC is a

  18. Restructuring of workflows to minimise errors via stochastic model checking: An automated evolutionary approach

    International Nuclear Information System (INIS)

    Herbert, L.T.; Hansen, Z.N.L.

    2016-01-01

    This paper presents a framework for the automated restructuring of stochastic workflows to reduce the impact of faults. The framework allows for the modelling of workflows by means of a formalised subset of the BPMN workflow language. We extend this modelling formalism to describe faults and incorporate an intention preserving stochastic semantics able to model both probabilistic- and non-deterministic behaviour. Stochastic model checking techniques are employed to generate the state-space of a given workflow. Possible improvements obtained by restructuring are measured by employing the framework's capacity for tracking real-valued quantities associated with states and transitions of the workflow. The space of possible restructurings of a workflow is explored by means of an evolutionary algorithm, where the goals for improvement are defined in terms of optimising quantities, typically employed to model resources, associated with a workflow. The approach is fully automated and only the modelling of the production workflows, potential faults and the expression of the goals require manual input. We present the design of a software tool implementing this framework and explore the practical utility of this approach through an industrial case study in which the risk of production failures and their impact are reduced by restructuring the workflow. - Highlights: • We present a framework which allows for the automated restructuring of workflows. • This framework seeks to minimise the impact of errors on the workflow. • We illustrate a scalable software implementation of this framework. • We explore the practical utility of this approach through an industry case. • The impact of errors can be substantially reduced by restructuring the workflow.

  19. Acidithiobacillus caldus sulfur oxidation model based on transcriptome analysis between the wild type and sulfur oxygenase reductase defective mutant.

    Directory of Open Access Journals (Sweden)

    Linxu Chen

    Full Text Available Acidithiobacillus caldus (A. caldus is widely used in bio-leaching. It gains energy and electrons from oxidation of elemental sulfur and reduced inorganic sulfur compounds (RISCs for carbon dioxide fixation and growth. Genomic analyses suggest that its sulfur oxidation system involves a truncated sulfur oxidation (Sox system (omitting SoxCD, non-Sox sulfur oxidation system similar to the sulfur oxidation in A. ferrooxidans, and sulfur oxygenase reductase (SOR. The complexity of the sulfur oxidation system of A. caldus generates a big obstacle on the research of its sulfur oxidation mechanism. However, the development of genetic manipulation method for A. caldus in recent years provides powerful tools for constructing genetic mutants to study the sulfur oxidation system.An A. caldus mutant lacking the sulfur oxygenase reductase gene (sor was created and its growth abilities were measured in media using elemental sulfur (S(0 and tetrathionate (K(2S(4O(6 as the substrates, respectively. Then, comparative transcriptome analysis (microarrays and real-time quantitative PCR of the wild type and the Δsor mutant in S(0 and K(2S(4O(6 media were employed to detect the differentially expressed genes involved in sulfur oxidation. SOR was concluded to oxidize the cytoplasmic elemental sulfur, but could not couple the sulfur oxidation with the electron transfer chain or substrate-level phosphorylation. Other elemental sulfur oxidation pathways including sulfur diooxygenase (SDO and heterodisulfide reductase (HDR, the truncated Sox pathway, and the S(4I pathway for hydrolysis of tetrathionate and oxidation of thiosulfate in A. caldus are proposed according to expression patterns of sulfur oxidation genes and growth abilities of the wild type and the mutant in different substrates media.An integrated sulfur oxidation model with various sulfur oxidation pathways of A. caldus is proposed and the features of this model are summarized.

  20. An Evolutionary Model of the Environmental Conditions that Shape the Development of Prosociality

    Directory of Open Access Journals (Sweden)

    Daniel Tumminelli O'Brien

    2014-04-01

    Full Text Available The current review presents a model for how prosocial development is driven by sociocognitive mechanisms that have been shaped by natural selection to translate critical environmental factors into locally adaptive levels of prosociality. This is done through a synthesis of two existing literatures. Evolutionary developmental psychologists have demonstrated a biological basis for the emergence of prosocial behavior early in youth, and work based on social learning theory has explored how social experiences can influence prosociality across development. The model forwarded organizes this latter literature in a way that is specific to how the biological mechanisms underpinning prosociality have evolved. This consists of two main psychological mechanisms. 1 A domain-specific program that is responsive to environmental factors that determine the relative success of different levels of prosociality. It uses the local prevalence of prosocial others (i.e., support and expectations for prosocial behavior (i.e., structure to guide prosocial development. 2 The domain-general process of cultural learning, by which youth adopt local social norms based on the examples of others. Implications and hypotheses are articulated for both the sociocognitive structure of the individual and the role of social contexts.

  1. An Evolutionary Game Theory Model of Revision-Resistant Motivations and Strategic Reasoning

    National Research Council Canada - National Science Library

    DeLancey, Craig

    2008-01-01

    Strong reciprocity and other forms of cooperation with non-kin in large groups and in one-time social interactions is difficult to explain with traditional economic or with simple evolutionary accounts...

  2. Dystrophin Hot-Spot Mutants Leading to Becker Muscular Dystrophy Insert More Deeply into Membrane Models than the Native Protein.

    Science.gov (United States)

    Ameziane-Le Hir, Sarah; Paboeuf, Gilles; Tascon, Christophe; Hubert, Jean-François; Le Rumeur, Elisabeth; Vié, Véronique; Raguénès-Nicol, Céline

    2016-07-26

    Dystrophin (DYS) is a membrane skeleton protein whose mutations lead to lethal Duchenne muscular dystrophy or to the milder Becker muscular dystrophy (BMD). One third of BMD "in-frame" exon deletions are located in the region that codes for spectrin-like repeats R16 to R21. We focused on four prevalent mutated proteins deleted in this area (called RΔ45-47, RΔ45-48, RΔ45-49, and RΔ45-51 according to the deleted exon numbers), analyzing protein/membrane interactions. Two of the mutants, RΔ45-48 and RΔ45-51, led to mild pathologies and displayed a similar triple coiled-coil structure as the full-length DYS R16-21, whereas the two others, RΔ45-47 and RΔ45-49, induced more severe pathologies and showed "fractional" structures unrelated to the normal one. To explore lipid packing, small unilamellar liposomes (SUVs) and planar monolayers were used at various initial surface pressures. The dissociation constants determined by microscale thermophoresis (MST) were much higher for the full-length DYS R161-21 than for the mutants; thus the wild type protein has weaker SUV binding. Comparing surface pressures after protein adsorption and analysis of atomic force microscopy images of mixed protein/lipid monolayers revealed that the mutants insert more into the lipid monolayer than the wild type does. In fact, in both models every deletion mutant showed more interactions with membranes than the full-length protein did. This means that mutations in the R16-21 part of dystrophin disturb the protein's molecular behavior as it relates to membranes, regardless of whether the accompanying pathology is mild or severe.

  3. Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.

    Science.gov (United States)

    Hebbar, Sarita; Khandelwal, Avinash; Jayashree, R; Hindle, Samantha J; Chiang, Yin Ning; Yew, Joanne Y; Sweeney, Sean T; Schwudke, Dominik

    2017-12-15

    Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD. © 2017 Hebbar et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

    Science.gov (United States)

    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

    2015-01-01

    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine. PMID:22544168

  5. Applications of the k – ω Model in Stellar Evolutionary Models

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan, E-mail: ly@ynao.ac.cn [Yunnan Observatories, Chinese Academy of Sciences, Kunming 650216 (China)

    2017-05-20

    The k – ω model for turbulence was first proposed by Kolmogorov. A new k – ω model for stellar convection was developed by Li, which could reasonably describe turbulent convection not only in the convectively unstable zone, but also in the overshooting regions. We revised the k – ω model by improving several model assumptions (including the macro-length of turbulence, convective heat flux, and turbulent mixing diffusivity, etc.), making it applicable not only for convective envelopes, but also for convective cores. Eight parameters are introduced in the revised k – ω model. It should be noted that the Reynolds stress (turbulent pressure) is neglected in the equation of hydrostatic support. We applied it into solar models and 5 M {sub ⊙} stellar models to calibrate the eight model parameters, as well as to investigate the effects of the convective overshooting on the Sun and intermediate mass stellar models.

  6. Ecological and evolutionary dynamics of a model facultative pathogen: Agrobacterium and crown gall disease of plants.

    Science.gov (United States)

    Barton, Ian S; Fuqua, Clay; Platt, Thomas G

    2018-01-01

    Many important pathogens maintain significant populations in highly disparate disease and non-disease environments. The consequences of this environmental heterogeneity in shaping the ecological and evolutionary dynamics of these facultative pathogens are incompletely understood. Agrobacterium tumefaciens, the causative agent for crown gall disease of plants has proven a productive model for many aspects of interactions between pathogens and their hosts and with other microbes. In this review, we highlight how this past work provides valuable context for the use of this system to examine how heterogeneity and transitions between disease and non-disease environments influence the ecology and evolution of facultative pathogens. We focus on several features common among facultative pathogens, such as the physiological remodelling required to colonize hosts from environmental reservoirs and the consequences of competition with host and non-host associated microbiota. In addition, we discuss how the life history of facultative pathogens likely often results in ecological tradeoffs associated with performance in disease and non-disease environments. These pathogens may therefore have different competitive dynamics in disease and non-disease environments and are subject to shifting selective pressures that can result in pathoadaptation or the within-host spread of avirulent phenotypes. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. An evolutionary attractor model for sapwood cross section in relation to leaf area.

    Science.gov (United States)

    Westoby, Mark; Cornwell, William K; Falster, Daniel S

    2012-06-21

    Sapwood cross-sectional area per unit leaf area (SA:LA) is an influential trait that plants coordinate with physical environment and with other traits. We develop theory for SA:LA and also for root surface area per leaf area (RA:LA) on the premise that plants maximizing the surplus of revenue over costs should have competitive advantage. SA:LA is predicted to increase in water-relations environments that reduce photosynthetic revenue, including low soil water potential, high water vapor pressure deficit (VPD), and low atmospheric CO(2). Because sapwood has costs, SA:LA adjustment does not completely offset difficult water relations. Where sapwood costs are large, as in tall plants, optimal SA:LA may actually decline with (say) high VPD. Large soil-to-root resistance caps the benefits that can be obtained from increasing SA:LA. Where a plant can adjust water-absorbing surface area of root per leaf area (RA:LA) as well as SA:LA, optimal RA:SA is not affected by VPD, CO(2) or plant height. If selection favours increased height more so than increased revenue-minus-cost, then height is predicted to rise substantially under improved water-relations environments such as high-CO(2) atmospheres. Evolutionary-attractor theory for SA:LA and RA:LA complements models that take whole-plant conductivity per leaf area as a parameter. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.

    Science.gov (United States)

    Clopath, Claudia; Badura, Aleksandra; De Zeeuw, Chris I; Brunel, Nicolas

    2014-05-21

    Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. Copyright © 2014 the authors 0270-6474/14/347203-13$15.00/0.

  9. Comparative and Evolutionary Analysis of Grass Pollen Allergens Using Brachypodium distachyon as a Model System.

    Directory of Open Access Journals (Sweden)

    Akanksha Sharma

    Full Text Available Comparative genomics have facilitated the mining of biological information from a genome sequence, through the detection of similarities and differences with genomes of closely or more distantly related species. By using such comparative approaches, knowledge can be transferred from the model to non-model organisms and insights can be gained in the structural and evolutionary patterns of specific genes. In the absence of sequenced genomes for allergenic grasses, this study was aimed at understanding the structure, organisation and expression profiles of grass pollen allergens using the genomic data from Brachypodium distachyon as it is phylogenetically related to the allergenic grasses. Combining genomic data with the anther RNA-Seq dataset revealed 24 pollen allergen genes belonging to eight allergen groups mapping on the five chromosomes in B. distachyon. High levels of anther-specific expression profiles were observed for the 24 identified putative allergen-encoding genes in Brachypodium. The genomic evidence suggests that gene encoding the group 5 allergen, the most potent trigger of hay fever and allergic asthma originated as a pollen specific orphan gene in a common grass ancestor of Brachypodium and Triticiae clades. Gene structure analysis showed that the putative allergen-encoding genes in Brachypodium either lack or contain reduced number of introns. Promoter analysis of the identified Brachypodium genes revealed the presence of specific cis-regulatory sequences likely responsible for high anther/pollen-specific expression. With the identification of putative allergen-encoding genes in Brachypodium, this study has also described some important plant gene families (e.g. expansin superfamily, EF-Hand family, profilins etc for the first time in the model plant Brachypodium. Altogether, the present study provides new insights into structural characterization and evolution of pollen allergens and will further serve as a base for their

  10. Multivariate dynamic linear models for estimating the effect of experimental interventions in an evolutionary operations setup in dairy herds

    DEFF Research Database (Denmark)

    Stygar, Anna Helena; Krogh, Mogens Agerbo; Kristensen, Troels

    2017-01-01

    Evolutionary operations is a method to exploit the association of often small changes in process variables, planned during systematic experimentation and occurring during the normal production flow, to production characteristics to find a way to alter the production process to be more efficient....... The objective of this study was to construct a tool to assess the intervention effect on milk production in an evolutionary operations setup. The method used for this purpose was a dynamic linear model (DLM) with Kalman filtering. The DLM consisted of parameters describing milk yield in a herd, individual cows...... bulk tank records. The presented model proved to be a flexible and dynamic tool, and it was successfully applied for systematic experimentation in dairy herds. The model can serve as a decision support tool for on-farm process optimization exploiting planned changes in process variables...

  11. Evolutionary Nephrology.

    Science.gov (United States)

    Chevalier, Robert L

    2017-05-01

    Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as "maladaptive." In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ~40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons), evolutionary selection for APOL1 mutations (that provide resistance to trypanosome infection, a tradeoff), and modern life experience (Western diet mismatch leading to diabetes and hypertension). Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo), developmental programming and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

  12. Development of a population of cancer cells: Observation and modeling by a Mixed Spatial Evolutionary Games approach.

    Science.gov (United States)

    Świerniak, Andrzej; Krześlak, Michał; Student, Sebastian; Rzeszowska-Wolny, Joanna

    2016-09-21

    Living cells, like whole living organisms during evolution, communicate with their neighbors, interact with the environment, divide, change their phenotypes, and eventually die. The development of specific ways of communication (through signaling molecules and receptors) allows some cellular subpopulations to survive better, to coordinate their physiological status, and during embryonal development to create tissues and organs or in some conditions to become tumors. Populations of cells cultured in vitro interact similarly, also competing for space and nutrients and stimulating each other to better survive or to die. The results of these intercellular interactions of different types seem to be good examples of biological evolutionary games, and have been the subjects of simulations by the methods of evolutionary game theory where individual cells are treated as players. Here we present examples of intercellular contacts in a population of living human cancer HeLa cells cultured in vitro and propose an evolutionary game theory approach to model the development of such populations. We propose a new technique termed Mixed Spatial Evolutionary Games (MSEG) which are played on multiple lattices corresponding to the possible cellular phenotypes which gives the possibility of simulating and investigating the effects of heterogeneity at the cellular level in addition to the population level. Analyses performed with MSEG suggested different ways in which cellular populations develop in the case of cells communicating directly and through factors released to the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Polymorphic Evolutionary Games.

    Science.gov (United States)

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    2011-03-01

    Tuberous sclerosis complex (TSC is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin or TSC2 (encodes tuberin genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242 in the tsc2 gene. This tsc2vu242 allele encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc2vu242 is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2vu242/vu242 homozygous zebrafish, and is moderately increased in tsc2vu242/+ heterozygotes. Forebrain neurons are poorly organized in tsc2vu242/vu242 homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in chimeric animals, tsc2vu242/vu242 mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.

  15. Intention recognition, commitment and their roles in the evolution of cooperation from artificial intelligence techniques to evolutionary game theory models

    CERN Document Server

    Han, The Anh

    2013-01-01

    This original and timely monograph describes a unique self-contained excursion that reveals to the readers the roles of two basic cognitive abilities, i.e. intention recognition and arranging commitments, in the evolution of cooperative behavior. This book analyses intention recognition, an important ability that helps agents predict others’ behavior, in its artificial intelligence and evolutionary computational modeling aspects, and proposes a novel intention recognition method. Furthermore, the book presents a new framework for intention-based decision making and illustrates several ways in which an ability to recognize intentions of others can enhance a decision making process. By employing the new intention recognition method and the tools of evolutionary game theory, this book introduces computational models demonstrating that intention recognition promotes the emergence of cooperation within populations of self-regarding agents. Finally, the book describes how commitment provides a pathway to the evol...

  16. A case study of bats and white-nose syndrome demonstrating how to model population viability with evolutionary effects.

    Science.gov (United States)

    Maslo, Brooke; Fefferman, Nina H

    2015-08-01

    Ecological factors generally affect population viability on rapid time scales. Traditional population viability analyses (PVA) therefore focus on alleviating ecological pressures, discounting potential evolutionary impacts on individual phenotypes. Recent studies of evolutionary rescue (ER) focus on cases in which severe, environmentally induced population bottlenecks trigger a rapid evolutionary response that can potentially reverse demographic threats. ER models have focused on shifting genetics and resulting population recovery, but no one has explored how to incorporate those findings into PVA. We integrated ER into PVA to identify the critical decision interval for evolutionary rescue (DIER) under which targeted conservation action should be applied to buffer populations undergoing ER against extinction from stochastic events and to determine the most appropriate vital rate to target to promote population recovery. We applied this model to little brown bats (Myotis lucifugus) affected by white-nose syndrome (WNS), a fungal disease causing massive declines in several North American bat populations. Under the ER scenario, the model predicted that the DIER period for little brown bats was within 11 years of initial WNS emergence, after which they stabilized at a positive growth rate (λ = 1.05). By comparing our model results with population trajectories of multiple infected hibernacula across the WNS range, we concluded that ER is a potential explanation of observed little brown bat population trajectories across multiple hibernacula within the affected range. Our approach provides a tool that can be used by all managers to provide testable hypotheses regarding the occurrence of ER in declining populations, suggest empirical studies to better parameterize the population genetics and conservation-relevant vital rates, and identify the DIER period during which management strategies will be most effective for species conservation. © 2015 Society for Conservation

  17. Induction of diploid gynogenesis in an evolutionary model organism, the three-spined stickleback (Gasterosteus aculeatus

    Directory of Open Access Journals (Sweden)

    Scharsack Jörn P

    2011-09-01

    Full Text Available Abstract Background Rapid advances in genomics have provided nearly complete genome sequences for many different species. However, no matter how the sequencing technology has improved, natural genetic polymorphism complicates the production of high quality reference genomes. To address this problem, researchers have tried using artificial modes of genome manipulation such as gynogenesis for fast production of inbred lines. Results Here, we present the first successful induction of diploid gynogenesis in an evolutionary model system, the three-spined sticklebacks (Gasterosteus aculeatus, using a combination of UV-irradiation of the sperm and heat shock (HS of the resulting embryo to inhibit the second meiotic division. Optimal UV irradiation of the sperm was established by exposing stickleback sperm to a UV- light source at various times. Heat shock parameters like temperature, duration, and time of initiation were tested by subjecting eggs fertilized with UV inactivated sperm 5, 10, 15, 20, 25, or 30 minutes post fertilization (mpf to 30°C, 34°C, or 38°C for 2, 4, 6 or 8 minutes. Gynogen yield was highest when stickleback eggs were activated with 2 minutes UV-irradiated sperm and received HS 5 mpf at 34°C for 4 minutes. Conclusions Diploid gynogenesis has been successfully performed in three-spined stickleback. This has been confirmed by microsatellite DNA analysis which revealed exclusively maternal inheritance in all gynogenetic fry tested. Ploidy verification by flow cytometry showed that gynogenetic embryos/larvae exhibiting abnormalities were haploids and those that developed normally were diploids, i.e., double haploids that can be raised until adult size.

  18. Induction of diploid gynogenesis in an evolutionary model organism, the three-spined stickleback (Gasterosteus aculeatus)

    Science.gov (United States)

    2011-01-01

    Background Rapid advances in genomics have provided nearly complete genome sequences for many different species. However, no matter how the sequencing technology has improved, natural genetic polymorphism complicates the production of high quality reference genomes. To address this problem, researchers have tried using artificial modes of genome manipulation such as gynogenesis for fast production of inbred lines. Results Here, we present the first successful induction of diploid gynogenesis in an evolutionary model system, the three-spined sticklebacks (Gasterosteus aculeatus), using a combination of UV-irradiation of the sperm and heat shock (HS) of the resulting embryo to inhibit the second meiotic division. Optimal UV irradiation of the sperm was established by exposing stickleback sperm to a UV- light source at various times. Heat shock parameters like temperature, duration, and time of initiation were tested by subjecting eggs fertilized with UV inactivated sperm 5, 10, 15, 20, 25, or 30 minutes post fertilization (mpf) to 30°C, 34°C, or 38°C for 2, 4, 6 or 8 minutes. Gynogen yield was highest when stickleback eggs were activated with 2 minutes UV-irradiated sperm and received HS 5 mpf at 34°C for 4 minutes. Conclusions Diploid gynogenesis has been successfully performed in three-spined stickleback. This has been confirmed by microsatellite DNA analysis which revealed exclusively maternal inheritance in all gynogenetic fry tested. Ploidy verification by flow cytometry showed that gynogenetic embryos/larvae exhibiting abnormalities were haploids and those that developed normally were diploids, i.e., double haploids that can be raised until adult size. PMID:21910888

  19. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  20. Fitness landscapes, heuristics and technological paradigms: a critique on random search models in evolutionary economics

    NARCIS (Netherlands)

    Frenken, K.

    2001-01-01

    The biological evolution of complex organisms, in which the functioning of genes is interdependent, has been analyzed as "hill-climbing" on NK fitness landscapes through random mutation and natural selection. In evolutionary economics, NK fitness landscapes have been used to simulate the evolution

  1. Evolutionary Nephrology

    Directory of Open Access Journals (Sweden)

    Robert L. Chevalier

    2017-05-01

    Full Text Available Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as “maladaptive.” In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or from evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ∼40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons, evolutionary selection for APOL1 mutations (which provide resistance to trypanosome infection, a tradeoff, and modern life experience (Western diet mismatch leading to diabetes and hypertension. Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout the life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo, developmental programming, and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

  2. A new ARMAX model based on evolutionary algorithm and particle swarm optimization for short-term load forecasting

    International Nuclear Information System (INIS)

    Wang, Bo; Tai, Neng-ling; Zhai, Hai-qing; Ye, Jian; Zhu, Jia-dong; Qi, Liang-bo

    2008-01-01

    In this paper, a new ARMAX model based on evolutionary algorithm and particle swarm optimization for short-term load forecasting is proposed. Auto-regressive (AR) and moving average (MA) with exogenous variables (ARMAX) has been widely applied in the load forecasting area. Because of the nonlinear characteristics of the power system loads, the forecasting function has many local optimal points. The traditional method based on gradient searching may be trapped in local optimal points and lead to high error. While, the hybrid method based on evolutionary algorithm and particle swarm optimization can solve this problem more efficiently than the traditional ways. It takes advantage of evolutionary strategy to speed up the convergence of particle swarm optimization (PSO), and applies the crossover operation of genetic algorithm to enhance the global search ability. The new ARMAX model for short-term load forecasting has been tested based on the load data of Eastern China location market, and the results indicate that the proposed approach has achieved good accuracy. (author)

  3. Evaluation of Pax6 mutant rat as a model for autism.

    Directory of Open Access Journals (Sweden)

    Toshiko Umeda

    Full Text Available Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey(2/+ rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI. In the present study, we further examined behaviors of rSey(2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV in rSey(2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey(2/+ rats likely have some phenotypic components of autism.

  4. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

    Directory of Open Access Journals (Sweden)

    Iva Simeonova

    2013-06-01

    Full Text Available Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53Δ31, a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53Δ31/Δ31 mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Heterozygous p53+/Δ31 mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53Δ31/Δ31 cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism.

  5. Assessing variation in life-history tactics within a population using mixture regression models: a practical guide for evolutionary ecologists.

    Science.gov (United States)

    Hamel, Sandra; Yoccoz, Nigel G; Gaillard, Jean-Michel

    2017-05-01

    Mixed models are now well-established methods in ecology and evolution because they allow accounting for and quantifying within- and between-individual variation. However, the required normal distribution of the random effects can often be violated by the presence of clusters among subjects, which leads to multi-modal distributions. In such cases, using what is known as mixture regression models might offer a more appropriate approach. These models are widely used in psychology, sociology, and medicine to describe the diversity of trajectories occurring within a population over time (e.g. psychological development, growth). In ecology and evolution, however, these models are seldom used even though understanding changes in individual trajectories is an active area of research in life-history studies. Our aim is to demonstrate the value of using mixture models to describe variation in individual life-history tactics within a population, and hence to promote the use of these models by ecologists and evolutionary ecologists. We first ran a set of simulations to determine whether and when a mixture model allows teasing apart latent clustering, and to contrast the precision and accuracy of estimates obtained from mixture models versus mixed models under a wide range of ecological contexts. We then used empirical data from long-term studies of large mammals to illustrate the potential of using mixture models for assessing within-population variation in life-history tactics. Mixture models performed well in most cases, except for variables following a Bernoulli distribution and when sample size was small. The four selection criteria we evaluated [Akaike information criterion (AIC), Bayesian information criterion (BIC), and two bootstrap methods] performed similarly well, selecting the right number of clusters in most ecological situations. We then showed that the normality of random effects implicitly assumed by evolutionary ecologists when using mixed models was often

  6. siRNA-mediated Erc gene silencing suppresses tumor growth in Tsc2 mutant renal carcinoma model.

    Science.gov (United States)

    Imamura, Osamu; Okada, Hiroaki; Takashima, Yuuki; Zhang, Danqing; Kobayashi, Toshiyuki; Hino, Okio

    2008-09-18

    Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery of siRNAs for stable treatment except short hairpin RNAs (shRNAs). On the other hand, there are many reports of systemic delivery of siRNAs for transient treatment using liposome carriers and others. With regard to shRNAs, a report showed fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Therefore, we decided to use original siRNA microspheres instead of shRNA for stable treatment of disease. In this study, we designed rat-specific siRNA sequences for Erc/mesothelin, which is a tumor-specific gene expressed in the Eker (Tsc2 mutant) rat model of hereditary renal cancer and confirmed the efficacy of gene silencing in vitro. Then, by using siRNA microspheres, we found that the suppression of Erc/mesothelin caused growth inhibition of Tsc2 mutant renal carcinoma cells in tumor implantation experiments in mice.

  7. Large fluctuations and fixation in evolutionary games

    International Nuclear Information System (INIS)

    Assaf, Michael; Mobilia, Mauro

    2010-01-01

    We study large fluctuations in evolutionary games belonging to the coordination and anti-coordination classes. The dynamics of these games, modeling cooperation dilemmas, is characterized by a coexistence fixed point separating two absorbing states. We are particularly interested in the problem of fixation that refers to the possibility that a few mutants take over the entire population. Here, the fixation phenomenon is induced by large fluctuations and is investigated by a semiclassical WKB (Wentzel–Kramers–Brillouin) theory generalized to treat stochastic systems possessing multiple absorbing states. Importantly, this method allows us to analyze the combined influence of selection and random fluctuations on the evolutionary dynamics beyond the weak selection limit often considered in previous works. We accurately compute, including pre-exponential factors, the probability distribution function in the long-lived coexistence state and the mean fixation time necessary for a few mutants to take over the entire population in anti-coordination games, and also the fixation probability in the coordination class. Our analytical results compare excellently with extensive numerical simulations. Furthermore, we demonstrate that our treatment is superior to the Fokker–Planck approximation when the selection intensity is finite

  8. Evolutionary thinking

    Science.gov (United States)

    Hunt, Tam

    2014-01-01

    Evolution as an idea has a lengthy history, even though the idea of evolution is generally associated with Darwin today. Rebecca Stott provides an engaging and thoughtful overview of this history of evolutionary thinking in her 2013 book, Darwin's Ghosts: The Secret History of Evolution. Since Darwin, the debate over evolution—both how it takes place and, in a long war of words with religiously-oriented thinkers, whether it takes place—has been sustained and heated. A growing share of this debate is now devoted to examining how evolutionary thinking affects areas outside of biology. How do our lives change when we recognize that all is in flux? What can we learn about life more generally if we study change instead of stasis? Carter Phipps’ book, Evolutionaries: Unlocking the Spiritual and Cultural Potential of Science's Greatest Idea, delves deep into this relatively new development. Phipps generally takes as a given the validity of the Modern Synthesis of evolutionary biology. His story takes us into, as the subtitle suggests, the spiritual and cultural implications of evolutionary thinking. Can religion and evolution be reconciled? Can evolutionary thinking lead to a new type of spirituality? Is our culture already being changed in ways that we don't realize by evolutionary thinking? These are all important questions and Phipps book is a great introduction to this discussion. Phipps is an author, journalist, and contributor to the emerging “integral” or “evolutionary” cultural movement that combines the insights of Integral Philosophy, evolutionary science, developmental psychology, and the social sciences. He has served as the Executive Editor of EnlightenNext magazine (no longer published) and more recently is the co-founder of the Institute for Cultural Evolution, a public policy think tank addressing the cultural roots of America's political challenges. What follows is an email interview with Phipps. PMID:26478766

  9. Evolutionary Demography

    DEFF Research Database (Denmark)

    Levitis, Daniel

    2015-01-01

    of biological and cultural evolution. Demographic variation within and among human populations is influenced by our biology, and therefore by natural selection and our evolutionary background. Demographic methods are necessary for studying populations of other species, and for quantifying evolutionary fitness......Demography is the quantitative study of population processes, while evolution is a population process that influences all aspects of biological organisms, including their demography. Demographic traits common to all human populations are the products of biological evolution or the interaction...

  10. A spontaneous and novel Pax3 mutant mouse that models Waardenburg syndrome and neural tube defects.

    Science.gov (United States)

    Ohnishi, Tetsuo; Miura, Ikuo; Ohba, Hisako; Shimamoto, Chie; Iwayama, Yoshimi; Wakana, Shigeharu; Yoshikawa, Takeo

    2017-04-05

    Genes responsible for reduced pigmentation phenotypes in rodents are associated with human developmental defects, such as Waardenburg syndrome, where patients display congenital deafness along with various abnormalities mostly related to neural crest development deficiency. In this study, we identified a spontaneous mutant mouse line Rwa, which displays variable white spots on mouse bellies and white digits and tail, on a C57BL/6N genetic background. Curly tail and spina bifida were also observed, although at a lower penetrance. These phenotypes were dominantly inherited by offspring. We searched for the genetic mechanism of the observed phenotypes. We harnessed a rapid mouse gene mapping system newly developed in our laboratories to identify a responsible gene. We detected a region within chromosome 1 as a probable locus for the causal mutation. Dense mapping using interval markers narrowed the locus down to a 670-kbp region, containing four genes including Pax3, a gene known to be implicated in the types I and III Waardenburg syndrome. Extensive mutation screening of Pax3 detected an 841-bp deletion, spanning the promoter region and intron 1 of the gene. The defective allele of Pax3, named Pax3 Rwa , lacked the first coding exon and co-segregated perfectly with the phenotypes, confirming its causal nature. The genetic background of Rwa mice is almost identical to that of inbred C57BL/6N. These results highlight Pax3 Rwa mice as a beneficial tool for analyzing biological processes involving Pax3, in particular the development and migration of neural crest cells and melanocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Models for Evolutionary Algorithms and Their Applications in System Identification and Control Optimization

    DEFF Research Database (Denmark)

    Ursem, Rasmus Kjær

    population and many generations, which essentially turns the problem into a series of related static problems. To our surprise, the control problem could easily be solved when optimized like this. To further examine this, we compared the EA with a particle swarm and a local search approach, which we...... simulate an evolutionary process where the goal is to evolve solutions by means of crossover, mutation, and selection based on their quality (fitness) with respect to the optimization problem at hand. Evolutionary algorithms (EAs) are highly relevant for industrial applications, because they are capable...... of handling problems with non-linear constraints, multiple objectives, and dynamic components – properties that frequently appear in real-world problems. This thesis presents research in three fundamental areas of EC; fitness function design, methods for parameter control, and techniques for multimodal...

  12. Protecting the larger fish: an ecological, economical and evolutionary analysis using a demographic model

    DEFF Research Database (Denmark)

    Verdiell, Nuria Calduch

    . Recently, there is increasing evidence that this size-selective fishing reduces the chances of maintaining populations at levels sufficient to produce maximum sustainable yields, the chances of recovery/rebuilding populations that have been depleted/collapsed and may causes rapid evolutionary changes...... and the consequent changes in yield. We attempt to evaluate the capability of the larger fish to mitigate the evolutionary change on life-history traits caused by fishing, while also maintaining a sustainable annual yield. This is achieved by calculating the expected selection response on three life-history traits......Many marine fish stocks are reported as overfished on a global scale. This overfishing not only removes fish biomass, but also causes dramatic changes in the age and size structure of fish stocks. In particular, targeting of the larger individuals truncates the age and size structure of stocks...

  13. Citizen science reveals unexpected continental-scale evolutionary change in a model organism.

    Directory of Open Access Journals (Sweden)

    Jonathan Silvertown

    2011-04-01

    Full Text Available Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis. This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate.

  14. An Evolutionary Cascade Model for Sauropod Dinosaur Gigantism - Overview, Update and Tests

    OpenAIRE

    Sander, P. Martin

    2013-01-01

    Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutiona...

  15. Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism.

    Science.gov (United States)

    Dhamne, Sameer C; Silverman, Jill L; Super, Chloe E; Lammers, Stephen H T; Hameed, Mustafa Q; Modi, Meera E; Copping, Nycole A; Pride, Michael C; Smith, Daniel G; Rotenberg, Alexander; Crawley, Jacqueline N; Sahin, Mustafa

    2017-01-01

    Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant ( Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each

  16. A New Model of the Early Paleozoic Tectonics and Evolutionary History in the Northern Qinling, China

    Science.gov (United States)

    Dong, Yunpeng; Zhang, Guowei; Yang, Zhao; Qu, Hongjun; Liu, Xiaoming

    2010-05-01

    The Qinling Orogenic Belt extends from the Qinling Mountains in the west to the Dabie Mountains in the east. It lies between the North China and South China Blocks, and is bounded on the north by the Lushan fault and on the south by the Mianlue-Bashan-Xiangguang fault (Zhang et al., 2000). The Qinling Orogenic Belt itself is divided into the North and South Qinling Terranes by the Shangdan suture zone. Although the Shangdan zone is thought to represent the major suture separating the two blocks, there still exists debate about the timing and mechanism of convergence between these two blocks. For instance, some authors suggested an Early Paleozoic collision between the North China Block and South China Block (Ren et al., 1991; Kroner et al., 1993; Zhai et al., 1998). Others postulated left-lateral strike-slip faulting along the Shangdan suture at ca. 315 Ma and inferred a pre-Devonian collision between the two blocks (Mattauer et al., 1985; Xu et al., 1988). Geochemistry of fine-grained sediments in the Qinling Mountains was used to argue for a Silurian-Devonian collision (Gao et al., 1995). A Late Triassic collision has also been proposed (Sengor, 1985; Hsu et al., 1987; Wang et al., 1989), based on the formation of ultrahigh-pressure metamorphic rocks in the easternmost part of the Qinling Orogenic Belt at ~230 Ma (e.g., Li et al., 1993; Ames et al., 1996). Paleomagnetic data favor a Late Triassic-Middle Jurassic amalgamation of the North China and South China Blocks (Zhao and Coe, 1987; Enkin et al., 1992). It is clear that most authors thought that the Qinling Mountains are a collisional orogen, even they have different methods about the timing of the orogeny. Based on new detailed investigations, we propose a new model of the Early Paleozoic Tectonics and Evolutionary History between the North China and South China Blocks along the Shangdan Suture. The Shangdan suture is marked by a great number of ophiolites, island-arc volcanic rocks and other related rock

  17. Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation

    Directory of Open Access Journals (Sweden)

    Sabatini Mary E

    2011-05-01

    Full Text Available Abstract Background Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function. Methods We utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization (progesterone production in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype. Conclusions Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their

  18. Evolutionary Dynamics and Diversity in Microbial Populations

    Science.gov (United States)

    Thompson, Joel; Fisher, Daniel

    2013-03-01

    Diseases such as flu and cancer adapt at an astonishing rate. In large part, viruses and cancers are so difficult to prevent because they are continually evolving. Controlling such ``evolutionary diseases'' requires a better understanding of the underlying evolutionary dynamics. It is conventionally assumed that adaptive mutations are rare and therefore will occur and sweep through the population in succession. Recent experiments using modern sequencing technologies have illuminated the many ways in which real population sequence data does not conform to the predictions of conventional theory. We consider a very simple model of asexual evolution and perform simulations in a range of parameters thought to be relevant for microbes and cancer. Simulation results reveal complex evolutionary dynamics typified by competition between lineages with different sets of adaptive mutations. This dynamical process leads to a distribution of mutant gene frequencies different than expected under the conventional assumption that adaptive mutations are rare. Simulated gene frequencies share several conspicuous features with data collected from laboratory-evolved yeast and the worldwide population of influenza.

  19. A new chronostratigraphical and evolutionary model for La Gomera: Implications for the overall evolution of the Canarian Archipelago

    OpenAIRE

    Ancochea Soto, Eumenio; Hernán, F.; Huertas Coronel, María José; Brandle, J.L.; Herrera, R.

    2006-01-01

    A review of the general volcano-stratigraphy and geochronology of La Gomera, one of the lesser known Canary Islands, has led to the establishment of a new evolutionary model. The oldest edifice corresponds to the submarine stage built up between 20 and 15 Ma. The construction of the Submarine Edifice was followed by an important break in the activity (about 4 Ma) and deep erosion of the edifice. About 10.5 Ma ago, the main present-day edifice (the Old Edifice 10.5–6.4 Ma) emerged, which was a...

  20. An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope.

    Directory of Open Access Journals (Sweden)

    Art F Y Poon

    2007-11-01

    Full Text Available The third variable loop (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1 that founder effects in the evolutionary history of the sequences can be ignored, and; (2 that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%-40%. Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to

  1. CDMetaPOP: An individual-based, eco-evolutionary model for spatially explicit simulation of landscape demogenetics

    Science.gov (United States)

    Landguth, Erin L; Bearlin, Andrew; Day, Casey; Dunham, Jason B.

    2016-01-01

    1. Combining landscape demographic and genetics models offers powerful methods for addressing questions for eco-evolutionary applications.2. Using two illustrative examples, we present Cost–Distance Meta-POPulation, a program to simulate changes in neutral and/or selection-driven genotypes through time as a function of individual-based movement, complex spatial population dynamics, and multiple and changing landscape drivers.3. Cost–Distance Meta-POPulation provides a novel tool for questions in landscape genetics by incorporating population viability analysis, while linking directly to conservation applications.

  2. An Evolutionary Robotics Approach to the Control of Plant Growth and Motion: Modeling Plants and Crossing the Reality Gap

    DEFF Research Database (Denmark)

    Wahby, Mostafa; Hofstadler, Daniel Nicolas; Heinrich, Mary Katherine

    2016-01-01

    The self-organizing bio-hybrid collaboration of robots and natural plants allows for a variety of interesting applications. As an example we investigate how robots can be used to control the growth and motion of a natural plant, using LEDs to provide stimuli. We follow an evolutionary robotics...... approach where task performance is determined by monitoring the plant's reaction. First, we do initial plant experiments with simple, predetermined controllers. Then we use image sampling data as a model of the dynamics of the plant tip xy position. Second, we use this approach to evolve robot controllers...

  3. Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model.

    Science.gov (United States)

    Kamili, Saleem; Sozzi, Vitini; Thompson, Geoff; Campbell, Katie; Walker, Christopher M; Locarnini, Stephen; Krawczynski, Krzysztof

    2009-05-01

    Hepatitis B virus (HBV) mutants resistant to treatment with nucleoside or nucleotide analogs and those with the ability to escape from HBV-neutralizing antibody have the potential to infect HBV-vaccinated individuals. To address this potential serious public health challenge, we tested the efficacy of immunity induced by a commercial hepatitis B vaccine against a tissue culture-derived, clonal HBV polymerase mutant in HBV seronegative chimpanzees. The polymerase gene mutant contained a combination of three mutations (rtV173L, rtL180M, rtM204V), two of which resulted in changes to the overlapping viral envelope of the hepatitis B surface antigen (sE164D, sI195M). Prior to the HBV mutant challenge of vaccinated chimpanzees, we established virologic, serologic, and pathologic characteristics of infections resulting from intravenous inoculation of the HBV polymerase gene mutant and the sG145R vaccine-escape surface gene mutant. Cloning and sequencing experiments determined that the three mutations in the polymerase gene mutant remained stable and that the single mutation in the surface gene mutant reverted to the wild-type sequence. Immunological evidence of HBV replication was observed in the vaccinated chimpanzees after challenge with the polymerase gene mutant as well as after rechallenge with serum-derived wild-type HBV (5,000 chimpanzee infectious doses administered intravenously), despite robust humoral and cellular anti-HBV immune responses after hepatitis B vaccination. Our data showing successful experimental infection by HBV mutants despite the presence of high anti-HBs levels considered protective in the vaccinated host are consistent with clinical reports on breakthrough infection in anti-HBs-positive patients infected with HBV mutants. In the absence of a protective humoral immunity, adaptive cellular immune responses elicited by infection may limit HBV replication and persistence.

  4. Evolutionary Expectations

    DEFF Research Database (Denmark)

    Nash, Ulrik William

    2014-01-01

    , they are correlated among people who share environments because these individuals satisfice within their cognitive bounds by using cues in order of validity, as opposed to using cues arbitrarily. Any difference in expectations thereby arise from differences in cognitive ability, because two individuals with identical...... cognitive bounds will perceive business opportunities identically. In addition, because cues provide information about latent causal structures of the environment, changes in causality must be accompanied by changes in cognitive representations if adaptation is to be maintained. The concept of evolutionary......The concept of evolutionary expectations descends from cue learning psychology, synthesizing ideas on rational expectations with ideas on bounded rationality, to provide support for these ideas simultaneously. Evolutionary expectations are rational, but within cognitive bounds. Moreover...

  5. [Evolutionary medicine].

    Science.gov (United States)

    Wjst, M

    2013-12-01

    Evolutionary medicine allows new insights into long standing medical problems. Are we "really stoneagers on the fast lane"? This insight might have enormous consequences and will allow new answers that could never been provided by traditional anthropology. Only now this is made possible using data from molecular medicine and systems biology. Thereby evolutionary medicine takes a leap from a merely theoretical discipline to practical fields - reproductive, nutritional and preventive medicine, as well as microbiology, immunology and psychiatry. Evolutionary medicine is not another "just so story" but a serious candidate for the medical curriculum providing a universal understanding of health and disease based on our biological origin. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Evolutionary Awareness

    Directory of Open Access Journals (Sweden)

    Gregory Gorelik

    2014-10-01

    Full Text Available In this article, we advance the concept of “evolutionary awareness,” a metacognitive framework that examines human thought and emotion from a naturalistic, evolutionary perspective. We begin by discussing the evolution and current functioning of the moral foundations on which our framework rests. Next, we discuss the possible applications of such an evolutionarily-informed ethical framework to several domains of human behavior, namely: sexual maturation, mate attraction, intrasexual competition, culture, and the separation between various academic disciplines. Finally, we discuss ways in which an evolutionary awareness can inform our cross-generational activities—which we refer to as “intergenerational extended phenotypes”—by helping us to construct a better future for ourselves, for other sentient beings, and for our environment.

  7. Genome-scale metabolic model of the fission yeast Schizosaccharomyces pombe and the reconciliation of in silico/in vivo mutant growth

    Science.gov (United States)

    2012-01-01

    Background Over the last decade, the genome-scale metabolic models have been playing increasingly important roles in elucidating metabolic characteristics of biological systems for a wide range of applications including, but not limited to, system-wide identification of drug targets and production of high value biochemical compounds. However, these genome-scale metabolic models must be able to first predict known in vivo phenotypes before it is applied towards these applications with high confidence. One benchmark for measuring the in silico capability in predicting in vivo phenotypes is the use of single-gene mutant libraries to measure the accuracy of knockout simulations in predicting mutant growth phenotypes. Results Here we employed a systematic and iterative process, designated as Reconciling In silico/in vivo mutaNt Growth (RING), to settle discrepancies between in silico prediction and in vivo observations to a newly reconstructed genome-scale metabolic model of the fission yeast, Schizosaccharomyces pombe, SpoMBEL1693. The predictive capabilities of the genome-scale metabolic model in predicting single-gene mutant growth phenotypes were measured against the single-gene mutant library of S. pombe. The use of RING resulted in improving the overall predictive capability of SpoMBEL1693 by 21.5%, from 61.2% to 82.7% (92.5% of the negative predictions matched the observed growth phenotype and 79.7% the positive predictions matched the observed growth phenotype). Conclusion This study presents validation and refinement of a newly reconstructed metabolic model of the yeast S. pombe, through improving the metabolic model’s predictive capabilities by reconciling the in silico predicted growth phenotypes of single-gene knockout mutants, with experimental in vivo growth data. PMID:22631437

  8. A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

    Directory of Open Access Journals (Sweden)

    Edward Rockenstein

    Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

  9. Use of Transgenic and Mutant Animal Models in the Study of Heterocyclic Amine-induced Mutagenesis and Carcinogenesis

    Science.gov (United States)

    Dashwood, Roderick H.

    2008-01-01

    Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptΔ transgenics, XPA−/−, XPC−/−, Msh2+/−, Msh2−/− and p53+/− knock-outs, Apc mutant mice (ApcΔ716, Apc1638N, Apcmin), and A33ΔNβ-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac. PMID:12542973

  10. Evolutionary robotics

    Indian Academy of Sciences (India)

    In evolutionary robotics, a suitable robot control system is developed automatically through evolution due to the interactions between the robot and its environment. It is a complicated task, as the robot and the environment constitute a highly dynamical system. Several methods have been tried by various investigators to ...

  11. Analysis of Urban Car Owners Commute Mode Choice Based on Evolutionary Game Model

    Directory of Open Access Journals (Sweden)

    Huawei Gong

    2015-01-01

    Full Text Available With the aggravation of the traffic congestion in the city, car owners will have to give up commuting with private cars and take the public transportation instead. The paper uses the replication dynamic mechanism to simulate the learning and adjustment mechanism of the automobile owners commuting mode selection. The evolutionary stable strategy is used to describe the long-term evolution of competition game trend. Finally we simulate equilibrium and stability of an evolution of the game under a payoff imbalance situation. The research shows that a certain proportion of car owners will choose public transit under the pressure of public transport development and heavy traffic, and the proportion will be closely related to the initial conditions and urban transportation development policy.

  12. Evolutionary Graphs with Frequency Dependent Fitness

    Science.gov (United States)

    Nie, Pu-Yan; Zhang, Pei-Ai

    Evolutionary graph theory was recently proposed by Lieberman et al. in 2005. In the previous papers about evolutionary graphs (EGs), the fitness of the residents in the EGs is in general assumed to be unity, and the fitness of a mutant is assumed to be a constant r. We aim to extend EG to general cases in this paper, namely, the fitness of a mutant is heavily dependent upon frequency. The corresponding properties for these new EGs are analyzed, and the fixation probability is obtained for large population.

  13. Early Postnatal but Not Late Adult Neurogenesis Is Impaired in the Pitx3-Mutant Animal Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Moritz D. Brandt

    2017-08-01

    Full Text Available The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD. As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ and dentate gyrus (DG. Here we examined adult hippocampal neurogenesis in the Pitx3-mutant mouse model of PD (aphakia mice, which phenotypically shows a selective embryonic degeneration of dopamine neurons within the SN and to a smaller extent in the ventral tegmental area (VTA. Proliferating cells were labeled with BrdU in aphakia mice and healthy controls from 3 to 42 weeks of age. Three weeks old mutant mice showed an 18% reduction of proliferating cells in the DG and of 26% in the SVZ. Not only proliferation but also the number of new neurons was impaired in young aphakia mice resulting in 33% less newborn cells 4 weeks after BrdU-labeling. Remarkably, however, the decline in the number of proliferating cells in the neurogenic regions vanished in older animals (8–42 weeks indicating that aging masks the effect of dopamine depletion on adult neurogenesis. Region specific reduction in precursor cells proliferation correlated with the extent of dopaminergic degeneration in mesencephalic subregions (VTA and SN, which supports the theory of age- and region-dependent regulatory effects of dopaminergic projections. Physiological stimulation of adult neurogenesis by physical activity (wheel running almost doubled the number of proliferating cells in the dentate gyrus of 8 weeks old aphakia mice to a number comparable to that of wild-type mice, abolishing the slight

  14. Evolutionary aspects of non-cell-autonomous regulation in vascular plants: structural background and models to study

    Directory of Open Access Journals (Sweden)

    Anastasiia I. Evkaikina

    2014-02-01

    Full Text Available Plasmodesmata (PD serve for the exchange of information in form of miRNA, proteins and mRNA between adjacent cells in the course of plant development. This fundamental role of PD is well established in angiosperms but has not yet been traced back to the evolutionary ancient plant taxa where functional studies lag behind studies of PD structure and ontogenetic origin. There is convincing evidence that the ability to form secondary (post-cytokinesis PD, which can connect any adjacent cells, contrary to primary PD which form during cytokinesis and link only cells of the same lineage, appeared in the evolution of higher plants at least twice: in seed plants and in some representatives of the Lycopodiophyta. The (inability to form secondary PD is manifested in the symplastic organization of the shoot apical meristem (SAM which in most taxa of seedless vascular plants differs dramatically from that in seed plants. Lycopodiophyta appear to be suitable models to analyze the transport of developmental regulators via PD in SAMs with symplastic organization both different from, as well as analogous to, that in angiosperms, and to understand the evolutionary aspects of the role of this transport in the morphogenesis of vascular plant taxa.

  15. Molecular data and ecological niche modelling reveal a highly dynamic evolutionary history of the East Asian Tertiary relict Cercidiphyllum (Cercidiphyllaceae).

    Science.gov (United States)

    Qi, Xin-Shuai; Chen, Chen; Comes, Hans Peter; Sakaguchi, Shota; Liu, Yi-Hui; Tanaka, Nobuyuki; Sakio, Hitoshi; Qiu, Ying-Xiong

    2012-10-01

    East Asia's temperate deciduous forests served as sanctuary for Tertiary relict trees, but their ages and response to past climate change remain largely unknown. To address this issue, we elucidated the evolutionary and population demographic history of Cercdiphyllum, comprising species in China/Japan (Cercdiphyllum japonicum) and central Japan (Cercdiphyllum magnificum). Fifty-three populations were genotyped using chloroplast and ribosomal DNA sequences and microsatellite loci to assess molecular structure and diversity in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modelling. Late Tertiary climate cooling was reflected in a relatively recent speciation event, dated at the Mio-/Pliocene boundary. During glacials, the warm-temperate C. japonicum experienced massive habitat losses in some areas (north-central China/north Japan) but increases in others (southwest/-east China, East China Sea landbridge, south Japan). In China, the Sichuan Basin and/or the middle-Yangtze were source areas of postglacial northward recolonization; in Japan, this may have been facilitated through introgressive hybridization with the cool-temperate C. magnificum. Our findings challenge the notion of relative evolutionary and demographic stability of Tertiary relict trees, and may serve as a guideline for assessing the impact of Neogene climate change on the evolution and distribution of East Asian temperate plants. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  16. Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK.

    Science.gov (United States)

    Wang, T H; Wang, S Y; Wang, X D; Jiang, H Q; Yang, Y Q; Wang, Y; Cheng, J L; Zhang, C T; Liang, W W; Feng, H L

    2018-05-21

    Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. A new stellar spectrum interpolation algorithm and its application to Yunnan-III evolutionary population synthesis models

    Science.gov (United States)

    Cheng, Liantao; Zhang, Fenghui; Kang, Xiaoyu; Wang, Lang

    2018-05-01

    In evolutionary population synthesis (EPS) models, we need to convert stellar evolutionary parameters into spectra via interpolation in a stellar spectral library. For theoretical stellar spectral libraries, the spectrum grid is homogeneous on the effective-temperature and gravity plane for a given metallicity. It is relatively easy to derive stellar spectra. For empirical stellar spectral libraries, stellar parameters are irregularly distributed and the interpolation algorithm is relatively complicated. In those EPS models that use empirical stellar spectral libraries, different algorithms are used and the codes are often not released. Moreover, these algorithms are often complicated. In this work, based on a radial basis function (RBF) network, we present a new spectrum interpolation algorithm and its code. Compared with the other interpolation algorithms that are used in EPS models, it can be easily understood and is highly efficient in terms of computation. The code is written in MATLAB scripts and can be used on any computer system. Using it, we can obtain the interpolated spectra from a library or a combination of libraries. We apply this algorithm to several stellar spectral libraries (such as MILES, ELODIE-3.1 and STELIB-3.2) and give the integrated spectral energy distributions (ISEDs) of stellar populations (with ages from 1 Myr to 14 Gyr) by combining them with Yunnan-III isochrones. Our results show that the differences caused by the adoption of different EPS model components are less than 0.2 dex. All data about the stellar population ISEDs in this work and the RBF spectrum interpolation code can be obtained by request from the first author or downloaded from http://www1.ynao.ac.cn/˜zhangfh.

  18. Spontaneous shaker rat mutant - a new model for X-linked tremor/ataxia.

    Science.gov (United States)

    Figueroa, Karla P; Paul, Sharan; Calì, Tito; Lopreiato, Raffaele; Karan, Sukanya; Frizzarin, Martina; Ames, Darren; Zanni, Ginevra; Brini, Marisa; Dansithong, Warunee; Milash, Brett; Scoles, Daniel R; Carafoli, Ernesto; Pulst, Stefan M

    2016-05-01

    The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca(2+) transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3(R35C) function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes. © 2016. Published by The Company of Biologists Ltd.

  19. Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia

    Directory of Open Access Journals (Sweden)

    Karla P. Figueroa

    2016-05-01

    Full Text Available The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF/Brown Norwegian (BN F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm. In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R to cysteine (C change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3 gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes.

  20. Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia

    Science.gov (United States)

    Figueroa, Karla P.; Paul, Sharan; Calì, Tito; Lopreiato, Raffaele; Karan, Sukanya; Frizzarin, Martina; Ames, Darren; Zanni, Ginevra; Brini, Marisa; Dansithong, Warunee; Milash, Brett; Scoles, Daniel R.; Carafoli, Ernesto; Pulst, Stefan M.

    2016-01-01

    ABSTRACT The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes. PMID:27013529

  1. Vision-guided ocular growth in a mutant chicken model with diminished visual acuity.

    Science.gov (United States)

    Ritchey, Eric R; Zelinka, Christopher; Tang, Junhua; Liu, Jun; Code, Kimberly A; Petersen-Jones, Simon; Fischer, Andy J

    2012-09-01

    Visual experience is known to guide ocular growth. We tested the hypothesis that vision-guided ocular growth is disrupted in a model system with diminished visual acuity. We examine whether ocular elongation is influenced by form-deprivation (FD) and lens-imposed defocus in the Retinopathy, Globe Enlarged (RGE) chicken. Young RGE chicks have poor visual acuity, without significant retinal pathology, resulting from a mutation in guanine nucleotide-binding protein β3 (GNB3), also known as transducin β3 or Gβ3. The mutation in GNB3 destabilizes the protein and causes a loss of Gβ3 from photoreceptors and ON-bipolar cells (Ritchey et al., 2010). FD increased ocular elongation in RGE eyes in a manner similar to that seen in wild-type (WT) eyes. By comparison, the excessive ocular elongation that results from hyperopic defocus was increased, whereas myopic defocus failed to significantly decrease ocular elongation in RGE eyes. Brief daily periods of unrestricted vision interrupting FD prevented ocular elongation in RGE chicks in a manner similar to that seen in WT chicks. Glucagonergic amacrine cells differentially expressed the immediate early gene Egr1 in response to growth-guiding stimuli in RGE retinas, but the defocus-dependent up-regulation of Egr1 was lesser in RGE retinas compared to that of WT retinas. We conclude that high visual acuity, and the retinal signaling mediated by Gβ3, is not required for emmetropization and the excessive ocular elongation caused by FD and hyperopic defocus. However, the loss of acuity and Gβ3 from RGE retinas causes enhanced responses to hyperopic defocus and diminished responses to myopic defocus. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Kinetic modeling of batch fermentation for Populus hydrolysate tolerant mutant and wild type strains of Clostridium thermocellum.

    Science.gov (United States)

    Linville, Jessica L; Rodriguez, Miguel; Mielenz, Jonathan R; Cox, Chris D

    2013-11-01

    The extent of inhibition of two strains of Clostridium thermocellum by a Populus hydrolysate was investigated. A Monod-based model of wild type (WT) and Populus hydrolysate tolerant mutant (PM) strains of the cellulolytic bacterium C. thermocellum was developed to quantify growth kinetics in standard media and the extent of inhibition to a Populus hydrolysate. The PM was characterized by a higher growth rate (μmax=1.223 vs. 0.571 h(-1)) and less inhibition (KI,gen=0.991 vs. 0.757) in 10% v/v Populus hydrolysate compared to the WT. In 17.5% v/v Populus hydrolysate inhibition of PM increased slightly (KI,gen=0.888), whereas the WT was strongly inhibited and did not grow in a reproducible manner. Of the individual inhibitors tested, 4-hydroxybenzoic acid was the most inhibitory, followed by galacturonic acid. The PM did not have a greater ability to detoxify the hydrolysate than the WT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

    Science.gov (United States)

    Garrido-Allepuz, Carlos; González-Lamuño, Domingo; Ros, Maria A

    2012-01-01

    Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i) a primary defect in the generation of caudal mesoderm, ii) a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

  4. Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

    Directory of Open Access Journals (Sweden)

    Carlos Garrido-Allepuz

    Full Text Available Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i a primary defect in the generation of caudal mesoderm, ii a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

  5. A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model.

    Science.gov (United States)

    Wang, Fang; Travins, Jeremy; Lin, Zhizhong; Si, Yaguang; Chen, Yue; Powe, Josh; Murray, Stuart; Zhu, Dongwei; Artin, Erin; Gross, Stefan; Santiago, Stephanie; Steadman, Mya; Kernytsky, Andrew; Straley, Kimberly; Lu, Chenming; Pop, Ana; Struys, Eduard A; Jansen, Erwin E W; Salomons, Gajja S; David, Muriel D; Quivoron, Cyril; Penard-Lacronique, Virginie; Regan, Karen S; Liu, Wei; Dang, Lenny; Yang, Hua; Silverman, Lee; Agresta, Samuel; Dorsch, Marion; Biller, Scott; Yen, Katharine; Cang, Yong; Su, Shin-San Michael; Jin, Shengfang

    2016-11-01

    D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus. Idh2R140Q mice displayed significantly elevated 2HG levels and recapitulated multiple defects seen in patients. AGI-026, a potent, selective inhibitor of the human IDH2R140Q-mutant enzyme, suppressed 2HG production, rescued cardiomyopathy, and provided a survival benefit in Idh2R140Q mice; treatment withdrawal resulted in deterioration of cardiac function. We observed differential expression of multiple genes and metabolites that are associated with cardiomyopathy, which were largely reversed by AGI-026. These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II.

  6. Evolutionary institutionalism.

    Science.gov (United States)

    Fürstenberg, Dr Kai

    Institutions are hard to define and hard to study. Long prominent in political science have been two theories: Rational Choice Institutionalism (RCI) and Historical Institutionalism (HI). Arising from the life sciences is now a third: Evolutionary Institutionalism (EI). Comparative strengths and weaknesses of these three theories warrant review, and the value-to-be-added by expanding the third beyond Darwinian evolutionary theory deserves consideration. Should evolutionary institutionalism expand to accommodate new understanding in ecology, such as might apply to the emergence of stability, and in genetics, such as might apply to political behavior? Core arguments are reviewed for each theory with more detailed exposition of the third, EI. Particular attention is paid to EI's gene-institution analogy; to variation, selection, and retention of institutional traits; to endogeneity and exogeneity; to agency and structure; and to ecosystem effects, institutional stability, and empirical limitations in behavioral genetics. RCI, HI, and EI are distinct but complementary. Institutional change, while amenable to rational-choice analysis and, retrospectively, to criticaljuncture and path-dependency analysis, is also, and importantly, ecological. Stability, like change, is an emergent property of institutions, which tend to stabilize after change in a manner analogous to allopatric speciation. EI is more than metaphorically biological in that institutional behaviors are driven by human behaviors whose evolution long preceded the appearance of institutions themselves.

  7. Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's

    Directory of Open Access Journals (Sweden)

    Houchard Kimberly R

    2005-02-01

    Full Text Available Abstract Background Excessive sequential stereotypy of behavioral patterns (sequential super-stereotypy in Tourette's syndrome and obsessive compulsive disorder (OCD is thought to involve dysfunction in nigrostriatal dopamine systems. In sequential super-stereotypy, patients become trapped in overly rigid sequential patterns of action, language, or thought. Some instinctive behavioral patterns of animals, such as the syntactic grooming chain pattern of rodents, have sufficiently complex and stereotyped serial structure to detect potential production of overly-rigid sequential patterns. A syntactic grooming chain is a fixed action pattern that serially links up to 25 grooming movements into 4 predictable phases that follow 1 syntactic rule. New mutant mouse models allow gene-based manipulation of brain function relevant to sequential patterns, but no current animal model of spontaneous OCD-like behaviors has so far been reported to exhibit sequential super-stereotypy in the sense of a whole complex serial pattern that becomes stronger and excessively rigid. Here we used a hyper-dopaminergic mutant mouse to examine whether an OCD-like behavioral sequence in animals shows sequential super-stereotypy. Knockdown mutation of the dopamine transporter gene (DAT causes extracellular dopamine levels in the neostriatum of these adult mutant mice to rise to 170% of wild-type control levels. Results We found that the serial pattern of this instinctive behavioral sequence becomes strengthened as an entire entity in hyper-dopaminergic mutants, and more resistant to interruption. Hyper-dopaminergic mutant mice have stronger and more rigid syntactic grooming chain patterns than wild-type control mice. Mutants showed sequential super-stereotypy in the sense of having more stereotyped and predictable syntactic grooming sequences, and were also more likely to resist disruption of the pattern en route, by returning after a disruption to complete the pattern from the

  8. Evolutionary relationships of Aurora kinases: Implications for model organism studies and the development of anti-cancer drugs

    Directory of Open Access Journals (Sweden)

    Patrick Denis R

    2004-10-01

    Full Text Available Abstract Background As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family. Results Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A. Conclusions In

  9. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

    Science.gov (United States)

    McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

  10. Comparing multi-objective non-evolutionary NLPQL and evolutionary genetic algorithm optimization of a DI diesel engine: DoE estimation and creating surrogate model

    International Nuclear Information System (INIS)

    Navid, Ali; Khalilarya, Shahram; Taghavifar, Hadi

    2016-01-01

    Highlights: • NLPQL algorithm with Latin hypercube and multi-objective GA were applied on engine. • NLPQL converge to the best solution at RunID41, MOGA introduces at RunID84. • Deeper, more encircled design gives the lowest NOx, greater radius and deeper bowl the highest IMEP. • The maximum IMEP and minimum ISFC obtained with NLPQL, the lowest NOx with MOGA. - Abstract: This study is concerned with the application of two major kinds of optimization algorithms on the baseline diesel engine in the class of evolutionary and non-evolutionary algorithms. The multi-objective genetic algorithm and non-linear programming by quadratic Lagrangian (NLPQL) method have completely different functions in optimizing and finding the global optimal design. The design variables are injection angle, half spray cone angle, inner distance of the bowl wall, and the bowl radius, while the objectives include NOx emission, spray droplet diameter, indicated mean effective pressure (IMEP), and indicated specific fuel consumption (ISFC). The restrictions were set on the objectives to distinguish between feasible designs and infeasible designs to sort those cases that cannot fulfill the demands of diesel engine designers and emission control measures. It is found that a design with deeper bowl and more encircled shape (higher swirl motion) is more suitable for NO_x emission control, whereas designs with a bigger bowl radius, and closer inner wall distance of the bowl (Di) may lead to higher engine efficiency indices. Moreover, it was revealed that the NLPQL could rapidly search for the best design at Run ID 41 compared to genetic algorithm, which is able to find the global optima at last runs (ID 84). Both techniques introduce almost the same geometrical shape of the combustion chamber with a negligible contrast in the injection system.

  11. Evolutionary mysteries in meiosis

    NARCIS (Netherlands)

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E.; Wijnker, Erik; Haag, Christoph R.

    2016-01-01

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these

  12. Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition

    Science.gov (United States)

    Gunn, Rhian K.; Huentelman, Matthew J.; Brown, Richard E.

    2011-01-01

    Semaphorin 5A (Sema5A) expression is reduced in the brain of individuals with autism, thus mice with reduced Sema5A levels may serve as a model of this neurodevelopmental disorder. We tested male and female Sema5a knockout mice (B6.129P2SEMA5A/J) and C57BL/6J controls for emotionality, visual ability, prepulse inhibition, motor learning and cognition. Overall, there were only two genotype differences in emotionality: Sema5a mutant mice had more stretch-attend postures in the elevated plus-maze and more defecations in the open field. All mice could see, but Sema5a mice had better visual ability than C57BL/6J mice. There were no genotype differences in sensory-motor gating. Sema5a mice showed higher levels of activity in the elevated plus-maze and light/dark transition box, and there were sex by genotype differences in the Rotarod, suggesting a sex difference in balance and coordination differentially affected by Sema5a. There were no genotype effects on cognition: Sema5a mice did not differ from C57BL/6J in the Morris water maze, set-shifting or cued and contextual fear conditioning. In the social recognition test, all mice preferred social stimuli, but there was no preference for social novelty, thus the Sema5A mice do not have a deficit in social behavior. Overall, there were a number of sex differences, with females showing greater activity and males performing better in tests of spatial learning and memory, but no deficits in the behavior of Sema5A mice. We conclude that the Sema5a mice do not meet the behavioral criteria for a mouse model of autism. PMID:21777623

  13. Soft tissue freezing process. Identification of the dual-phase lag model parameters using the evolutionary algorithm

    Science.gov (United States)

    Mochnacki, Bohdan; Majchrzak, Ewa; Paruch, Marek

    2018-01-01

    In the paper the soft tissue freezing process is considered. The tissue sub-domain is subjected to the action of cylindrical cryoprobe. Thermal processes proceeding in the domain considered are described using the dual-phase lag equation (DPLE) supplemented by the appropriate boundary and initial conditions. DPLE results from the generalization of the Fourier law in which two lag times are introduced (relaxation and thermalization times). The aim of research is the identification of these parameters on the basis of measured cooling curves at the set of points selected from the tissue domain. To solve the problem the evolutionary algorithms are used. The paper contains the mathematical model of the tissue freezing process, the very short information concerning the numerical solution of the basic problem, the description of the inverse problem solution and the results of computations.

  14. Genetic hotels for the standard genetic code: evolutionary analysis based upon novel three-dimensional algebraic models.

    Science.gov (United States)

    José, Marco V; Morgado, Eberto R; Govezensky, Tzipe

    2011-07-01

    Herein, we rigorously develop novel 3-dimensional algebraic models called Genetic Hotels of the Standard Genetic Code (SGC). We start by considering the primeval RNA genetic code which consists of the 16 codons of type RNY (purine-any base-pyrimidine). Using simple algebraic operations, we show how the RNA code could have evolved toward the current SGC via two different intermediate evolutionary stages called Extended RNA code type I and II. By rotations or translations of the subset RNY, we arrive at the SGC via the former (type I) or via the latter (type II), respectively. Biologically, the Extended RNA code type I, consists of all codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The Extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. Since the dimensions of remarkable subsets of the Genetic Hotels are not necessarily integer numbers, we also introduce the concept of algebraic fractal dimension. A general decoding function which maps each codon to its corresponding amino acid or the stop signals is also derived. The Phenotypic Hotel of amino acids is also illustrated. The proposed evolutionary paths are discussed in terms of the existing theories of the evolution of the SGC. The adoption of 3-dimensional models of the Genetic and Phenotypic Hotels will facilitate the understanding of the biological properties of the SGC.

  15. Mitochondrial glutamate carriers from Drosophila melanogaster: biochemical, evolutionary and modeling studies.

    Science.gov (United States)

    Lunetti, Paola; Cappello, Anna Rita; Marsano, René Massimiliano; Pierri, Ciro Leonardo; Carrisi, Chiara; Martello, Emanuela; Caggese, Corrado; Dolce, Vincenza; Capobianco, Loredana

    2013-10-01

    The mitochondrial carriers are members of a family of transport proteins that mediate solute transport across the inner mitochondrial membrane. Two isoforms of the glutamate carriers, GC1 and GC2 (encoded by the SLC25A22 and SLC25A18 genes, respectively), have been identified in humans. Two independent mutations in SLC25A22 are associated with severe epileptic encephalopathy. In the present study we show that two genes (CG18347 and CG12201) phylogenetically related to the human GC encoding genes are present in the D. melanogaster genome. We have functionally characterized the proteins encoded by CG18347 and CG12201, designated as DmGC1p and DmGC2p respectively, by overexpression in Escherichia coli and reconstitution into liposomes. Their transport properties demonstrate that DmGC1p and DmGC2p both catalyze the transport of glutamate across the inner mitochondrial membrane. Computational approaches have been used in order to highlight residues of DmGC1p and DmGC2p involved in substrate binding. Furthermore, gene expression analysis during development and in various adult tissues reveals that CG18347 is ubiquitously expressed in all examined D. melanogaster tissues, while the expression of CG12201 is strongly testis-biased. Finally, we identified mitochondrial glutamate carrier orthologs in 49 eukaryotic species in order to attempt the reconstruction of the evolutionary history of the glutamate carrier function. Comparison of the exon/intron structure and other key features of the analyzed orthologs suggests that eukaryotic glutamate carrier genes descend from an intron-rich ancestral gene already present in the common ancestor of lineages that diverged as early as bilateria and radiata. © 2013.

  16. Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS

    Science.gov (United States)

    Estes, Patricia S.; Boehringer, Ashley; Zwick, Rebecca; Tang, Jonathan E.; Grigsby, Brianna; Zarnescu, Daniela C.

    2011-01-01

    The RNA-binding protein TDP-43 has been linked to amyotrophic lateral sclerosis (ALS) both as a causative locus and as a marker of pathology. With several missense mutations being identified within TDP-43, efforts have been directed towards generating animal models of ALS in mouse, zebrafish, Drosophila and worms. Previous loss of function and overexpression studies have shown that alterations in TDP-43 dosage recapitulate hallmark features of ALS pathology, including neuronal loss and locomotor dysfunction. Here we report a direct in vivo comparison between wild-type and A315T mutant TDP-43 overexpression in Drosophila neurons. We found that when expressed at comparable levels, wild-type TDP-43 exerts more severe effects on neuromuscular junction architecture, viability and motor neuron loss compared with the A315T allele. A subset of these differences can be compensated by higher levels of A315T expression, indicating a direct correlation between dosage and neurotoxic phenotypes. Interestingly, larval locomotion is the sole parameter that is more affected by the A315T allele than wild-type TDP-43. RNA interference and genetic interaction experiments indicate that TDP-43 overexpression mimics a loss-of-function phenotype and suggest a dominant-negative effect. Furthermore, we show that neuronal apoptosis does not require the cytoplasmic localization of TDP-43 and that its neurotoxicity is modulated by the proteasome, the HSP70 chaperone and the apoptosis pathway. Taken together, our findings provide novel insights into the phenotypic consequences of the A315T TDP-43 missense mutation and suggest that studies of individual mutations are critical for elucidating the molecular mechanisms of ALS and related neurodegenerative disorders. PMID:21441568

  17. Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach

    Directory of Open Access Journals (Sweden)

    Fantucci Piercarlo

    2010-03-01

    Full Text Available Abstract Background GPR17 is a hybrid G-protein-coupled receptor (GPCR activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes (cysteinyl-LTs, and involved in brain damage and repair. Its exploitment as a target for novel neuro-reparative strategies depends on the elucidation of the molecular determinants driving binding of purinergic and leukotrienic ligands. Here, we applied docking and molecular dynamics simulations (MD to analyse the binding and the forced unbinding of two GPR17 ligands (the endogenous purinergic agonist UDP and the leukotriene receptor antagonist pranlukast from both the wild-type (WT receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I to Ile. Results MD suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and extracellular loop (EL 2. The driving interaction involves R255 and the UDP phosphate moiety. To support this hypothesis, steered MD experiments showed that the energy required to unbind UDP is higher for the WT receptor than for R255I. Three potential binding sites for pranlukast where instead found and analysed. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the WT receptor and the R255I receptor were found for the unbinding of pranlukast. Conclusions These data thus suggest that, in contrast to which has been hypothesized for nucleotides, the lack of the R255 residue doesn't affect the binding of pranlukast a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17.

  18. An Evolutionary, Agent-Based Model to Aid in Computer Intrusion Detection and Prevention

    National Research Council Canada - National Science Library

    Shargel, Ben; Bonabeau, Eric; Budynek, Julien; Gaudiano, Paolo

    2005-01-01

    We have developed a realistic agent-based simulation model of hacker behavior. In the model, hacker scripts are generated using a simple but powerful hacker grammar that has the potential to cover all possible hacker scripts...

  19. Past, present and future distributions of an Iberian Endemic, Lepus granatensis: ecological and evolutionary clues from species distribution models.

    Directory of Open Access Journals (Sweden)

    Pelayo Acevedo

    Full Text Available The application of species distribution models (SDMs in ecology and conservation biology is increasing and assuming an important role, mainly because they can be used to hindcast past and predict current and future species distributions. However, the accuracy of SDMs depends on the quality of the data and on appropriate theoretical frameworks. In this study, comprehensive data on the current distribution of the Iberian hare (Lepus granatensis were used to i determine the species' ecogeographical constraints, ii hindcast a climatic model for the last glacial maximum (LGM, relating it to inferences derived from molecular studies, and iii calibrate a model to assess the species future distribution trends (up to 2080. Our results showed that the climatic factor (in its pure effect and when it is combined with the land-cover factor is the most important descriptor of the current distribution of the Iberian hare. In addition, the model's output was a reliable index of the local probability of species occurrence, which is a valuable tool to guide species management decisions and conservation planning. Climatic potential obtained for the LGM was combined with molecular data and the results suggest that several glacial refugia may have existed for the species within the major Iberian refugium. Finally, a high probability of occurrence of the Iberian hare in the current species range and a northward expansion were predicted for future. Given its current environmental envelope and evolutionary history, we discuss the macroecology of the Iberian hare and its sensitivity to climate change.

  20. Past, present and future distributions of an Iberian Endemic, Lepus granatensis: ecological and evolutionary clues from species distribution models.

    Science.gov (United States)

    Acevedo, Pelayo; Melo-Ferreira, José; Real, Raimundo; Alves, Paulo Célio

    2012-01-01

    The application of species distribution models (SDMs) in ecology and conservation biology is increasing and assuming an important role, mainly because they can be used to hindcast past and predict current and future species distributions. However, the accuracy of SDMs depends on the quality of the data and on appropriate theoretical frameworks. In this study, comprehensive data on the current distribution of the Iberian hare (Lepus granatensis) were used to i) determine the species' ecogeographical constraints, ii) hindcast a climatic model for the last glacial maximum (LGM), relating it to inferences derived from molecular studies, and iii) calibrate a model to assess the species future distribution trends (up to 2080). Our results showed that the climatic factor (in its pure effect and when it is combined with the land-cover factor) is the most important descriptor of the current distribution of the Iberian hare. In addition, the model's output was a reliable index of the local probability of species occurrence, which is a valuable tool to guide species management decisions and conservation planning. Climatic potential obtained for the LGM was combined with molecular data and the results suggest that several glacial refugia may have existed for the species within the major Iberian refugium. Finally, a high probability of occurrence of the Iberian hare in the current species range and a northward expansion were predicted for future. Given its current environmental envelope and evolutionary history, we discuss the macroecology of the Iberian hare and its sensitivity to climate change.

  1. Bi-directional evolutionary structural optimization for strut-and-tie modelling of three-dimensional structural concrete

    Science.gov (United States)

    Shobeiri, Vahid; Ahmadi-Nedushan, Behrouz

    2017-12-01

    This article presents a method for the automatic generation of optimal strut-and-tie models in reinforced concrete structures using a bi-directional evolutionary structural optimization method. The methodology presented is developed for compliance minimization relying on the Abaqus finite element software package. The proposed approach deals with the generation of truss-like designs in a three-dimensional environment, addressing the design of corbels and joints as well as bridge piers and pile caps. Several three-dimensional examples are provided to show the capabilities of the proposed framework in finding optimal strut-and-tie models in reinforced concrete structures and verifying its efficiency to cope with torsional actions. Several issues relating to the use of the topology optimization for strut-and-tie modelling of structural concrete, such as chequerboard patterns, mesh-dependency and multiple load cases, are studied. In the last example, a design procedure for detailing and dimensioning of the strut-and-tie models is given according to the American Concrete Institute (ACI) 318-08 provisions.

  2. Mutant prevention concentration, pharmacokinetic-pharmacodynamic integration, and modeling of enrofloxacin data established in diseased buffalo calves.

    Science.gov (United States)

    Ramalingam, B; Sidhu, P K; Kaur, G; Venkatachalam, D; Rampal, S

    2015-12-01

    The pharmacokinetic-pharmacodynamic (PK/PD) modeling of enrofloxacin data using mutant prevention concentration (MPC) of enrofloxacin was conducted in febrile buffalo calves to optimize dosage regimen and to prevent the emergence of antimicrobial resistance. The serum peak concentration (Cmax ), terminal half-life (t1/2 K10) , apparent volume of distribution (Vd(area) /F), and mean residence time (MRT) of enrofloxacin were 1.40 ± 0.27 μg/mL, 7.96 ± 0.86 h, 7.74 ± 1.26 L/kg, and 11.57 ± 1.01 h, respectively, following drug administration at dosage 12 mg/kg by intramuscular route. The minimum inhibitory concentration (MIC), minimum bactericidal concentration, and MPC of enrofloxacin against Pasteurella multocida were 0.055, 0.060, and 1.45 μg/mL, respectively. Modeling of ex vivo growth inhibition data to the sigmoid Emax equation provided AUC24 h /MIC values to produce effects of bacteriostatic (33 h), bactericidal (39 h), and bacterial eradication (41 h). The estimated daily dosage of enrofloxacin in febrile buffalo calves was 3.5 and 8.4 mg/kg against P. multocida/pathogens having MIC90 ≤0.125 and 0.30 μg/mL, respectively, based on the determined AUC24 h /MIC values by modeling PK/PD data. The lipopolysaccharide-induced fever had no direct effect on the antibacterial activity of the enrofloxacin and alterations in PK of the drug, and its metabolite will be beneficial for its use to treat infectious diseases caused by sensitive pathogens in buffalo species. In addition, in vitro MPC data in conjunction with in vivo PK data indicated that clinically it would be easier to eradicate less susceptible strains of P. multocida in diseased calves. © 2015 John Wiley & Sons Ltd.

  3. The search for evolutionary developmental origins of aging in zebrafish: a novel intersection of developmental and senescence biology in the zebrafish model system.

    Science.gov (United States)

    Kishi, Shuji

    2011-09-01

    Senescence may be considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena during the process of aging. We investigated whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We conducted experiments to isolate zebrafish mutants expressing an apparent senescence phenotype during embryogenesis (embryonic senescence). Some of the genes we thereby identified had already been associated with cellular senescence and chronological aging in other organisms, but many had not yet been linked to these processes. Complete loss-of-function of developmentally essential genes induce embryonic (or larval) lethality, whereas it seems like their partial loss-of-function (i.e., decrease-of-function by heterozygote or hypomorphic mutations) still remains sufficient to go through the early developmental process because of its adaptive plasticity or rather heterozygote advantage. However, in some cases, such partial loss-of-function of genes compromise normal homeostasis due to haploinsufficiency later in adult life having many environmental stress challenges. By contrast, any heterozygote-advantageous genes might gain a certain benefit(s) (much more fitness) by such partial loss-of-function later in life. Physiological senescence may evolutionarily arise from both genetic and epigenetic drifts as well as from losing adaptive developmental plasticity in face of stress signals from the external environment that interacts with functions of multiple genes rather than effects of only a single gene mutation or defect. Previously uncharacterized developmental genes may thus mediate the aging process and play a pivotal role in senescence. Moreover, unexpected senescence-related genes might also be involved in the early developmental process and

  4. An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing.

    Science.gov (United States)

    Wu, Zujian; Pang, Wei; Coghill, George M

    2015-01-01

    Both qualitative and quantitative model learning frameworks for biochemical systems have been studied in computational systems biology. In this research, after introducing two forms of pre-defined component patterns to represent biochemical models, we propose an integrative qualitative and quantitative modelling framework for inferring biochemical systems. In the proposed framework, interactions between reactants in the candidate models for a target biochemical system are evolved and eventually identified by the application of a qualitative model learning approach with an evolution strategy. Kinetic rates of the models generated from qualitative model learning are then further optimised by employing a quantitative approach with simulated annealing. Experimental results indicate that our proposed integrative framework is feasible to learn the relationships between biochemical reactants qualitatively and to make the model replicate the behaviours of the target system by optimising the kinetic rates quantitatively. Moreover, potential reactants of a target biochemical system can be discovered by hypothesising complex reactants in the synthetic models. Based on the biochemical models learned from the proposed framework, biologists can further perform experimental study in wet laboratory. In this way, natural biochemical systems can be better understood.

  5. Beryllium abundances along the evolutionary sequence of the open cluster IC 4651 - A new test for hydrodynamical stellar models

    Science.gov (United States)

    Smiljanic, R.; Pasquini, L.; Charbonnel, C.; Lagarde, N.

    2010-02-01

    Context. Previous analyses of lithium abundances in main sequence and red giant stars have revealed the action of mixing mechanisms other than convection in stellar interiors. Beryllium abundances in stars with Li abundance determinations can offer valuable complementary information on the nature of these mechanisms. Aims: Our aim is to derive Be abundances along the whole evolutionary sequence of an open cluster. We focus on the well-studied open cluster IC 4651. These Be abundances are used with previously determined Li abundances, in the same sample stars, to investigate the mixing mechanisms in a range of stellar masses and evolutionary stages. Methods: Atmospheric parameters were adopted from a previous abundance analysis by the same authors. New Be abundances have been determined from high-resolution, high signal-to-noise UVES spectra using spectrum synthesis and model atmospheres. The careful synthetic modeling of the Be lines region is used to calculate reliable abundances in rapidly rotating stars. The observed behavior of Be and Li is compared to theoretical predictions from stellar models including rotation-induced mixing, internal gravity waves, atomic diffusion, and thermohaline mixing. Results: Beryllium is detected in all the main sequence and turn-off sample stars, both slow- and fast-rotating stars, including the Li-dip stars, but is not detected in the red giants. Confirming previous results, we find that the Li dip is also a Be dip, although the depletion of Be is more modest than for Li in the corresponding effective temperature range. For post-main-sequence stars, the Be dilution starts earlier within the Hertzsprung gap than expected from classical predictions, as does the Li dilution. A clear dispersion in the Be abundances is also observed. Theoretical stellar models including the hydrodynamical transport processes mentioned above are able to reproduce all the observed features well. These results show a good theoretical understanding of the

  6. Behavioural effects of high fat diet in a mutant mouse model for the schizophrenia risk gene neuregulin 1

    DEFF Research Database (Denmark)

    Holm-hansen, S.; Low, J. K.; Zieba, J.

    2016-01-01

    on the behavioural phenotype of test mice and attenuated particular cognitive deficits of Nrg1 mutant females. This topic requires further investigations thereby also considering other dietary factors of relevance for schizophrenia as well as interactive effects of diet with medication and sex....

  7. Evolutionary considerations on complex emotions and music-induced emotions. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Gingras, Bruno; Marin, Manuela M.

    2015-06-01

    Recent efforts to uncover the neural underpinnings of emotional experiences have provided a foundation for novel neurophysiological theories of emotions, adding to the existing body of psychophysiological, motivational, and evolutionary theories. Besides explicitly modeling human-specific emotions and considering the interactions between emotions and language, Koelsch et al.'s original contribution to this challenging endeavor is to identify four brain areas as distinct "affect systems" which differ in terms of emotional qualia and evolutionary pathways [1]. Here, we comment on some features of this promising Quartet Theory of Emotions, focusing particularly on evolutionary and biological aspects related to the four affect systems and their relation to prevailing emotion theories, as well as on the role of music-induced emotions.

  8. Barriers to knowledge spillovers and regional convergence in an evolutionary model

    NARCIS (Netherlands)

    Caniëls, M.C.J.; Verspagen, B.

    2001-01-01

    This paper will present a multi-region/multi-country model in which inter-regional knowledge spillovers determine the growth of regions. Key parameters in the model are the learning capability of a region and the rate of knowledge generation (R&D). The intensity of spillovers depends on geographical

  9. A coupled classification - evolutionary optimization model for contamination event detection in water distribution systems.

    Science.gov (United States)

    Oliker, Nurit; Ostfeld, Avi

    2014-03-15

    This study describes a decision support system, alerts for contamination events in water distribution systems. The developed model comprises a weighted support vector machine (SVM) for the detection of outliers, and a following sequence analysis for the classification of contamination events. The contribution of this study is an improvement of contamination events detection ability and a multi-dimensional analysis of the data, differing from the parallel one-dimensional analysis conducted so far. The multivariate analysis examines the relationships between water quality parameters and detects changes in their mutual patterns. The weights of the SVM model accomplish two goals: blurring the difference between sizes of the two classes' data sets (as there are much more normal/regular than event time measurements), and adhering the time factor attribute by a time decay coefficient, ascribing higher importance to recent observations when classifying a time step measurement. All model parameters were determined by data driven optimization so the calibration of the model was completely autonomic. The model was trained and tested on a real water distribution system (WDS) data set with randomly simulated events superimposed on the original measurements. The model is prominent in its ability to detect events that were only partly expressed in the data (i.e., affecting only some of the measured parameters). The model showed high accuracy and better detection ability as compared to previous modeling attempts of contamination event detection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Automated evolutionary restructuring of workflows to minimise errors via stochastic model checking

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Hansen, Zaza Nadja Lee; Jacobsen, Peter

    2014-01-01

    This paper presents a framework for the automated restructuring of workflows that allows one to minimise the impact of errors on a production workflow. The framework allows for the modelling of workflows by means of a formalised subset of the Business Process Modelling and Notation (BPMN) language...

  11. Restructuring of workflows to minimise errors via stochastic model checking: An automated evolutionary approach

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Hansen, Zaza Nadja Lee

    2016-01-01

    This article presents a framework for the automated restructuring of stochastic workflows to reduce the impact of faults. The framework allows for the modelling of workflows by means of a formalised subset of the BPMN workflow language. We extend this modelling formalism to describe faults...

  12. Evolutionary Explanations of Eating Disorders

    Directory of Open Access Journals (Sweden)

    Igor Kardum

    2008-12-01

    Full Text Available This article reviews several most important evolutionary mechanisms that underlie eating disorders. The first part clarifies evolutionary foundations of mental disorders and various mechanisms leading to their development. In the second part selective pressures and evolved adaptations causing contemporary epidemic of obesity as well as differences in dietary regimes and life-style between modern humans and their ancestors are described. Concerning eating disorders, a number of current evolutionary explanations of anorexia nervosa are presented together with their main weaknesses. Evolutionary explanations of eating disorders based on the reproductive suppression hypothesis and its variants derived from kin selection theory and the model of parental manipulation were elaborated. The sexual competition hypothesis of eating disorder, adapted to flee famine hypothesis as well as explanation based on the concept of social attention holding power and the need to belonging were also explained. The importance of evolutionary theory in modern conceptualization and research of eating disorders is emphasized.

  13. Why do we like to stay with our friends? Modelling the evolutionary dynamics of interpersonal commitment

    NARCIS (Netherlands)

    Back, I.; Flache, A.; Takahashi, S; Scallach, D; Rouchier, J

    2007-01-01

    Why are people inclined to build friendships and maintain durable, nonreproductive relationships? Previous computational modeling work on the evolution of commitment in repeated exchange showed that being largely unconditionally cooperative in committed relationships is more viable than conditional

  14. Evolutionary disarmament in interspecific competition.

    Science.gov (United States)

    Kisdi, E; Geritz, S A

    2001-12-22

    Competitive asymmetry, which is the advantage of having a larger body or stronger weaponry than a contestant, drives spectacular evolutionary arms races in intraspecific competition. Similar asymmetries are well documented in interspecific competition, yet they seldom lead to exaggerated traits. Here we demonstrate that two species with substantially different size may undergo parallel coevolution towards a smaller size under the same ecological conditions where a single species would exhibit an evolutionary arms race. We show that disarmament occurs for a wide range of parameters in an ecologically explicit model of competition for a single shared resource; disarmament also occurs in a simple Lotka-Volterra competition model. A key property of both models is the interplay between evolutionary dynamics and population density. The mechanism does not rely on very specific features of the model. Thus, evolutionary disarmament may be widespread and may help to explain the lack of interspecific arms races.

  15. Improvements in seismic event locations in a deep western U.S. coal mine using tomographic velocity models and an evolutionary search algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Adam Lurka; Peter Swanson [Central Mining Institute, Katowice (Poland)

    2009-09-15

    Methods of improving seismic event locations were investigated as part of a research study aimed at reducing ground control safety hazards. Seismic event waveforms collected with a 23-station three-dimensional sensor array during longwall coal mining provide the data set used in the analyses. A spatially variable seismic velocity model is constructed using seismic event sources in a passive tomographic method. The resulting three-dimensional velocity model is used to relocate seismic event positions. An evolutionary optimization algorithm is implemented and used in both the velocity model development and in seeking improved event location solutions. Results obtained using the different velocity models are compared. The combination of the tomographic velocity model development and evolutionary search algorithm provides improvement to the event locations. 13 refs., 5 figs., 4 tabs.

  16. Application of an Evolutionary Algorithm for Parameter Optimization in a Gully Erosion Model

    Energy Technology Data Exchange (ETDEWEB)

    Rengers, Francis; Lunacek, Monte; Tucker, Gregory

    2016-06-01

    Herein we demonstrate how to use model optimization to determine a set of best-fit parameters for a landform model simulating gully incision and headcut retreat. To achieve this result we employed the Covariance Matrix Adaptation Evolution Strategy (CMA-ES), an iterative process in which samples are created based on a distribution of parameter values that evolve over time to better fit an objective function. CMA-ES efficiently finds optimal parameters, even with high-dimensional objective functions that are non-convex, multimodal, and non-separable. We ran model instances in parallel on a high-performance cluster, and from hundreds of model runs we obtained the best parameter choices. This method is far superior to brute-force search algorithms, and has great potential for many applications in earth science modeling. We found that parameters representing boundary conditions tended to converge toward an optimal single value, whereas parameters controlling geomorphic processes are defined by a range of optimal values.

  17. Um modelo evolucionário Norte-Sul A North-South evolutionary model

    Directory of Open Access Journals (Sweden)

    André Luiz Fernandes

    2007-12-01

    Full Text Available This work expands the classical Nelson and Winter model of Schumpeterian competition by including two sectors and a North-South dynamics, with a view to analyzing how different institutions and technological regimes affect the processes of convergence and divergence in the international economy. The results suggest that convergence may emerge out of the efforts for imitation in the South when the technological regime is cumulative. But when the regime is science-based, imitation is not enough for a successful catching-up. In this case convergence requires the South to invest in innovation as well. The work also analyses the robustness of the model results using Montecarlo techniques.

  18. An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis.

    Science.gov (United States)

    Peters, Brian M; Luna-Tapia, Arturo; Tournu, Hélène; Rybak, Jeffrey M; Rogers, P David; Palmer, Glen E

    2017-06-01

    We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21 Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro , it does not seem to affect azole susceptibility in vivo . Copyright © 2017 American Society for Microbiology.

  19. The Social Life of Greylag Geese : Patterns, Mechanisms and Evolutionary Function in an Avian Model System

    NARCIS (Netherlands)

    Scheiber, Isabella; Weiß, Brigitte M.; Hemetsberger, Josef; Kotrschal, Kurt

    The flock of greylag geese established by Konrad Lorenz in Austria in 1973 has become an influential model animal system and one of the few worldwide with complete life-history data spanning several decades. Based on the unique records of nearly 1000 free-living greylag geese, this is a synthesis of

  20. Designing a Pedagogical Model for Web Engineering Education: An Evolutionary Perspective

    Science.gov (United States)

    Hadjerrouit, Said

    2005-01-01

    In contrast to software engineering, which relies on relatively well established development approaches, there is a lack of a proven methodology that guides Web engineers in building reliable and effective Web-based systems. Currently, Web engineering lacks process models, architectures, suitable techniques and methods, quality assurance, and a…

  1. How can we model selectively neutral density dependence in evolutionary games.

    Science.gov (United States)

    Argasinski, Krzysztof; Kozłowski, Jan

    2008-03-01

    The problem of density dependence appears in all approaches to the modelling of population dynamics. It is pertinent to classic models (i.e., Lotka-Volterra's), and also population genetics and game theoretical models related to the replicator dynamics. There is no density dependence in the classic formulation of replicator dynamics, which means that population size may grow to infinity. Therefore the question arises: How is unlimited population growth suppressed in frequency-dependent models? Two categories of solutions can be found in the literature. In the first, replicator dynamics is independent of background fitness. In the second type of solution, a multiplicative suppression coefficient is used, as in a logistic equation. Both approaches have disadvantages. The first one is incompatible with the methods of life history theory and basic probabilistic intuitions. The logistic type of suppression of per capita growth rate stops trajectories of selection when population size reaches the maximal value (carrying capacity); hence this method does not satisfy selective neutrality. To overcome these difficulties, we must explicitly consider turn-over of individuals dependent on mortality rate. This new approach leads to two interesting predictions. First, the equilibrium value of population size is lower than carrying capacity and depends on the mortality rate. Second, although the phase portrait of selection trajectories is the same as in density-independent replicator dynamics, pace of selection slows down when population size approaches equilibrium, and then remains constant and dependent on the rate of turn-over of individuals.

  2. Why the CLASH model is an unconvincing evolutionary theory of crime.

    Science.gov (United States)

    Boutwell, Brian B; Winegard, Bo

    2017-01-01

    The CLASH model is not convincing for two reasons. First, it ignores prior research proposing very similar ideas in a more compelling fashion. Second, it dismisses the role of genetic factors in shaping criminal propensities across population groups, opting for a facultative view of life history evolution that does not seem to square with current evidence.

  3. Evolutionary stellar population synthesis with MILES : I. The base models and a new line index system

    NARCIS (Netherlands)

    Vazdekis, A.; Sanchez-Blazquez, P.; Falcon-Barroso, J.; Cenarro, A. J.; Beasley, M. A.; Cardiel, N.; Gorgas, J.; Peletier, R. F.

    2010-01-01

    We present synthetic spectral energy distributions (SEDs) for single-age, single-metallicity stellar populations (SSPs) covering the full optical spectral range at moderately high resolution [full width at half-maximum (FWHM) = 2.3Å]. These SEDs constitute our base models, as they combine

  4. Different phylogenomic approaches to resolve the evolutionary relationships among model fish species.

    Science.gov (United States)

    Negrisolo, Enrico; Kuhl, Heiner; Forcato, Claudio; Vitulo, Nicola; Reinhardt, Richard; Patarnello, Tomaso; Bargelloni, Luca

    2010-12-01

    Comparative genomics holds the promise to magnify the information obtained from individual genome sequencing projects, revealing common features conserved across genomes and identifying lineage-specific characteristics. To implement such a comparative approach, a robust phylogenetic framework is required to accurately reconstruct evolution at the genome level. Among vertebrate taxa, teleosts represent the second best characterized group, with high-quality draft genome sequences for five model species (Danio rerio, Gasterosteus aculeatus, Oryzias latipes, Takifugu rubripes, and Tetraodon nigroviridis), and several others are in the finishing lane. However, the relationships among the acanthomorph teleost model fishes remain an unresolved taxonomic issue. Here, a genomic region spanning over 1.2 million base pairs was sequenced in the teleost fish Dicentrarchus labrax. Together with genomic data available for the above fish models, the new sequence was used to identify unique orthologous genomic regions shared across all target taxa. Different strategies were applied to produce robust multiple gene and genomic alignments spanning from 11,802 to 186,474 amino acid/nucleotide positions. Ten data sets were analyzed according to Bayesian inference, maximum likelihood, maximum parsimony, and neighbor joining methods. Extensive analyses were performed to explore the influence of several factors (e.g., alignment methodology, substitution model, data set partitions, and long-branch attraction) on the tree topology. Although a general consensus was observed for a closer relationship between G. aculeatus (Gasterosteidae) and Di. labrax (Moronidae) with the atherinomorph O. latipes (Beloniformes) sister taxon of this clade, with the tetraodontiform group Ta. rubripes and Te. nigroviridis (Tetraodontiformes) representing a more distantly related taxon among acanthomorph model fish species, conflicting results were obtained between data sets and methods, especially with respect

  5. Emergence of competition and cooperation in an evolutionary resource war model

    Science.gov (United States)

    Lamantia, Fabio

    2018-05-01

    In this paper we introduce a simple punishment scheme in the 'great fish war' model with many players. An imitative process regulates how a coalition of cooperators is dynamically updated over time. An intuitive effect of adding sanctions is that they could enlarge the possible sustainable coalitions. However, the evolution toward full cooperation can be sustained by a punishment scheme provided that a critical mass of agents enforces cooperation at the beginning of the game. Moreover, we show the presence of thresholds in sanctions or in the cost for punishing such that if these thresholds are trespassed then dramatic reductions in the resource level and in the agents' welfare may occur as a consequence of free riding effects. We show by some examples that these phenomena are due to the presence of tipping points in the model.

  6. An evolutionary game model for behavioral gambit of loyalists: Global awareness and risk-aversion

    Science.gov (United States)

    Alfinito, E.; Barra, A.; Beccaria, M.; Fachechi, A.; Macorini, G.

    2018-02-01

    We study the phase diagram of a minority game where three classes of agents are present. Two types of agents play a risk-loving game that we model by the standard Snowdrift Game. The behaviour of the third type of agents is coded by indifference with respect to the game at all: their dynamics is designed to account for risk-aversion as an innovative behavioral gambit. From this point of view, the choice of this solitary strategy is enhanced when innovation starts, while is depressed when it becomes the majority option. This implies that the payoff matrix of the game becomes dependent on the global awareness of the agents measured by the relevance of the population of the indifferent players. The resulting dynamics is nontrivial with different kinds of phase transition depending on a few model parameters. The phase diagram is studied on regular as well as complex networks.

  7. AstraZeneca and Covance Laboratories Clinical Bioanalysis Alliance: an evolutionary outsourcing model.

    Science.gov (United States)

    Arfvidsson, Cecilia; Severin, Paul; Holmes, Victoria; Mitchell, Richard; Bailey, Christopher; Cape, Stephanie; Li, Yan; Harter, Tammy

    2017-08-01

    The AstraZeneca and Covance Laboratories Clinical Bioanalysis Alliance (CBioA) was launched in 2011 after a period of global economic recession. In this challenging environment, AstraZeneca elected to move to a full and centralized outsourcing model that could optimize the number of people supporting bioanalytical work and reduce the analytical cost. This paper describes the key aspects of CBioA, the innovative operational model implemented, and our ways of ensuring this was much more than simply a cost reduction exercise. As we have recently passed the first 5-year cycle, this paper also summarizes some of the concluding benefits, wins and lessons learned, and how we now plan to extend and develop the relationship even further moving into a new clinical laboratory partnership.

  8. Active vibration absorber for CSI evolutionary model: Design and experimental results

    Science.gov (United States)

    Bruner, Anne M.; Belvin, W. Keith; Horta, Lucas G.; Juang, Jer-Nan

    1991-01-01

    The development of control of large flexible structures technology must include practical demonstration to aid in the understanding and characterization of controlled structures in space. To support this effort, a testbed facility was developed to study practical implementation of new control technologies under realistic conditions. The design is discussed of a second order, acceleration feedback controller which acts as an active vibration absorber. This controller provides guaranteed stability margins for collocated sensor/actuator pairs in the absence of sensor/actuator dynamics and computational time delay. The primary performance objective considered is damping augmentation of the first nine structural modes. Comparison of experimental and predicted closed loop damping is presented, including test and simulation time histories for open and closed loop cases. Although the simulation and test results are not in full agreement, robustness of this design under model uncertainty is demonstrated. The basic advantage of this second order controller design is that the stability of the controller is model independent.

  9. highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models

    Directory of Open Access Journals (Sweden)

    Huai-Wei Huang

    2018-02-01

    Full Text Available Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear folding-defective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaEG69D. Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaEG69D mutants. Elevated highroad transcript levels are detected in ninaEG69D flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaEG69D flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids.

  10. Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

    Science.gov (United States)

    Bhutoria, Savita

    2016-01-01

    Abstract The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein‐protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV‐1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c‐MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

  11. Active vibration absorber for the CSI evolutionary model - Design and experimental results. [Controls Structures Interaction

    Science.gov (United States)

    Bruner, Anne M.; Belvin, W. Keith; Horta, Lucas G.; Juang, Jer-Nan

    1991-01-01

    The development of control of large flexible structures technology must include practical demonstrations to aid in the understanding and characterization of controlled structures in space. To support this effort, a testbed facility has been developed to study practical implementation of new control technologies under realistic conditions. The paper discusses the design of a second order, acceleration feedback controller which acts as an active vibration absorber. This controller provides guaranteed stability margins for collocated sensor/actuator pairs in the absence of sensor/actuator dynamics and computational time delay. Experimental results in the presence of these factors are presented and discussed. The robustness of this design under model uncertainty is demonstrated.

  12. Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jonathan Wills

    2011-03-01

    Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

  13. Managing uncertainty, ambiguity and ignorance in impact assessment by embedding evolutionary resilience, participatory modelling and adaptive management.

    Science.gov (United States)

    Bond, Alan; Morrison-Saunders, Angus; Gunn, Jill A E; Pope, Jenny; Retief, Francois

    2015-03-15

    In the context of continuing uncertainty, ambiguity and ignorance in impact assessment (IA) prediction, the case is made that existing IA processes are based on false 'normal' assumptions that science can solve problems and transfer knowledge into policy. Instead, a 'post-normal science' approach is needed that acknowledges the limits of current levels of scientific understanding. We argue that this can be achieved through embedding evolutionary resilience into IA; using participatory workshops; and emphasising adaptive management. The goal is an IA process capable of informing policy choices in the face of uncertain influences acting on socio-ecological systems. We propose a specific set of process steps to operationalise this post-normal science approach which draws on work undertaken by the Resilience Alliance. This process differs significantly from current models of IA, as it has a far greater focus on avoidance of, or adaptation to (through incorporating adaptive management subsequent to decisions), unwanted future scenarios rather than a focus on the identification of the implications of a single preferred vision. Implementing such a process would represent a culture change in IA practice as a lack of knowledge is assumed and explicit, and forms the basis of future planning activity, rather than being ignored. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The mathematical modelling of plant behaviour: an evolutionary history and forward projection: Pt. 3

    International Nuclear Information System (INIS)

    Whitmarsh-Everiss, M.J.

    1993-01-01

    The two previous articles in this series considered the evolution of analogue and hybrid computing techniques using examples from Magnox and advanced gas cooled reactor design. The parallel deployment and development of digital computing was discussed in relation to the simulation languages of the day which culminated in the formal release of the Plant Modelling Systems Program, PMSP. It is now proposed to trace the history from 1980 to the present day and discuss the highly sophisticated interactive digital computing environment known as the Plant Design Analyser. A backward step will be taken in time to look at the parallel and evolving design of Plant Operator Training Simulators. Once again, the development of these facilities had to track the evolving computer architectures and developments in computing science. During this period modelling disciplines and methodologies became formalised and were enshrined in elaborate Computer Aided Design Suites. However, they were consolidated at the end of our story. It is first our intention to discuss the simulation language PMSP as this is the foundation of the explanation which follows. (author)

  15. Particle production at energies available at the CERN Large Hadron Collider within an evolutionary model

    Science.gov (United States)

    Sinyukov, Yu. M.; Shapoval, V. M.

    2018-06-01

    The particle yields and particle number ratios in Pb+Pb collisions at the CERN Large Hadron Collider (LHC) energy √{sN N}=2.76 TeV are described within the integrated hydrokinetic model (iHKM) at two different equations of state (EoS) for quark-gluon matter and the two corresponding hadronization temperatures T =165 MeV and T =156 MeV. The role of particle interactions at the final afterburner stage of the collision in the particle production is investigated by means of comparison of the results of full iHKM simulations with those where the annihilation and other inelastic processes (except for resonance decays) are switched off after hadronization/particlization, similarly as in the thermal models. An analysis supports the picture of continuous chemical freeze-out in the sense that the corrections to the sudden chemical freeze-out results, which arise because of the inelastic reactions at the subsequent evolution times, are noticeable and improve the description of particle number ratios. An important observation is that, although the particle number ratios with switched-off inelastic reactions are quite different at different particlization temperatures which are adopted for different equations of state to reproduce experimental data, the complete iHKM calculations bring very close results in both cases.

  16. Evolutionary modeling and prediction of non-coding RNAs in Drosophila.

    Directory of Open Access Journals (Sweden)

    Robert K Bradley

    2009-08-01

    Full Text Available We performed benchmarks of phylogenetic grammar-based ncRNA gene prediction, experimenting with eight different models of structural evolution and two different programs for genome alignment. We evaluated our models using alignments of twelve Drosophila genomes. We find that ncRNA prediction performance can vary greatly between different gene predictors and subfamilies of ncRNA gene. Our estimates for false positive rates are based on simulations which preserve local islands of conservation; using these simulations, we predict a higher rate of false positives than previous computational ncRNA screens have reported. Using one of the tested prediction grammars, we provide an updated set of ncRNA predictions for D. melanogaster and compare them to previously-published predictions and experimental data. Many of our predictions show correlations with protein-coding genes. We found significant depletion of intergenic predictions near the 3' end of coding regions and furthermore depletion of predictions in the first intron of protein-coding genes. Some of our predictions are colocated with larger putative unannotated genes: for example, 17 of our predictions showing homology to the RFAM family snoR28 appear in a tandem array on the X chromosome; the 4.5 Kbp spanned by the predicted tandem array is contained within a FlyBase-annotated cDNA.

  17. Evolutionary stability and resistance to cheating in an indirect reciprocity model based on reputation

    Science.gov (United States)

    Martinez-Vaquero, Luis A.; Cuesta, José A.

    2013-05-01

    Indirect reciprocity is one of the main mechanisms to explain the emergence and sustainment of altruism in societies. The standard approach to indirect reciprocity is reputation models. These are games in which players base their decisions on their opponent's reputation gained in past interactions with other players (moral assessment). The combination of actions and moral assessment leads to a large diversity of strategies; thus determining the stability of any of them against invasions by all the others is a difficult task. We use a variant of a previously introduced reputation-based model that let us systematically analyze all these invasions and determine which ones are successful. Accordingly, we are able to identify the third-order strategies (those which, apart from the action, judge considering both the reputation of the donor and that of the recipient) that are evolutionarily stable. Our results reveal that if a strategy resists the invasion of any other one sharing its same moral assessment, it can resist the invasion of any other strategy. However, if actions are not always witnessed, cheaters (i.e., individuals with a probability of defecting regardless of the opponent's reputation) have a chance to defeat the stable strategies for some choices of the probabilities of cheating and of being witnessed. Remarkably, by analyzing this issue with adaptive dynamics we find that whether an honest population resists the invasion of cheaters is determined by a Hamilton-like rule, with the probability that the cheat is discovered playing the role of the relatedness parameter.

  18. Promise(s of mesenchymal stem cells as an in vitro model system to depict pre-diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.

    Directory of Open Access Journals (Sweden)

    Soundarya L Madhira

    Full Text Available BACKGROUND: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants, established at National Centre for Laboratory Animals (NCLAS of National Institute of Nutrition (NIN, form a suitable model system to study obesity with Type 2 diabetes (T2D demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc. The present study has been carried out to explore the potent application(s of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs, to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT, hyperinsulinemia (HI and insulin resistance (IR seen with Mutant rats akin to human situation. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of BM-MSCs (third passage from Mutants, its lean littermate (Lean and parental control (Control were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs. The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFα; increased stem cell recruitment (Oct-4, Sox-2 and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation; accelerated preadipocyte induction (Dact-1, PPARγ2 with a quantitative increase in mature adipocyte formation (Leptin; ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data. CONCLUSIONS: Given the ease of accessibility and availability of MSCs, the present study form the basis to report for

  19. Industrial Applications of Evolutionary Algorithms

    CERN Document Server

    Sanchez, Ernesto; Tonda, Alberto

    2012-01-01

    This book is intended as a reference both for experienced users of evolutionary algorithms and for researchers that are beginning to approach these fascinating optimization techniques. Experienced users will find interesting details of real-world problems, and advice on solving issues related to fitness computation, modeling and setting appropriate parameters to reach optimal solutions. Beginners will find a thorough introduction to evolutionary computation, and a complete presentation of all evolutionary algorithms exploited to solve different problems. The book could fill the gap between the

  20. Asymmetric Evolutionary Games

    Science.gov (United States)

    McAvoy, Alex; Hauert, Christoph

    2015-01-01

    Evolutionary game theory is a powerful framework for studying evolution in populations of interacting individuals. A common assumption in evolutionary game theory is that interactions are symmetric, which means that the players are distinguished by only their strategies. In nature, however, the microscopic interactions between players are nearly always asymmetric due to environmental effects, differing baseline characteristics, and other possible sources of heterogeneity. To model these phenomena, we introduce into evolutionary game theory two broad classes of asymmetric interactions: ecological and genotypic. Ecological asymmetry results from variation in the environments of the players, while genotypic asymmetry is a consequence of the players having differing baseline genotypes. We develop a theory of these forms of asymmetry for games in structured populations and use the classical social dilemmas, the Prisoner’s Dilemma and the Snowdrift Game, for illustrations. Interestingly, asymmetric games reveal essential differences between models of genetic evolution based on reproduction and models of cultural evolution based on imitation that are not apparent in symmetric games. PMID:26308326

  1. Wind Farm Layout Optimization through a Crossover-Elitist Evolutionary Algorithm performed over a High Performing Analytical Wake Model

    Science.gov (United States)

    Kirchner-Bossi, Nicolas; Porté-Agel, Fernando

    2017-04-01

    Wind turbine wakes can significantly disrupt the performance of further downstream turbines in a wind farm, thus seriously limiting the overall wind farm power output. Such effect makes the layout design of a wind farm to play a crucial role on the whole performance of the project. An accurate definition of the wake interactions added to a computationally compromised layout optimization strategy can result in an efficient resource when addressing the problem. This work presents a novel soft-computing approach to optimize the wind farm layout by minimizing the overall wake effects that the installed turbines exert on one another. An evolutionary algorithm with an elitist sub-optimization crossover routine and an unconstrained (continuous) turbine positioning set up is developed and tested over an 80-turbine offshore wind farm over the North Sea off Denmark (Horns Rev I). Within every generation of the evolution, the wind power output (cost function) is computed through a recently developed and validated analytical wake model with a Gaussian profile velocity deficit [1], which has shown to outperform the traditionally employed wake models through different LES simulations and wind tunnel experiments. Two schemes with slightly different perimeter constraint conditions (full or partial) are tested. Results show, compared to the baseline, gridded layout, a wind power output increase between 5.5% and 7.7%. In addition, it is observed that the electric cable length at the facilities is reduced by up to 21%. [1] Bastankhah, Majid, and Fernando Porté-Agel. "A new analytical model for wind-turbine wakes." Renewable Energy 70 (2014): 116-123.

  2. The Cybersemiotic Model of Communication: An Evolutionary View on the Threshold between Semiosis and Informational Exchange

    Directory of Open Access Journals (Sweden)

    Søren Brier

    2008-07-01

    Full Text Available This paper discusses various suggestions for a philosophical framework for a trans-disciplinary information science or a semiotic doctrine. These are: the mechanical materialistic, the pan-informational, the Luhmanian second order cybernetic approach, Peircian biosemiotics and finally the pan-semiotic approach. The limitations of each are analysed. The conclusion is that we will not have to choose between either a cybernetic-informational or a semiotic approach. A combination of a Peircian-based biosemiotics with autopoiesis theory, second order cybernetics and information science is suggested in a five-levelled cybersemiotic framework. The five levels are 1 a level of Firstness, 2 a level of mechanical matter, energy and force as Secondness, 3 a cybernetic and thermodynamic level of information, 4 a level of sign games and 5 a level of conscious language games. These levels are then used to differentiate levels of information systems, sign and language games in human communication. In our model Maturana and Varela’s description of the logic of the living as autopoietic is accepted and expanded with Luhmann’s generalization of the concept of autopoiesis, to cover also to psychological and socio-communicative systems. Adding a Peircian concept of semiosis to Luhmann’s theory in the framework of biosemiotics enables us to view the interplay of mind and body as a sign play. I have in a previous publication (see list of references suggested the term “sign play” pertaining to exosemiotics processes between animals in the same species by stretching Wittgenstein's language concept into the animal world of signs. The new concept of intrasemiotics designates the semiosis of the interpenetration between biological and psychological autopoietic systems as Luhmann defines them in his theory. One could therefore view intrasemiotics as the interplay between Lorenz' biological defined motivations and Freud's Id, understood as the psychological aspect

  3. Fork stalling and template switching as a mechanism for polyalanine tract expansion affecting the DYC mutant of HOXD13, a new murine model of synpolydactyly.

    Science.gov (United States)

    Cocquempot, Olivier; Brault, Véronique; Babinet, Charles; Herault, Yann

    2009-09-01

    Polyalanine expansion diseases are proposed to result from unequal crossover of sister chromatids that increases the number of repeats. In this report we suggest an alternative mechanism we put forward while we investigated a new spontaneous mutant that we named "Dyc" for "Digit in Y and Carpe" phenotype. Phenotypic analysis revealed an abnormal limb patterning similar to that of the human inherited congenital disease synpolydactyly (SPD) and to the mouse mutant model Spdh. Both human SPD and mouse Spdh mutations affect the Hoxd13 gene within a 15-residue polyalanine-encoding repeat in the first exon of the gene, leading to a dominant negative HOXD13. Genetic analysis of the Dyc mutant revealed a trinucleotide expansion in the polyalanine-encoding region of the Hoxd13 gene resulting in a 7-alanine expansion. However, unlike the Spdh mutation, this expansion cannot result from a simple duplication of a short segment. Instead, we propose the fork stalling and template switching (FosTeS) described for generation of nonrecurrent genomic rearrangements as a possible mechanism for the Dyc polyalanine extension, as well as for other polyalanine expansions described in the literature and that could not be explained by unequal crossing over.

  4. Multi-Objective Optimization of the Hedging Model for reservoir Operation Using Evolutionary Algorithms

    Directory of Open Access Journals (Sweden)

    sadegh sadeghitabas

    2015-12-01

    Full Text Available Multi-objective problems rarely ever provide a single optimal solution, rather they yield an optimal set of outputs (Pareto fronts. Solving these problems was previously accomplished by using some simplifier methods such as the weighting coefficient method used for converting a multi-objective problem to a single objective function. However, such robust tools as multi-objective meta-heuristic algorithms have been recently developed for solving these problems. The hedging model is one of the classic problems for reservoir operation that is generally employed for mitigating drought impacts in water resources management. According to this method, although it is possible to supply the total planned demands, only portions of the demands are met to save water by allowing small deficits in the current conditions in order to avoid or reduce severe deficits in future. The approach heavily depends on economic and social considerations. In the present study, the meta-heuristic algorithms of NSGA-II, MOPSO, SPEA-II, and AMALGAM are used toward the multi-objective optimization of the hedging model. For this purpose, the rationing factors involved in Taleghan dam operation are optimized over a 35-year statistical period of inflow. There are two objective functions: a minimizing the modified shortage index, and b maximizing the reliability index (i.e., two opposite objectives. The results show that the above algorithms are applicable to a wide range of optimal solutions. Among the algorithms, AMALGAM is found to produce a better Pareto front for the values of the objective function, indicating its more satisfactory performance.

  5. Mass loss from red giants - A simple evolutionary model for NGC 7027

    Science.gov (United States)

    Jura, M.

    1984-01-01

    NGC 7027 is a young planetary nebula with the remnants of a red giant circumstellar envelope surrounding the central, ionized region. By comparing the outer molecular envelope with the inner ionized material, it is argued that the mass loss rate has decreased by at least a factor of 3, and more probably by about a factor of 10, during the past 1000 years. From this result, it is argued that the luminosity of the central star has also decreased substantially during the same time, consistent with models for the rapid evolution of stars just after they evolve off the asymptotic giant branch. In this picture, the distance to NGC 7027 is less than 1300 pc. NGC 7027 was the last (and best) example of a star where apparently the momentum in the outflowing mass /M(dot)v/ is considerably greater than the momentum in the radiation field (L/c). With the above description of this object, the evidence is now strong that quite often the mass lost from late-type giants is ultimately driven to infinity by radiation pressure on grains. If M(dot)v is as large as L/c for asymptotic branch stars, then it is expected that the total amount of mass lost during this stage of evolution is of the same magnitude as the initial mass of the star, and therefore this mass loss can profoundly affect the star's ultimate fate.

  6. Estimation of dual phase lag model parameters using the evolutionary algorithms

    Directory of Open Access Journals (Sweden)

    B. Mochnacki

    2011-07-01

    Full Text Available Generalization of Fourier law, in particular the introduction of two ‘delay times’ (relaxation time q and thermalization time T leads to thenew form of energy equation called the dual-phase-lag model (DPLM. This equation should be applied in a case of microscale heat transfermodeling. In particular, DPLM constitutes a good approximation of thermal processes which are characterized by extremely short duration(e.g. ultrafast laser pulse, extreme temperature gradients and geometrical features of domain considered (e.g. thin metal film. The aim ofconsiderations presented in this paper is the identification of two above mentioned positive constants q, T. They correspond to the relaxationtime, which is the mean time for electrons to change their energy states and the thermalization time, which is the mean time required forc(TTl G(TT electrons and lattice to reach equilibrium. In this paper the DPlLMlequation ise appllied for analysis of thermal processes proceeding in a thint metal film subjected to a laser beam. At the stage of computations connected with the identification problem solution the evolutionaryalgorithms are used. To solve the problem the additional information concerning the transient temperature distribution on a metal film surface is assumed to be known.

  7. Effect of binary stars on the dynamical evolution of stellar clusters. II. Analytic evolutionary models

    International Nuclear Information System (INIS)

    Hills, J.G.

    1975-01-01

    We use analytic models to compute the evolution of the core of a stellar system due simultaneously to stellar evaporation which causes the system (core) to contract and to its binaries which cause it to expand by progressively decreasing its binding energy. The evolution of the system is determined by two parameters: the initial number of stars in the system N 0 , and the fraction f/subb/ of its stars which are binaries. For a fixed f/subb/, stellar evaporation initially dominates the dynamical evolution if N 0 is sufficiently large due to the fact that the rate of evaporation is determined chiefly by long-range encounters which increase in importance as the number of stars in the system increases. If stellar evaporation initially dominates, the system first contracts, but as N/subc/, the number of remaining stars in the system, decreases by evaporation, the system reaches a minimum radius and a maximum density and then it expands monotonically as N/subc/ decreases further. Open clusters expand monotonically from the beginning if they have anything approaching average Population I binary frequencies. Globular clusters are highly deficient in binaries in order to have formed and retained the high-density stellar cores observed in most of them. We estimate that for these system f/subb/ < or = 0.15

  8. On economic applications of evolutionary game theory

    OpenAIRE

    Daniel Friedman

    1998-01-01

    Evolutionary games have considerable unrealized potential for modeling substantive economic issues. They promise richer predictions than orthodox game models but often require more extensive specifications. This paper exposits the specification of evolutionary game models and classifies the possible asymptotic behavior for one and two dimensional models.

  9. Modeling Temporal Variation in Social Network: An Evolutionary Web Graph Approach

    Science.gov (United States)

    Mitra, Susanta; Bagchi, Aditya

    A social network is a social structure between actors (individuals, organization or other social entities) and indicates the ways in which they are connected through various social relationships like friendships, kinships, professional, academic etc. Usually, a social network represents a social community, like a club and its members or a city and its citizens etc. or a research group communicating over Internet. In seventies Leinhardt [1] first proposed the idea of representing a social community by a digraph. Later, this idea became popular among other research workers like, network designers, web-service application developers and e-learning modelers. It gave rise to a rapid proliferation of research work in the area of social network analysis. Some of the notable structural properties of a social network are connectedness between actors, reachability between a source and a target actor, reciprocity or pair-wise connection between actors with bi-directional links, centrality of actors or the important actors having high degree or more connections and finally the division of actors into sub-structures or cliques or strongly-connected components. The cycles present in a social network may even be nested [2, 3]. The formal definition of these structural properties will be provided in Sect. 8.2.1. The division of actors into cliques or sub-groups can be a very important factor for understanding a social structure, particularly the degree of cohesiveness in a community. The number, size, and connections among the sub-groups in a network are useful in understanding how the network, as a whole, is likely to behave.

  10. Structural, functional and evolutionary study of in silico three dimensional model of pneumolysin

    International Nuclear Information System (INIS)

    Lutfullah, G.; Taj, S.; Bashir, K.; Khattak, S.U.

    2017-01-01

    Streptococcus pneumoniae, a gram-positive cocci shaped bacteria, is the major human pathogen, causing diseases like septic meningitis, otitis media, sinusitis, pneumonia and septicemia. The objective of present study is to gain more knowledge about the function of important domain of the toxin pneumolysin. This study aims to analyze the structural and functional features of pneumolysin and to investigate the residues involved in its pathogenicity.The major virulence factor of this bacterium is a protein, pneumolysin, which is the member of thiol-activated cytolysins. From the three dimensional homology model of the present study, it was found that pneumolysin has four domains, out of which domain 4 is of great importance. It was observed that Cys 428 and Trp 433 of pneumolysin are of great importance and any mutation in this region highly reduces its cytotoxicity. Cys 428 forms hydrophobic contact with Ala 373 and Trp 436 of the conserved region, while Trp 433 is bonded with Trp 436 and Arg 426 through hydrogen interactions .The particular cysteine residue is present at position 428 and is also sandwiched between beta-sheet and Trp 436. In pneumolysin, the undecapeptide or the Trp-rich loop spans the region (amino acid 427 to 437) and several single amino acid substitutions within this region reduce the cytolytic activity of pneumolysin by up to 99.9% as reported previously. The primary structure of pneumolysin has a total eight tryptophan residues and one cysteine. The undecapeptide region has three tryptophan and one cysteine residue containing 11 amino acid sequence i.e ECTGLAWEWWR. Cysteine 428 of pneumolysin present in trp-rich motif is responsible to act on cholestrol. Pairwise alignment reveals that pneumolysin do not have the N-terminus signal peptide sequence which is present in the template i.e. perfringolysin. This shows that pneumolysin is an intracellular protein and released only upon cell lysis. (author)

  11. From Mimicry to Language: A Neuroanatomically Based Evolutionary Model of the Emergence of Vocal Language

    Science.gov (United States)

    Poliva, Oren

    2016-01-01

    The auditory cortex communicates with the frontal lobe via the middle temporal gyrus (auditory ventral stream; AVS) or the inferior parietal lobule (auditory dorsal stream; ADS). Whereas the AVS is ascribed only with sound recognition, the ADS is ascribed with sound localization, voice detection, prosodic perception/production, lip-speech integration, phoneme discrimination, articulation, repetition, phonological long-term memory and working memory. Previously, I interpreted the juxtaposition of sound localization, voice detection, audio-visual integration and prosodic analysis, as evidence that the behavioral precursor to human speech is the exchange of contact calls in non-human primates. Herein, I interpret the remaining ADS functions as evidence of additional stages in language evolution. According to this model, the role of the ADS in vocal control enabled early Homo (Hominans) to name objects using monosyllabic calls, and allowed children to learn their parents' calls by imitating their lip movements. Initially, the calls were forgotten quickly but gradually were remembered for longer periods. Once the representations of the calls became permanent, mimicry was limited to infancy, and older individuals encoded in the ADS a lexicon for the names of objects (phonological lexicon). Consequently, sound recognition in the AVS was sufficient for activating the phonological representations in the ADS and mimicry became independent of lip-reading. Later, by developing inhibitory connections between acoustic-syllabic representations in the AVS and phonological representations of subsequent syllables in the ADS, Hominans became capable of concatenating the monosyllabic calls for repeating polysyllabic words (i.e., developed working memory). Finally, due to strengthening of connections between phonological representations in the ADS, Hominans became capable of encoding several syllables as a single representation (chunking). Consequently, Hominans began vocalizing and

  12. [On the problems of the evolutionary optimization of life history. II. To justification of optimization criterion for nonlinear Leslie model].

    Science.gov (United States)

    Pasekov, V P

    2013-03-01

    The paper considers the problems in the adaptive evolution of life-history traits for individuals in the nonlinear Leslie model of age-structured population. The possibility to predict adaptation results as the values of organism's traits (properties) that provide for the maximum of a certain function of traits (optimization criterion) is studied. An ideal criterion of this type is Darwinian fitness as a characteristic of success of an individual's life history. Criticism of the optimization approach is associated with the fact that it does not take into account the changes in the environmental conditions (in a broad sense) caused by evolution, thereby leading to losses in the adequacy of the criterion. In addition, the justification for this criterion under stationary conditions is not usually rigorous. It has been suggested to overcome these objections in terms of the adaptive dynamics theory using the concept of invasive fitness. The reasons are given that favor the application of the average number of offspring for an individual, R(L), as an optimization criterion in the nonlinear Leslie model. According to the theory of quantitative genetics, the selection for fertility (that is, for a set of correlated quantitative traits determined by both multiple loci and the environment) leads to an increase in R(L). In terms of adaptive dynamics, the maximum R(L) corresponds to the evolutionary stability and, in certain cases, convergent stability of the values for traits. The search for evolutionarily stable values on the background of limited resources for reproduction is a problem of linear programming.

  13. Tracing hepatitis B virus (HBV genotype B5 (formerly B6 evolutionary history in the circumpolar Arctic through phylogeographic modelling

    Directory of Open Access Journals (Sweden)

    Remco Bouckaert

    2017-08-01

    Full Text Available Background Indigenous populations of the circumpolar Arctic are considered to be endemically infected (>2% prevalence with hepatitis B virus (HBV, with subgenotype B5 (formerly B6 unique to these populations. The distinctive properties of HBV/B5, including high nucleotide diversity yet no significant liver disease, suggest virus adaptation through long-term host-pathogen association. Methods To investigate the origin and evolutionary spread of HBV/B5 into the circumpolar Arctic, fifty-seven partial and full genome sequences from Alaska, Canada and Greenland, having known location and sampling dates spanning 40 years, were phylogeographically investigated by Bayesian analysis (BEAST 2 using a reversible-jump-based substitution model and a clock rate estimated at 4.1 × 10−5 substitutions/site/year. Results Following an initial divergence from an Asian viral ancestor approximately 1954 years before present (YBP; 95% highest probability density interval [1188, 2901], HBV/B5 coalescence occurred almost 1000 years later. Surprisingly, the HBV/B5 ancestor appears to locate first to Greenland in a rapid coastal route progression based on the landscape aware geographic model, with subsequent B5 evolution and spread westward. Bayesian skyline plot analysis demonstrated an HBV/B5 population expansion occurring approximately 400 YBP, coinciding with the disruption of the Neo-Eskimo Thule culture into more heterogeneous and regionally distinct Inuit populations throughout the North American Arctic. Discussion HBV/B5 origin and spread appears to occur coincident with the movement of Neo-Eskimo (Inuit populations within the past 1000 years, further supporting the hypothesis of HBV/host co-expansion, and illustrating the concept of host-pathogen adaptation and balance.

  14. Mechanism of enhanced conversion of 1,2,3-trichloropropane by mutant haloalkane dehalogenase revealed by molecular modeling

    Science.gov (United States)

    Banáš, Pavel; Otyepka, Michal; Jeřábek, Petr; Petřek, Martin; Damborský, Jiří

    2006-06-01

    1,2,3-Trichloropropane (TCP) is a highly toxic, recalcitrant byproduct of epichlorohydrin manufacture. Haloalkane dehalogenase (DhaA) from Rhodococcus sp. hydrolyses the carbon-halogen bond in various halogenated compounds including TCP, but with low efficiency ( k cat/ K m = 36 s-1 M-1). A Cys176Tyr-DhaA mutant with a threefold higher catalytic efficiency for TCP dehalogenation has been previously obtained by error-prone PCR. We have used molecular simulations and quantum mechanical calculations to elucidate the molecular mechanisms involved in the improved catalysis of the mutant, and enantioselectivity of DhaA toward TCP. The Cys176Tyr mutation modifies the protein access and export routes. Substitution of the Cys residue by the bulkier Tyr narrows the upper tunnel, making the second tunnel "slot" the preferred route. TCP can adopt two major orientations in the DhaA enzyme, in one of which the halide-stabilizing residue Asn41 forms a hydrogen bond with the terminal halogen atom of the TCP molecule, while in the other it bonds with the central halogen atom. The differences in these binding patterns explain the preferential formation of the ( R)- over the ( S)-enantiomer of 2,3-dichloropropane-1-ol in the reaction catalyzed by the enzyme.

  15. A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

    Science.gov (United States)

    Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

    2018-01-01

    Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces

  16. Computational identification of adaptive mutants using the VERT system

    Directory of Open Access Journals (Sweden)

    Winkler James

    2012-04-01

    Full Text Available Background Evolutionary dynamics of microbial organisms can now be visualized using the Visualizing Evolution in Real Time (VERT system, in which several isogenic strains expressing different fluorescent proteins compete during adaptive evolution and are tracked using fluorescent cell sorting to construct a population history over time. Mutations conferring enhanced growth rates can be detected by observing changes in the fluorescent population proportions. Results Using data obtained from several VERT experiments, we construct a hidden Markov-derived model to detect these adaptive events in VERT experiments without external intervention beyond initial training. Analysis of annotated data revealed that the model achieves consensus with human annotation for 85-93% of the data points when detecting adaptive events. A method to determine the optimal time point to isolate adaptive mutants is also introduced. Conclusions The developed model offers a new way to monitor adaptive evolution experiments without the need for external intervention, thereby simplifying adaptive evolution efforts relying on population tracking. Future efforts to construct a fully automated system to isolate adaptive mutants may find the algorithm a useful tool.

  17. Social Defense: An Evolutionary-Developmental Model of Children's Strategies for Coping with Threat in the Peer Group

    Directory of Open Access Journals (Sweden)

    Meredith J. Martin

    2014-04-01

    Full Text Available Navigating the ubiquitous conflict, competition, and complex group dynamics of the peer group is a pivotal developmental task of childhood. Difficulty negotiating these challenges represents a substantial source of risk for psychopathology. Evolutionary developmental psychology offers a unique perspective with the potential to reorganize the way we think about the role of peer relationships in shaping how children cope with the everyday challenges of establishing a social niche. To address this gap, we utilize the ethological reformulation of the emotional security theory as a guide to developing an evolutionary framework for advancing an understanding of the defense strategies children use to manage antagonistic peer relationships and protect themselves from interpersonal threat (Davies and Sturge-Apple, 2007. In this way, we hope to illustrate the value of an evolutionary developmental lens in generating unique theoretical insight and novel research directions into the role of peer relationships in the development of psychopathology.

  18. An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1.

    Directory of Open Access Journals (Sweden)

    Sergei L Kosakovsky Pond

    2009-11-01

    Full Text Available Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1 are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and detection of novel variants, e.g., circulating recombinant forms in HIV-1. A number of conceptually and technically different techniques have been proposed for determining the subtype of a query sequence, but there is not a universally optimal approach. We present a model-based phylogenetic method for automatically subtyping an HIV-1 (or other viral or bacterial sequence, mapping the location of breakpoints and assigning parental sequences in recombinant strains as well as computing confidence levels for the inferred quantities. Our Subtype Classification Using Evolutionary ALgorithms (SCUEAL procedure is shown to perform very well in a variety of simulation scenarios, runs in parallel when multiple sequences are being screened, and matches or exceeds the performance of existing approaches on typical empirical cases. We applied SCUEAL to all available polymerase (pol sequences from two large databases, the Stanford Drug Resistance database and the UK HIV Drug Resistance Database. Comparing with subtypes which had previously been assigned revealed that a minor but substantial (approximately 5% fraction of pure subtype sequences may in fact be within- or inter-subtype recombinants. A free implementation of SCUEAL is provided as a module for the HyPhy package and the Datamonkey web server. Our method is especially useful when an accurate automatic classification of an unknown strain is desired, and is positioned to complement and extend faster but less accurate methods. Given the increasingly frequent use of HIV subtype information in studies focusing on the effect of subtype on treatment, clinical outcome, pathogenicity and vaccine design, the importance

  19. Evolutionary games on graphs

    Science.gov (United States)

    Szabó, György; Fáth, Gábor

    2007-07-01

    Game theory is one of the key paradigms behind many scientific disciplines from biology to behavioral sciences to economics. In its evolutionary form and especially when the interacting agents are linked in a specific social network the underlying solution concepts and methods are very similar to those applied in non-equilibrium statistical physics. This review gives a tutorial-type overview of the field for physicists. The first four sections introduce the necessary background in classical and evolutionary game theory from the basic definitions to the most important results. The fifth section surveys the topological complications implied by non-mean-field-type social network structures in general. The next three sections discuss in detail the dynamic behavior of three prominent classes of models: the Prisoner's Dilemma, the Rock-Scissors-Paper game, and Competing Associations. The major theme of the review is in what sense and how the graph structure of interactions can modify and enrich the picture of long term behavioral patterns emerging in evolutionary games.

  20. Evolutionary mysteries in meiosis.

    Science.gov (United States)

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E; Wijnker, Erik; Haag, Christoph R

    2016-10-19

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often 'weird' features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'. © 2016 The Author(s).

  1. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  2. Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models.

    Directory of Open Access Journals (Sweden)

    Marcelo R Vargas

    Full Text Available The nuclear factor erythroid 2-related factor 2 (Nrf2 governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 cause familial forms of amyotrophic lateral sclerosis (ALS, a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1(G93A mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS.

  3. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  4. Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

    Directory of Open Access Journals (Sweden)

    Cristi L. Galindo

    2009-01-01

    Full Text Available We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT Y. pestis CO92 and its Braun lipoprotein (Δlpp mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS- associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague.

  5. Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: a putative model of gene × environment interaction.

    Science.gov (United States)

    Desbonnet, Lieve; O'Tuathaigh, Colm; Clarke, Gerard; O'Leary, Claire; Petit, Emilie; Clarke, Niamh; Tighe, Orna; Lai, Donna; Harvey, Richard; Cryan, John F; Dinan, Timothy G; Waddington, John L

    2012-05-01

    There is a paucity of animal models by which the contributions of environmental and genetic factors to the pathobiology of psychosis can be investigated. This study examined the individual and combined effects of chronic social stress during adolescence and deletion of the schizophrenia risk gene neuregulin-1 (NRG1) on adult mouse phenotype. Mice were exposed to repeated social defeat stress during adolescence and assessed for exploratory behaviour, working memory, sucrose preference, social behaviour and prepulse inhibition in adulthood. Thereafter, in vitro cytokine responses to mitogen stimulation and corticosterone inhibition were assayed in spleen cells, with measurement of cytokine and brain-derived neurotrophic factor (BDNF) mRNA in frontal cortex, hippocampus and striatum. NRG1 mutants exhibited hyperactivity, decreased anxiety, impaired sensorimotor gating and reduced preference for social novelty. The effects of stress on exploratory/anxiety-related parameters, spatial working memory, sucrose preference and basal cytokine levels were modified by NRG1 deletion. Stress also exerted varied effect on spleen cytokine response to concanavalin A and brain cytokine and BDNF mRNA expression in NRG1 mutants. The experience of psychosocial stress during adolescence may trigger further pathobiological features that contribute to the development of schizophrenia, particularly in those with underlying NRG1 gene abnormalities. This model elaborates the importance of gene × environment interactions in the etiology of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Modeling the milling tool wear by using an evolutionary SVM-based model from milling runs experimental data

    Science.gov (United States)

    Nieto, Paulino José García; García-Gonzalo, Esperanza; Vilán, José Antonio Vilán; Robleda, Abraham Segade

    2015-12-01

    The main aim of this research work is to build a new practical hybrid regression model to predict the milling tool wear in a regular cut as well as entry cut and exit cut of a milling tool. The model was based on Particle Swarm Optimization (PSO) in combination with support vector machines (SVMs). This optimization mechanism involved kernel parameter setting in the SVM training procedure, which significantly influences the regression accuracy. Bearing this in mind, a PSO-SVM-based model, which is based on the statistical learning theory, was successfully used here to predict the milling tool flank wear (output variable) as a function of the following input variables: the time duration of experiment, depth of cut, feed, type of material, etc. To accomplish the objective of this study, the experimental dataset represents experiments from runs on a milling machine under various operating conditions. In this way, data sampled by three different types of sensors (acoustic emission sensor, vibration sensor and current sensor) were acquired at several positions. A second aim is to determine the factors with the greatest bearing on the milling tool flank wear with a view to proposing milling machine's improvements. Firstly, this hybrid PSO-SVM-based regression model captures the main perception of statistical learning theory in order to obtain a good prediction of the dependence among the flank wear (output variable) and input variables (time, depth of cut, feed, etc.). Indeed, regression with optimal hyperparameters was performed and a determination coefficient of 0.95 was obtained. The agreement of this model with experimental data confirmed its good performance. Secondly, the main advantages of this PSO-SVM-based model are its capacity to produce a simple, easy-to-interpret model, its ability to estimate the contributions of the input variables, and its computational efficiency. Finally, the main conclusions of this study are exposed.

  7. Promising rice mutants

    International Nuclear Information System (INIS)

    Hakim, L.; Azam, M.A.; Miah, A.J.; Mansur, M.A.; Akanda, H.R.

    1988-01-01

    Two induced mutants namely, Mut NS 1 (tall) and Mut NS 5 (semi-dwarf) derived from rice variety Nizersail were evaluated for various agronomic characters at four locations in Bangladesh. Both the mutants matured about three weeks earlier and yielded significantly higher than the parent variety Nizersail. (author). 3 tabs., 9 refs

  8. CCS Site Optimization by Applying a Multi-objective Evolutionary Algorithm to Semi-Analytical Leakage Models

    Science.gov (United States)

    Cody, B. M.; Gonzalez-Nicolas, A.; Bau, D. A.

    2011-12-01

    Carbon capture and storage (CCS) has been proposed as a method of reducing global carbon dioxide (CO2) emissions. Although CCS has the potential to greatly retard greenhouse gas loading to the atmosphere while cleaner, more sustainable energy solutions are developed, there is a possibility that sequestered CO2 may leak and intrude into and adversely affect groundwater resources. It has been reported [1] that, while CO2 intrusion typically does not directly threaten underground drinking water resources, it may cause secondary effects, such as the mobilization of hazardous inorganic constituents present in aquifer minerals and changes in pH values. These risks must be fully understood and minimized before CCS project implementation. Combined management of project resources and leakage risk is crucial for the implementation of CCS. In this work, we present a method of: (a) minimizing the total CCS cost, the summation of major project costs with the cost associated with CO2 leakage; and (b) maximizing the mass of injected CO2, for a given proposed sequestration site. Optimization decision variables include the number of CO2 injection wells, injection rates, and injection well locations. The capital and operational costs of injection wells are directly related to injection well depth, location, injection flow rate, and injection duration. The cost of leakage is directly related to the mass of CO2 leaked through weak areas, such as abandoned oil wells, in the cap rock layers overlying the injected formation. Additional constraints on fluid overpressure caused by CO2 injection are imposed to maintain predefined effective stress levels that prevent cap rock fracturing. Here, both mass leakage and fluid overpressure are estimated using two semi-analytical models based upon work by [2,3]. A multi-objective evolutionary algorithm coupled with these semi-analytical leakage flow models is used to determine Pareto-optimal trade-off sets giving minimum total cost vs. maximum mass

  9. Mutant heterosis in rice

    International Nuclear Information System (INIS)

    1987-01-01

    In the variety TKM6 a high yielding semidwarf mutant has been induced. This TKM6 mutant was used in test crosses with a number of other varieties and mutants to examine the extent of heterosis of dwarfs in rice and to select superior crosses. An excerpt of the published data is given. It appears from the backcross of the mutant with its original variety, that an increase in number of productive tillers occurs in the hybrid, leading to a striking grain yield increase, while the semi-dwarf culm length (the main mutant character) reverts to the normal phenotype. In the cross with IR8 on the other hand, there is only a minimal increase in tiller number but a substantial increase in TGW leading to more than 30% yield increase over the better parent

  10. Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

    Directory of Open Access Journals (Sweden)

    Maia Amanda M

    2012-07-01

    Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

  11. Distinct Neurodegenerative Changes in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia Linked to Mutant TAU Protein

    Directory of Open Access Journals (Sweden)

    Marc Ehrlich

    2015-07-01

    Full Text Available Frontotemporal dementia (FTD is a frequent form of early-onset dementia and can be caused by mutations in MAPT encoding the microtubule-associated protein TAU. Because of limited availability of neural cells from patients’ brains, the underlying mechanisms of neurodegeneration in FTD are poorly understood. Here, we derived induced pluripotent stem cells (iPSCs from individuals with FTD-associated MAPT mutations and differentiated them into mature neurons. Patient iPSC-derived neurons demonstrated pronounced TAU pathology with increased fragmentation and phospho-TAU immunoreactivity, decreased neurite extension, and increased but reversible oxidative stress response to inhibition of mitochondrial respiration. Furthermore, FTD neurons showed an activation of the unfolded protein response, and a transcriptome analysis demonstrated distinct, disease-associated gene expression profiles. These findings indicate distinct neurodegenerative changes in FTD caused by mutant TAU and highlight the unique opportunity to use neurons differentiated from patient-specific iPSCs to identify potential targets for drug screening purposes and therapeutic intervention.

  12. Attractive evolutionary equilibria

    NARCIS (Netherlands)

    Joosten, Reinoud A.M.G.; Roorda, Berend

    2011-01-01

    We present attractiveness, a refinement criterion for evolutionary equilibria. Equilibria surviving this criterion are robust to small perturbations of the underlying payoff system or the dynamics at hand. Furthermore, certain attractive equilibria are equivalent to others for certain evolutionary

  13. BANYAN. IV. Fundamental parameters of low-mass star candidates in nearby young stellar kinematic groups—isochronal age determination using magnetic evolutionary models

    Energy Technology Data Exchange (ETDEWEB)

    Malo, Lison; Doyon, René; Albert, Loïc; Lafrenière, David; Artigau, Étienne; Gagné, Jonathan [Département de physique and Observatoire du Mont-Mégantic, Université de Montréal, Montréal, QC H3C 3J7 (Canada); Feiden, Gregory A. [Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala (Sweden); Riedel, Adric, E-mail: malo@cfht.hawaii.edu, E-mail: doyon@astro.umontreal.ca [Department of Astrophysics, American Museum of Natural History, Central Park West at 79th Street, New York, NY 10024 (United States)

    2014-09-01

    Based on high-resolution optical spectra obtained with ESPaDOnS at Canada-France-Hawaii Telescope, we determine fundamental parameters (T {sub eff}, R, L {sub bol}, log g, and metallicity) for 59 candidate members of nearby young kinematic groups. The candidates were identified through the BANYAN Bayesian inference method of Malo et al., which takes into account the position, proper motion, magnitude, color, radial velocity, and parallax (when available) to establish a membership probability. The derived parameters are compared to Dartmouth magnetic evolutionary models and field stars with the goal of constraining the age of our candidates. We find that, in general, low-mass stars in our sample are more luminous and have inflated radii compared to older stars, a trend expected for pre-main-sequence stars. The Dartmouth magnetic evolutionary models show a good fit to observations of field K and M stars, assuming a magnetic field strength of a few kG, as typically observed for cool stars. Using the low-mass members of the β Pictoris moving group, we have re-examined the age inconsistency problem between lithium depletion age and isochronal age (Hertzspring-Russell diagram). We find that the inclusion of the magnetic field in evolutionary models increases the isochronal age estimates for the K5V-M5V stars. Using these models and field strengths, we derive an average isochronal age between 15 and 28 Myr and we confirm a clear lithium depletion boundary from which an age of 26 ± 3 Myr is derived, consistent with previous age estimates based on this method.

  14. How Life History Can Sway the Fixation Probability of Mutants

    Science.gov (United States)

    Li, Xiang-Yi; Kurokawa, Shun; Giaimo, Stefano; Traulsen, Arne

    2016-01-01

    In this work, we study the effects of demographic structure on evolutionary dynamics when selection acts on reproduction, survival, or both. In contrast to the previously discovered pattern that the fixation probability of a neutral mutant decreases while the population becomes younger, we show that a mutant with a constant selective advantage may have a maximum or a minimum of the fixation probability in populations with an intermediate fraction of young individuals. This highlights the importance of life history and demographic structure in studying evolutionary dynamics. We also illustrate the fundamental differences between selection on reproduction and selection on survival when age structure is present. In addition, we evaluate the relative importance of size and structure of the population in determining the fixation probability of the mutant. Our work lays the foundation for also studying density- and frequency-dependent effects in populations when demographic structures cannot be neglected. PMID:27129737

  15. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General Article Volume 21 Issue 9 September 2016 pp 803- ... Keywords. Evolutionary game theory, evolutionary stable state, conflict, cooperation, biological games.

  16. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2016-10-01

    The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic microsatellite unstable cancers. We observed that 25 (62.5 %) out of 40 assessable Lynch syndrome-associated carcinomas lacked evidence of polypous growth, compared to 17 (50 %) out of 34 sporadic MSI-H cancers. We detected CTNNB1 mutations in 8 (17.4 %) out of 46 Lynch syndrome-associated cancers compared to 0 out of 34 sporadic MSI-H cancers (p = 0.01). The majority of CTNNB1-mutant cancers presented with a histological appearance suggesting immediate invasive growth. Our results suggest that a distinct subgroup of CRCs in Lynch syndrome may in fact emerge from a non-polypous precursor, thus potentially explaining the phenomenon of interval cancers. Such a non-polypous precursor may be the recently described mismatch repair-deficient crypt focus, which remains invisible for the examiner during colonoscopy. This calls for considering the implementation of active, primary preventive measures in the management of Lynch syndrome. Future studies on pathogenic pathways and precursor lesions in Lynch syndrome are strongly encouraged, and the clinical efficacy of new prevention approaches should be evaluated in prospective clinical trials.

  17. Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation

    Science.gov (United States)

    BenMohamed, Lbachir; Osorio, Nelson; Srivastava, Ruchi; Khan, Arif A.; Simpson, Jennifer L.; Wechsler, Steven L.

    2015-01-01

    Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the explant TG induced reactivation model in mice. The eyes of mice latently infected with wild type HSV-1 strain McKrae (LAT(+) virus) or dLAT2903 (LAT(−) virus) were irradiated with UV-B and reactivation was determined. We found that compared to LAT(−) virus, LAT(+) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B induced reactivation model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs are discussed. PMID:26002839

  18. Passivity and Evolutionary Game Dynamics

    KAUST Repository

    Park, Shinkyu; Shamma, Jeff S.; Martins, Nuno C.

    2018-01-01

    This paper investigates an energy conservation and dissipation -- passivity -- aspect of dynamic models in evolutionary game theory. We define a notion of passivity using the state-space representation of the models, and we devise systematic methods to examine passivity and to identify properties of passive dynamic models. Based on the methods, we describe how passivity is connected to stability in population games and illustrate stability of passive dynamic models using numerical simulations.

  19. Passivity and Evolutionary Game Dynamics

    KAUST Repository

    Park, Shinkyu

    2018-03-21

    This paper investigates an energy conservation and dissipation -- passivity -- aspect of dynamic models in evolutionary game theory. We define a notion of passivity using the state-space representation of the models, and we devise systematic methods to examine passivity and to identify properties of passive dynamic models. Based on the methods, we describe how passivity is connected to stability in population games and illustrate stability of passive dynamic models using numerical simulations.

  20. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model

    Science.gov (United States)

    Chen, Song; Wang, Chenran; Yeo, Syn; Liang, Chun-Chi; Okamoto, Takako; Sun, Shaogang; Wen, Jian; Guan, Jun-Lin

    2016-01-01

    Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13. We found that residues 582–585 (LQFL) in FIP200 are required for interaction with Atg13, and mutation of these residues to AAAA (designated the FIP200-4A mutant) abolished its canonical autophagy function in vitro. Furthermore, we created a FIP200-4A mutant knock-in mouse model and found that specifically blocking FIP200 interaction with Atg13 abolishes autophagy in vivo, providing direct support for the essential role of the ULK1/Atg13/FIP200/Atg101 complex in the process beyond previous studies relying on the complete knockout of individual components. Analysis of the new mouse model showed that nonautophagic functions of FIP200 are sufficient to fully support embryogenesis by maintaining a protective role in TNFα-induced apoptosis. However, FIP200-mediated canonical autophagy is required to support neonatal survival and tumor cell growth. These studies provide the first genetic evidence linking an Atg's autophagy and nonautophagic functions to different biological processes in vivo. PMID:27013233

  1. Aggregation of Trp > Glu point mutants of human gamma-D crystallin provides a model for hereditary or UV-induced cataract.

    Science.gov (United States)

    Serebryany, Eugene; Takata, Takumi; Erickson, Erika; Schafheimer, Nathaniel; Wang, Yongting; King, Jonathan A

    2016-06-01

    Numerous mutations and covalent modifications of the highly abundant, long-lived crystallins of the eye lens cause their aggregation leading to progressive opacification of the lens, cataract. The nature and biochemical mechanisms of the aggregation process are poorly understood, as neither amyloid nor native-state polymers are commonly found in opaque lenses. The βγ-crystallin fold contains four highly conserved buried tryptophans, which can be oxidized to more hydrophilic products, such as kynurenine, upon UV-B irradiation. We mimicked this class of oxidative damage using Trp→Glu point mutants of human γD-crystallin. Such substitutions may represent a model of UV-induced photodamage-introduction of a charged group into the hydrophobic core generating "denaturation from within." The effects of Trp→Glu substitutions were highly position dependent. While each was destabilizing, only the two located in the bottom of the double Greek key fold-W42E and W130E-yielded robust aggregation of partially unfolded intermediates at 37°C and pH 7. The αB-crystallin chaperone suppressed aggregation of W130E, but not W42E, indicating distinct aggregation pathways from damage in the N-terminal vs C-terminal domain. The W130E aggregates had loosely fibrillar morphology, yet were nonamyloid, noncovalent, showed little surface hydrophobicity, and formed at least 20°C below the melting temperature of the native β-sheets. These features are most consistent with domain-swapped polymerization. Aggregation of partially destabilized crystallins under physiological conditions, as occurs in this class of point mutants, could provide a simple in vitro model system for drug discovery and optimization. © 2016 The Protein Society.

  2. Mutant power: using mutant allele collections for yeast functional genomics.

    Science.gov (United States)

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Complexity in Evolutionary Processes

    International Nuclear Information System (INIS)

    Schuster, P.

    2010-01-01

    Darwin's principle of evolution by natural selection is readily casted into a mathematical formalism. Molecular biology revealed the mechanism of mutation and provides the basis for a kinetic theory of evolution that models correct reproduction and mutation as parallel chemical reaction channels. A result of the kinetic theory is the existence of a phase transition in evolution occurring at a critical mutation rate, which represents a localization threshold for the population in sequence space. Occurrence and nature of such phase transitions depend critically on fitness landscapes. The fitness landscape being tantamount to a mapping from sequence or genotype space into phenotype space is identified as the true source of complexity in evolution. Modeling evolution as a stochastic process is discussed and neutrality with respect to selection is shown to provide a major challenge for understanding evolutionary processes (author)

  4. Democratizing evolutionary biology, lessons from insects

    DEFF Research Database (Denmark)

    Dunn, Robert Roberdeau; Beasley, DeAnna E.

    2016-01-01

    The engagement of the public in the scientific process is an old practice. Yet with recent advances in technology, the role of the citizen scientist in studying evolutionary processes has increased. Insects provide ideal models for understanding these evolutionary processes at large scales. This ...

  5. Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK

    International Nuclear Information System (INIS)

    Fontana, Diletta; Ceccon, Monica; Gambacorti-Passerini, Carlo; Mologni, Luca

    2015-01-01

    Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors. About 80% of ALK-positive anaplastic large-cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)-ALK, whereas 5% of non-small-cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases. However, several cases of resistance appeared in NSCLC patients, and ALK amino acid substitutions were identified as a leading cause of resistance to crizotinib. Second-generation ALK inhibitors have been developed in order to overcome crizotinib resistance. In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs. Since the biological activity of ALK mutations extends beyond the specific type of fusion, both NPM-ALK- and EML4-ALK-positive cellular models were used. Our data revealed that most mutants may be targeted by using different inhibitors. One relevant exception is represented by the G1202R substitution, which was highly resistant to all drugs (>10-fold increased IC 50 compared to wild type) and may represent the most challenging mutation to overcome. These results provide a prediction of cross-resistance of known crizotinib-resistant mutations against all second-generation tyrosine kinase inhibitors (TKIs) clinically available, and therefore could be a useful tool to help clinicians in the management of crizotinib-resistance cases

  6. Vaccination with a HSV-2 UL24 mutant induces a protective immune response in murine and guinea pig vaginal infection models.

    Science.gov (United States)

    Visalli, Robert J; Natuk, Robert J; Kowalski, Jacek; Guo, Min; Blakeney, Susan; Gangolli, Seema; Cooper, David

    2014-03-10

    The rational design and development of genetically attenuated HSV-2 mutant viruses represent an attractive approach for developing both prophylactic and therapeutic vaccines for genital herpes. Previously, HSV-2 UL24 was shown to be a virulence determinant in both murine and guinea pig vaginal infection models. An UL24-βgluc insertion mutant produced syncytial plaques and replicated to nearly wild type levels in tissue culture, but induced little or no pathological effects in recipient mice or guinea pigs following vaginal infection. Here we report that immunization of mice or guinea pigs with high or low doses of UL24-βgluc elicited a highly protective immune response. UL24-βgluc immunization via the vaginal or intramuscular routes was demonstrated to protect mice from a lethal vaginal challenge with wild type HSV-2. Moreover, antigen re-stimulated splenic lymphocytes harvested from immunized mice exhibited both HSV-2 specific CTL activity and IFN-γ expression. Humoral anti-HSV-2 responses in serum were Th1-polarized (IgG2a>IgG1) and contained high-titer anti-HSV-2 neutralizing activity. Guinea pigs vaccinated subcutaneously with UL24-βgluc or the more virulent parental strain (186) were challenged with a heterologous HSV-2 strain (MS). Acute disease scores were nearly indistinguishable in guinea pigs immunized with either virus. Recurrent disease scores were reduced in UL24-βgluc immunized animals but not to the same extent as those immunized with strain 186. In addition, challenge virus was not detected in 75% of guinea pigs subcutaneously immunized with UL24-βgluc. In conclusion, disruption of the UL24 gene is a prime target for the development of a genetically attenuated live HSV-2 vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Models for the a subunits of the Thermus thermophilus V/A-ATPase and Saccharomyces cerevisiae V-ATPase enzymes by cryo-EM and evolutionary covariance

    Science.gov (United States)

    Schep, Daniel G.; Rubinstein, John L.

    2016-01-01

    Rotary ATPases couple ATP synthesis or hydrolysis to proton translocation across a membrane. However, understanding proton translocation has been hampered by a lack of structural information for the membrane-embedded a subunit. The V/A-ATPase from the eubacterium Thermus thermophilus is similar in structure to the eukaryotic V-ATPase but has a simpler subunit composition and functions in vivo to synthesize ATP rather than pump protons. We determined the T. thermophilus V/A-ATPase structure by cryo-EM at 6.4 Å resolution. Evolutionary covariance analysis allowed tracing of the a subunit sequence within the map, providing a complete model of the rotary ATPase. Comparing the membrane-embedded regions of the T. thermophilus V/A-ATPase and eukaryotic V-ATPase from Saccharomyces cerevisiae allowed identification of the α-helices that belong to the a subunit and revealed the existence of previously unknown subunits in the eukaryotic enzyme. Subsequent evolutionary covariance analysis enabled construction of a model of the a subunit in the S. cerevisae V-ATPase that explains numerous biochemical studies of that enzyme. Comparing the two a subunit structures determined here with a structure of the distantly related a subunit from the bovine F-type ATP synthase revealed a conserved pattern of residues, suggesting a common mechanism for proton transport in all rotary ATPases. PMID:26951669

  8. Spore: Spawning Evolutionary Misconceptions?

    Science.gov (United States)

    Bean, Thomas E.; Sinatra, Gale M.; Schrader, P. G.

    2010-10-01

    The use of computer simulations as educational tools may afford the means to develop understanding of evolution as a natural, emergent, and decentralized process. However, special consideration of developmental constraints on learning may be necessary when using these technologies. Specifically, the essentialist (biological forms possess an immutable essence), teleological (assignment of purpose to living things and/or parts of living things that may not be purposeful), and intentionality (assumption that events are caused by an intelligent agent) biases may be reinforced through the use of computer simulations, rather than addressed with instruction. We examine the video game Spore for its depiction of evolutionary content and its potential to reinforce these cognitive biases. In particular, we discuss three pedagogical strategies to mitigate weaknesses of Spore and other computer simulations: directly targeting misconceptions through refutational approaches, targeting specific principles of scientific inquiry, and directly addressing issues related to models as cognitive tools.

  9. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

    Science.gov (United States)

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

    2016-11-01

    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Remembering the evolutionary Freud.

    Science.gov (United States)

    Young, Allan

    2006-03-01

    Throughout his career as a writer, Sigmund Freud maintained an interest in the evolutionary origins of the human mind and its neurotic and psychotic disorders. In common with many writers then and now, he believed that the evolutionary past is conserved in the mind and the brain. Today the "evolutionary Freud" is nearly forgotten. Even among Freudians, he is regarded to be a red herring, relevant only to the extent that he diverts attention from the enduring achievements of the authentic Freud. There are three ways to explain these attitudes. First, the evolutionary Freud's key work is the "Overview of the Transference Neurosis" (1915). But it was published at an inopportune moment, forty years after the author's death, during the so-called "Freud wars." Second, Freud eventually lost interest in the "Overview" and the prospect of a comprehensive evolutionary theory of psychopathology. The publication of The Ego and the Id (1923), introducing Freud's structural theory of the psyche, marked the point of no return. Finally, Freud's evolutionary theory is simply not credible. It is based on just-so stories and a thoroughly discredited evolutionary mechanism, Lamarckian use-inheritance. Explanations one and two are probably correct but also uninteresting. Explanation number three assumes that there is a fundamental difference between Freud's evolutionary narratives (not credible) and the evolutionary accounts of psychopathology that currently circulate in psychiatry and mainstream journals (credible). The assumption is mistaken but worth investigating.

  11. Productive mutants of niger

    International Nuclear Information System (INIS)

    Misra, R.C.

    2001-01-01

    Seeds of six niger (Guizotia abyssinica Cass.) varieties ('GA-10', 'ONS-8', 'IGP-72', 'N-71', 'NB-9' and 'UN-4') were treated with 0.5, 0.75 and 1% ethyl methanesulphonate. After four generations of selection, 29 mutant lines were developed and those were evaluated from 1990-92 during Kharif (July to October) and Rabi (December to March) seasons. Average plant characteristics and yield data of four high yielding mutants along with 'IGP-76' (National Check), GA-10 (Zonal Check) and 'Semiliguda Local' (Local Check) are presented

  12. Exponential Expansion in Evolutionary Economics

    DEFF Research Database (Denmark)

    Frederiksen, Peter; Jagtfelt, Tue

    2013-01-01

    This article attempts to solve current problems of conceptual fragmentation within the field of evolutionary economics. One of the problems, as noted by a number of observers, is that the field suffers from an assemblage of fragmented and scattered concepts (Boschma and Martin 2010). A solution...... to this problem is proposed in the form of a model of exponential expansion. The model outlines the overall structure and function of the economy as exponential expansion. The pictographic model describes four axiomatic concepts and their exponential nature. The interactive, directional, emerging and expanding...... concepts are described in detail. Taken together it provides the rudimentary aspects of an economic system within an analytical perspective. It is argued that the main dynamic processes of the evolutionary perspective can be reduced to these four concepts. The model and concepts are evaluated in the light...

  13. Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy

    OpenAIRE

    Freidl, Raphaela; Gstoettner, Antonia; Baranyi, Ulrike; Swoboda, Ines; Stolz, Frank; Focke-Tejkl, Margarete; Wekerle, Thomas; van Ree, Ronald; Valenta, Rudolf; Linhart, Birgit

    2016-01-01

    Background Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed. Objectives This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunizat...

  14. Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression.

    Science.gov (United States)

    Levit, Alexander; Regis, Aaron M; Garabon, Jessica R; Oh, Seung-Hun; Desai, Sagar J; Rajakumar, Nagalingam; Hachinski, Vladimir; Agca, Yuksel; Agca, Cansu; Whitehead, Shawn N; Allman, Brian L

    2017-08-30

    Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Cranial muscle development in the model organism ambystoma mexicanum: implications for tetrapod and vertebrate comparative and evolutionary morphology and notes on ontogeny and phylogeny.

    Science.gov (United States)

    Ziermann, Janine M; Diogo, Rui

    2013-07-01

    There is still confusion about the homology of several cranial muscles in salamanders with those of other vertebrates. This is true, in part, because of the fact that many muscles present in early ontogeny of amphibians disappear during development and specifically during metamorphosis. Resolving this confusion is important for the understanding of the comparative and evolutionary morphology of vertebrates and tetrapods because amphibians are the phylogenetically most plesiomorphic tetrapods, concerning for example their myology, and include two often used model organisms, Xenopus laevis (anuran) and Ambystoma mexicanum (urodele). Here we provide the first detailed report of the cranial muscle development in axolotl from early ontogenetic stages to the adult stage. We describe different and complementary types of general muscle morphogenetic gradients in the head: from anterior to posterior, from lateral to medial, and from origin to insertion. Furthermore, even during the development of neotenic salamanders such as axolotls, various larval muscles become indistinct, contradicting the commonly accepted view that during ontogeny the tendency is mostly toward the differentiation of muscles. We provide an updated comparison between these muscles and the muscles of other vertebrates, a discussion of the homologies and evolution, and show that the order in which the muscles appear during axolotl ontogeny is in general similar to their appearance in phylogeny (e.g. differentiation of adductor mandibulae muscles from one anlage to four muscles), with only a few remarkable exceptions, as for example the dilatator laryngis that appears evolutionary later but in the development before the intermandibularis. Copyright © 2013 Wiley Periodicals, Inc.

  16. Fixation times in evolutionary games under weak selection

    International Nuclear Information System (INIS)

    Altrock, Philipp M; Traulsen, Arne

    2009-01-01

    In evolutionary game dynamics, reproductive success increases with the performance in an evolutionary game. If strategy A performs better than strategy B, strategy A will spread in the population. Under stochastic dynamics, a single mutant will sooner or later take over the entire population or go extinct. We analyze the mean exit times (or average fixation times) associated with this process. We show analytically that these times depend on the payoff matrix of the game in an amazingly simple way under weak selection, i.e. strong stochasticity: the payoff difference Δπ is a linear function of the number of A individuals i, Δπ=u i+v. The unconditional mean exit time depends only on the constant term v. Given that a single A mutant takes over the population, the corresponding conditional mean exit time depends only on the density dependent term u. We demonstrate this finding for two commonly applied microscopic evolutionary processes.

  17. Chemical evolutionary games.

    Science.gov (United States)

    Aristotelous, Andreas C; Durrett, Richard

    2014-05-01

    Inspired by the use of hybrid cellular automata in modeling cancer, we introduce a generalization of evolutionary games in which cells produce and absorb chemicals, and the chemical concentrations dictate the death rates of cells and their fitnesses. Our long term aim is to understand how the details of the interactions in a system with n species and m chemicals translate into the qualitative behavior of the system. Here, we study two simple 2×2 games with two chemicals and revisit the two and three species versions of the one chemical colicin system studied earlier by Durrett and Levin (1997). We find that in the 2×2 examples, the behavior of our new spatial model can be predicted from that of the mean field differential equation using ideas of Durrett and Levin (1994). However, in the three species colicin model, the system with diffusion does not have the coexistence which occurs in the lattices model in which sites interact with only their nearest neighbors. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Attractive evolutionary equilibria

    OpenAIRE

    Roorda, Berend; Joosten, Reinoud

    2011-01-01

    We present attractiveness, a refinement criterion for evolutionary equilibria. Equilibria surviving this criterion are robust to small perturbations of the underlying payoff system or the dynamics at hand. Furthermore, certain attractive equilibria are equivalent to others for certain evolutionary dynamics. For instance, each attractive evolutionarily stable strategy is an attractive evolutionarily stable equilibrium for certain barycentric ray-projection dynamics, and vice versa.

  19. P01.29 Mutant (R132H) IDH1-driven cellular transformation makes cells dependent on continued wild type IDH1 expression in a model of in vitro gliomagenesis

    Science.gov (United States)

    Johannessen, T.; Mukherjee, J.; Wood, M.; Viswanath, P.; Ohba, S.; Ronen, S.; Berkvig, R.; Pieper, R.

    2017-01-01

    Abstract Introduction: Missense R132H mutations in the active site of isocitrate dehydrogenase 1 (IDH1) biologically and diagnostically distinguish low-grade gliomas and secondary glioblastomas from primary glioblastomas. IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of α-ketoglutarate (α-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. We recently showed (Mol Cancer Res 14: 976–983, 2016) that although mutant IDH1 expression in hTERT-immortalized, p53/pRb-deficient astrocytes can drive cellular transformation and gliomagenesis, selective pharmacologic inhibition and elimination of 2-HG by the mutant IDH1 inhibitor AGI-5198 has little effect on the growth or clonagenicity of these transformed cells. To address the possible role of WT IDH1 in the growth of mutant IDH-driven tumor cells, we used a slightly different gliomagenesis model in which the transformation of TERT-deficient, p53/pRb-deficient astrocytes (pre-crisis cells) occurs only after prolonged expression of mutant IDH and passage through cellular crisis (post-crisis cells, Cancer Res 76:6680–6689, 2016). METHODS AND MATERIALS: Using this system we introduced AGI-5198, or siRNA targeting both WT and mutant forms of IDH1 into p53/pRb-deficient, mutant IDH1-expressing human astrocytes prior to or following their transformation, and compared the effects on cell growth and clonagenicity. Results: AGI-5198 exposure decreased levels of 2HG by greater than 90%, and as previously reported had no effect on the growth of either the pre-or post-crisis cell populations. A one-day exposure to a pan IDH1 siRNA resulted in a similar, prolonged (greater than 6 day), 80% inhibition of both WT and mutant IDH1 protein levels and 2HG in both cell groups. While the growth of the mutant IDH-expressing, non-transformed cells was similar to that of scramble siRNA controls, the growth

  20. Clinical responses to ERK inhibition in BRAFV600E-mutant colorectal cancer predicted using a computational model.

    Science.gov (United States)

    Kirouac, Daniel C; Schaefer, Gabriele; Chan, Jocelyn; Merchant, Mark; Orr, Christine; Huang, Shih-Min A; Moffat, John; Liu, Lichuan; Gadkar, Kapil; Ramanujan, Saroja

    2017-01-01

    Approximately 10% of colorectal cancers harbor BRAF V600E mutations, which constitutively activate the MAPK signaling pathway. We sought to determine whether ERK inhibitor (GDC-0994)-containing regimens may be of clinical benefit to these patients based on data from in vitro (cell line) and in vivo (cell- and patient-derived xenograft) studies of cetuximab (EGFR), vemurafenib (BRAF), cobimetinib (MEK), and GDC-0994 (ERK) combinations. Preclinical data was used to develop a mechanism-based computational model linking cell surface receptor (EGFR) activation, the MAPK signaling pathway, and tumor growth. Clinical predictions of anti-tumor activity were enabled by the use of tumor response data from three Phase 1 clinical trials testing combinations of EGFR, BRAF, and MEK inhibitors. Simulated responses to GDC-0994 monotherapy (overall response rate = 17%) accurately predicted results from a Phase 1 clinical trial regarding the number of responding patients (2/18) and the distribution of tumor size changes ("waterfall plot"). Prospective simulations were then used to evaluate potential drug combinations and predictive biomarkers for increasing responsiveness to MEK/ERK inhibitors in these patients.

  1. Maternal Supply of Cas9 to Zygotes Facilitates the Efficient Generation of Site-Specific Mutant Mouse Models

    Science.gov (United States)

    Cebrian-Serrano, Alberto; Zha, Shijun; Hanssen, Lars; Biggs, Daniel; Preece, Christopher

    2017-01-01

    Genome manipulation in the mouse via microinjection of CRISPR/Cas9 site-specific nucleases has allowed the production time for genetically modified mouse models to be significantly reduced. Successful genome manipulation in the mouse has already been reported using Cas9 supplied by microinjection of a DNA construct, in vitro transcribed mRNA and recombinant protein. Recently the use of transgenic strains of mice overexpressing Cas9 has been shown to facilitate site-specific mutagenesis via maternal supply to zygotes and this route may provide an alternative to exogenous supply. We have investigated the feasibility of supplying Cas9 genetically in more detail and for this purpose we report the generation of a transgenic mice which overexpress Cas9 ubiquitously, via a CAG-Cas9 transgene targeted to the Gt(ROSA26)Sor locus. We show that zygotes prepared from female mice harbouring this transgene are sufficiently loaded with maternally contributed Cas9 for efficient production of embryos and mice harbouring indel, genomic deletion and knock-in alleles by microinjection of guide RNAs and templates alone. We compare the mutagenesis rates and efficacy of mutagenesis using this genetic supply with exogenous Cas9 supply by either mRNA or protein microinjection. In general, we report increased generation rates of knock-in alleles and show that the levels of mutagenesis at certain genome target sites are significantly higher and more consistent when Cas9 is supplied genetically relative to exogenous supply. PMID:28081254

  2. Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases

    OpenAIRE

    Adnan, Humaira; Zhang, Zhenbo; Park, Hyun-Joo; Tailor, Chetankumar; Che, Clare; Kamani, Mustafa; Spitalny, George; Binnington, Beth; Lingwood, Clifford

    2016-01-01

    Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subu...

  3. Genomic Sequencing of Japanese Plum (Prunus salicina Lindl. Mutants Provides a New Model for Rosaceae Fruit Ripening Studies

    Directory of Open Access Journals (Sweden)

    Angel Fernandez i Marti

    2018-02-01

    Full Text Available It has recently been described that the Japanese plum “Santa Rosa” bud sport series contains variations in ripening pattern: climacteric, suppressed-climacteric and non-climacteric types. This provides an interesting model to study the role of ethylene and other key mechanisms governing fruit ripening, softening and senescence. The aim of the current study was to investigate such differences at the genomic level, using this series of plum bud sports, with special reference to genes involved in ethylene biosynthesis, signal transduction, and sugar metabolism. Genomic DNA, isolated from leaf samples of six Japanese plum cultivars (“Santa Rosa”, “July Santa Rosa”, “Late Santa Rosa”, “Sweet Miriam”, “Roysum”, and “Casselman”, was used to construct paired-end standard Illumina libraries. Sequences were aligned to the Prunus persica genome, and genomic variations (SNPs, INDELS, and CNV's were investigated. Results determined 12 potential candidate genes with significant copy number variation (CNV, being associated with ethylene perception and signal transduction components. Additionally, the Maximum Likelihood (ML phylogenetic tree showed two sorbitol dehydrogenase genes grouping into a distinct clade, indicating that this natural group is well-defined and presents high sequence identity among its members. In contrast, the ethylene group, which includes ACO1, ACS1, ACS4, ACS5, CTR1, ERF1, ERF3, and ethylene-receptor genes, was widely distributed and clustered into 10 different groups. Thus, ACS, ERF, and sorbitol dehydrogenase proteins potentially share a common ancestor for different plant genomes, while the expansion rate may be related to ancestral expansion rather than species-specific events. Based on the distribution of the clades, we suggest that gene function diversification for the ripening pathway occurred prior to family extension. We herein report all the frameshift mutations in genes involved in sugar transport

  4. Genomic Sequencing of Japanese Plum (Prunus salicina Lindl.) Mutants Provides a New Model for Rosaceae Fruit Ripening Studies.

    Science.gov (United States)

    Fernandez I Marti, Angel; Saski, Christopher A; Manganaris, George A; Gasic, Ksenija; Crisosto, Carlos H

    2018-01-01

    It has recently been described that the Japanese plum "Santa Rosa" bud sport series contains variations in ripening pattern: climacteric, suppressed-climacteric and non-climacteric types. This provides an interesting model to study the role of ethylene and other key mechanisms governing fruit ripening, softening and senescence. The aim of the current study was to investigate such differences at the genomic level, using this series of plum bud sports, with special reference to genes involved in ethylene biosynthesis, signal transduction, and sugar metabolism. Genomic DNA, isolated from leaf samples of six Japanese plum cultivars ("Santa Rosa", "July Santa Rosa", "Late Santa Rosa", "Sweet Miriam", "Roysum", and "Casselman"), was used to construct paired-end standard Illumina libraries. Sequences were aligned to the Prunus persica genome, and genomic variations (SNPs, INDELS, and CNV's) were investigated. Results determined 12 potential candidate genes with significant copy number variation (CNV), being associated with ethylene perception and signal transduction components. Additionally, the Maximum Likelihood (ML) phylogenetic tree showed two sorbitol dehydrogenase genes grouping into a distinct clade, indicating that this natural group is well-defined and presents high sequence identity among its members. In contrast, the ethylene group, which includes ACO1, ACS1, ACS4, ACS5, CTR1, ERF1, ERF3, and ethylene-receptor genes, was widely distributed and clustered into 10 different groups. Thus, ACS, ERF, and sorbitol dehydrogenase proteins potentially share a common ancestor for different plant genomes, while the expansion rate may be related to ancestral expansion rather than species-specific events. Based on the distribution of the clades, we suggest that gene function diversification for the ripening pathway occurred prior to family extension. We herein report all the frameshift mutations in genes involved in sugar transport and ethylene biosynthesis detected as well

  5. An inducer of VGF protects cells against ER stress-induced cell death and prolongs survival in the mutant SOD1 animal models of familial ALS.

    Directory of Open Access Journals (Sweden)

    Masamitsu Shimazawa

    2010-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most frequent adult-onset motor neuron disease, and recent evidence has suggested that endoplasmic reticulum (ER stress signaling is involved in the pathogenesis of ALS. Here we identified a small molecule, SUN N8075, which has a marked protective effect on ER stress-induced cell death, in an in vitro cell-based screening, and its protective mechanism was mediated by an induction of VGF nerve growth factor inducible (VGF: VGF knockdown with siRNA completely abolished the protective effect of SUN N8075 against ER-induced cell death, and overexpression of VGF inhibited ER-stress-induced cell death. VGF level was lower in the spinal cords of sporadic ALS patients than in the control patients. Furthermore, SUN N8075 slowed disease progression and prolonged survival in mutant SOD1 transgenic mouse and rat models of ALS, preventing the decrease of VGF expression in the spinal cords of ALS mice. These data suggest that VGF plays a critical role in motor neuron survival and may be a potential new therapeutic target for ALS, and SUN N8075 may become a potential therapeutic candidate for treatment of ALS.

  6. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

    International Nuclear Information System (INIS)

    Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

    2012-01-01

    Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  7. From discovery of high lysine barley endosperm mutants in the 1960-70 ties to new holistic spectral models of the phenome and of pleiotropy in 2008

    International Nuclear Information System (INIS)

    Munck, L.; Moeller Jespersen, B.

    2008-01-01

    As documented by eight IAEA/FAO symposia 1968-82 on nutritionally improved seeds, a wide range of high lysine endosperm mutants were isolated in maize, sorghum and barley. These mutants observed by new spectroscopic screening methods can now be exploited to advance basic biological research and theory. Since 1982 effective methods to overview the physiochemical composition of seeds by Near Infrared Spectroscopy evaluated by chemometric data analysis have developed. Spectroscopic analyses by calibration have now substituted for the wet analyses in industry. In genetics there has traditionally been a differentiation between major genes for qualitative and minor 'polygenes' for quantitative traits. This view has been coupled to an incomplete understanding of pleiotropy. It is shown that seed spectra from isogenic barley endosperm mutants represent a coarse-grained physiochemical overview of the phenome that can be classified by chemometrics. Pleiotropy expressed by a gene is quantified as a whole pattern by the gene specific mutant spectrum subtracted by the spectrum of the parent variety. Selection for an improved plumpness (starch) in a breeding material with the lys3.a mutant visualises in spectra the effect of enriching 'minor polygenes' for an increased content of starch in a mutant gene background. Morphological, spectroscopic and chemical analyses suggest that mutant genes have both qualitative and quantitative expressions. They produce qualitative pleiotropic phenomenological patterns that can be observed as more or less severe changes in macro and microstructures of the plant and seed phenotype. Behind are quantitative chemical changes that by spectroscopy and chemometrics can be transferred to qualitative patterns. In fact one major gene for a qualitative trait can act as several apparent minor polygenes for quantitative variables. This explains the reduced need for the previously expected several hundred thousands of genes and gene modifiers down to the

  8. Modeling and Docking Studies on Novel Mutants (K71L and T204V of the ATPase Domain of Human Heat Shock 70 kDa Protein 1

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    Asita Elengoe

    2014-04-01

    Full Text Available The purpose of exploring protein interactions between human adenovirus and heat shock protein 70 is to exploit a potentially synergistic interaction to enhance anti-tumoral efficacy and decrease toxicity in cancer treatment. However, the protein interaction of Hsp70 with E1A32 kDa of human adenovirus serotype 5 remains to be elucidated. In this study, two residues of ATPase domain of human heat shock 70 kDa protein 1 (PDB: 1 HJO were mutated. 3D mutant models (K71L and T204V using PyMol software were then constructed. The structures were evaluated by PROCHECK, ProQ, ERRAT, Verify 3D and ProSA modules. All evidence suggests that all protein models are acceptable and of good quality. The E1A32 kDa motif was retrieved from UniProt (P03255, as well as subjected to docking interaction with NBD, K71L and T204V, using the Autodock 4.2 program. The best lowest binding energy value of −9.09 kcal/mol was selected for novel T204V. Moreover, the protein-ligand complex structures were validated by RMSD, RMSF, hydrogen bonds and salt bridge analysis. This revealed that the T204V-E1A32 kDa motif complex was the most stable among all three complex structures. This study provides information about the interaction between Hsp70 and the E1A32 kDa motif, which emphasizes future perspectives to design rational drugs and vaccines in cancer therapy.

  9. Connexin mutants and cataracts

    Directory of Open Access Journals (Sweden)

    Eric C Beyer

    2013-04-01

    Full Text Available The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8 have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death and formation of cytoplasmic accumulations (that may act as light scattering particles. These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues.

  10. Evolutionary algorithms for mobile ad hoc networks

    CERN Document Server

    Dorronsoro, Bernabé; Danoy, Grégoire; Pigné, Yoann; Bouvry, Pascal

    2014-01-01

    Describes how evolutionary algorithms (EAs) can be used to identify, model, and minimize day-to-day problems that arise for researchers in optimization and mobile networking. Mobile ad hoc networks (MANETs), vehicular networks (VANETs), sensor networks (SNs), and hybrid networks—each of these require a designer’s keen sense and knowledge of evolutionary algorithms in order to help with the common issues that plague professionals involved in optimization and mobile networking. This book introduces readers to both mobile ad hoc networks and evolutionary algorithms, presenting basic concepts as well as detailed descriptions of each. It demonstrates how metaheuristics and evolutionary algorithms (EAs) can be used to help provide low-cost operations in the optimization process—allowing designers to put some “intelligence” or sophistication into the design. It also offers efficient and accurate information on dissemination algorithms topology management, and mobility models to address challenges in the ...

  11. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... ... of events: 'Entities that were capable of independent replication ... There have been many major evolutionary events that this definition of .... selection at level x to exclusive selection at x – will probably require a multiplicity ...

  12. Evolutionary relationships among Astroviridae

    NARCIS (Netherlands)

    Lukashov, Vladimir V.; Goudsmit, Jaap

    2002-01-01

    To study the evolutionary relationships among astroviruses, all available sequences for members of the family Astroviridae were collected. Phylogenetic analysis distinguished two deep-rooted groups: one comprising mammalian astroviruses, with ovine astrovirus being an outlier, and the other

  13. Multidimensional extended spatial evolutionary games.

    Science.gov (United States)

    Krześlak, Michał; Świerniak, Andrzej

    2016-02-01

    The goal of this paper is to study the classical hawk-dove model using mixed spatial evolutionary games (MSEG). In these games, played on a lattice, an additional spatial layer is introduced for dependence on more complex parameters and simulation of changes in the environment. Furthermore, diverse polymorphic equilibrium points dependent on cell reproduction, model parameters, and their simulation are discussed. Our analysis demonstrates the sensitivity properties of MSEGs and possibilities for further development. We discuss applications of MSEGs, particularly algorithms for modelling cell interactions during the development of tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  15. Evolutionary Multiplayer Games

    OpenAIRE

    Gokhale, Chaitanya S.; Traulsen, Arne

    2014-01-01

    Evolutionary game theory has become one of the most diverse and far reaching theories in biology. Applications of this theory range from cell dynamics to social evolution. However, many applications make it clear that inherent non-linearities of natural systems need to be taken into account. One way of introducing such non-linearities into evolutionary games is by the inclusion of multiple players. An example is of social dilemmas, where group benefits could e.g.\\ increase less than linear wi...

  16. Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

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    Seok Joo Park

    2014-09-01

    Full Text Available BackgroundIt has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH/insulin-like growth factor-1 (IGF-1.MethodsIn this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice.ResultsThe GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt/phospho-glycogen synthase kinase3β (p-GSK3β, phospho-extracellular signal-related kinase (p-ERK, and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK, Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist.ConclusionThe results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

  17. Phylogenetic inference with weighted codon evolutionary distances.

    Science.gov (United States)

    Criscuolo, Alexis; Michel, Christian J

    2009-04-01

    We develop a new approach to estimate a matrix of pairwise evolutionary distances from a codon-based alignment based on a codon evolutionary model. The method first computes a standard distance matrix for each of the three codon positions. Then these three distance matrices are weighted according to an estimate of the global evolutionary rate of each codon position and averaged into a unique distance matrix. Using a large set of both real and simulated codon-based alignments of nucleotide sequences, we show that this approach leads to distance matrices that have a significantly better treelikeness compared to those obtained by standard nucleotide evolutionary distances. We also propose an alternative weighting to eliminate the part of the noise often associated with some codon positions, particularly the third position, which is known to induce a fast evolutionary rate. Simulation results show that fast distance-based tree reconstruction algorithms on distance matrices based on this codon position weighting can lead to phylogenetic trees that are at least as accurate as, if not better, than those inferred by maximum likelihood. Finally, a well-known multigene dataset composed of eight yeast species and 106 codon-based alignments is reanalyzed and shows that our codon evolutionary distances allow building a phylogenetic tree which is similar to those obtained by non-distance-based methods (e.g., maximum parsimony and maximum likelihood) and also significantly improved compared to standard nucleotide evolutionary distance estimates.

  18. Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER-2 and Mutant RAS/RAF Breast Cancer Model Systems

    Directory of Open Access Journals (Sweden)

    Teddy S Nagaria

    2013-08-01

    Full Text Available Oncogenic receptor tyrosine kinase (RTK signaling through the Ras-Raf-Mek-Erk (Ras-MAPK pathway is implicated in a wide array of carcinomas, including those of the breast. The cyclin-dependent kinases (CDKs are implicated in regulating proliferative and survival signaling downstream of this pathway. Here, we show that CDK inhibitors exhibit an order of magnitude greater cytotoxic potency than a suite of inhibitors targeting RTK and Ras-MAPK signaling in cell lines representative of clinically recognized breast cancer (BC subtypes. Drug combination studies show that the pan-CDK inhibitor, flavopiridol (FPD, synergistically potentiated cytotoxicity induced by the Raf inhibitor, sorafenib (SFN. This synergy was most pronounced at sub-EC50 SFN concentrations in MDA-MB-231 (KRAS-G13D and BRAF-G464V mutations, MDA-MB-468 [epidermal growth factor receptor (EGFR overexpression], and SKBR3 [ErbB2/EGFR2 (HER-2 overexpression] cells but not in hormone-dependent MCF-7 and T47D cells. Potentiation of SFN cytotoxicity by FPD correlated with enhanced apoptosis, suppression of retinoblastoma (Rb signaling, and reduced Mcl-1 expression. SFN and FPD were also tested in an MDA-MB-231 mammary fat pad engraftment model of tumorigenesis. Mice treated with both drugs exhibited reduced primary tumor growth rates and metastatic tumor load in the lungs compared to treatment with either drug alone, and this correlated with greater reductions in Rb signaling and Mcl-1 expression in resected tumors. These findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant BCs.

  19. Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.

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    Nupur Dasgupta

    Full Text Available Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT with the biosimilars, imiglucerase (imig or velaglucerase alfa (vela improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq of no ERT and ERT (imig or vela were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray, and DESeq and edgeR (mRNA-Seq. While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs (∼3-fold than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT

  20. Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI).

    Science.gov (United States)

    Masuya, Hiroshi; Shimizu, Kunihiko; Sezutsu, Hideki; Sakuraba, Yoshiyuki; Nagano, Junko; Shimizu, Aya; Fujimoto, Naomi; Kawai, Akiko; Miura, Ikuo; Kaneda, Hideki; Kobayashi, Kimio; Ishijima, Junko; Maeda, Takahide; Gondo, Yoichi; Noda, Tetsuo; Wakana, Shigeharu; Shiroishi, Toshihiko

    2005-03-01

    Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.

  1. Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.

    Directory of Open Access Journals (Sweden)

    Tobias Sikosek

    2016-06-01

    Full Text Available Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein's folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-α and GB α+β folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic π-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches.

  2. Schroedinger operators and evolutionary strategies

    International Nuclear Information System (INIS)

    Asselmeyer, T.

    1997-01-01

    First we introduce a simple model for the description of evolutionary algorithms, which is based on 2nd order partial differential equations for the distribution function of the individuals. Then we turn to the properties of Boltzmann's and Darwin's strategy. the next chapter is dedicated to the mathematical properties of Schroedinger operators. Both statements on the spectral density and their reproducibility during the simulation are summarized. The remaining of this chapter are dedicated to the analysis of the kernel as well as the dependence of the Schroedinger operator on the potential. As conclusion from the results of this chapter we obtain the classification of the strategies in dependence of the fitness. We obtain the classification of the evolutionary strategies, which are described by a 2nd order partial differential equation, in relation to their solution behaviour. Thereafter we are employed with the variation of the mutation distribution

  3. Preventive evolutionary medicine of cancers.

    Science.gov (United States)

    Hochberg, Michael E; Thomas, Frédéric; Assenat, Eric; Hibner, Urszula

    2013-01-01

    Evolutionary theory predicts that once an individual reaches an age of sufficiently low Darwinian fitness, (s)he will have reduced chances of keeping cancerous lesions in check. While we clearly need to better understand the emergence of precursor states and early malignancies as well as their mitigation by the microenvironment and tissue architecture, we argue that lifestyle changes and preventive therapies based in an evolutionary framework, applied to identified high-risk populations before incipient neoplasms become clinically detectable and chemoresistant lineages emerge, are currently the most reliable way to control or eliminate early tumours. Specifically, the relatively low levels of (epi)genetic heterogeneity characteristic of many if not most incipient lesions will mean a relatively limited set of possible adaptive traits and associated costs compared to more advanced cancers, and thus a more complete and predictable understanding of treatment options and outcomes. We propose a conceptual model for preventive treatments and discuss the many associated challenges.

  4. Sequence co-evolutionary information is a natural partner to minimally-frustrated models of biomolecular dynamics [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Jeffrey K Noel

    2016-01-01

    Full Text Available Experimentally derived structural constraints have been crucial to the implementation of computational models of biomolecular dynamics. For example, not only does crystallography provide essential starting points for molecular simulations but also high-resolution structures permit for parameterization of simplified models. Since the energy landscapes for proteins and other biomolecules have been shown to be minimally frustrated and therefore funneled, these structure-based models have played a major role in understanding the mechanisms governing folding and many functions of these systems. Structural information, however, may be limited in many interesting cases. Recently, the statistical analysis of residue co-evolution in families of protein sequences has provided a complementary method of discovering residue-residue contact interactions involved in functional configurations. These functional configurations are often transient and difficult to capture experimentally. Thus, co-evolutionary information can be merged with that available for experimentally characterized low free-energy structures, in order to more fully capture the true underlying biomolecular energy landscape.

  5. Evolutionary programming as a platform for in silico metabolic engineering

    Directory of Open Access Journals (Sweden)

    Förster Jochen

    2005-12-01

    Full Text Available Abstract Background Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms where structural and stoichiometric complexity is inherently accounted for. New algorithms are being developed by using genome-scale metabolic models that enable identification of gene knockout strategies for obtaining improved phenotypes. However, the problem of finding optimal gene deletion strategy is combinatorial and consequently the computational time increases exponentially with the size of the problem, and it is therefore interesting to develop new faster algorithms. Results In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters in industrial fermentations, one linear and other non-linear, by using a genome-scale model of the yeast Saccharomyces cerevisiae. Potential metabolic engineering targets for improved production of succinic acid, glycerol and vanillin are identified and underlying flux changes for the predicted mutants are discussed. Conclusion We show that evolutionary programming enables solving large gene knockout problems in relatively short computational time. The proposed algorithm also allows the optimization of non-linear objective functions or incorporation of non-linear constraints and additionally provides a family of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span

  6. Determining the role of inflammation in the selection of JAK2 mutant cells in myeloproliferative neoplasms.

    Science.gov (United States)

    Zhang, Jie; Fleischman, Angela G; Wodarz, Dominik; Komarova, Natalia L

    2017-07-21

    Myeloproliferative neoplasm (MPN) is a hematologic malignancy characterized by the clonal outgrowth of hematopoietic cells with a somatically acquired mutation most commonly in JAK2 (JAK2 V617F ). This mutation endows upon myeloid progenitors cytokine independent growth and consequently leads to excessive production of myeloid lineage cells. It has been previously suggested that inflammation may play a role in the clonal evolution of JAK2 V617F mutants. In particular, it is possible that one or more cellular kinetic parameters of hematopoietic stem cells (HSCs) are affected by inflammation, such as division or death rates of cells, and the probability of HSC differentiation. This suggests a mechanism that can steer the outcome of the cellular competition in favor of the mutants, initiating the disease. In this paper we create a number of mathematical evolutionary models, from very abstract to more concrete, that describe cellular competition in the context of inflammation. It is possible to build a model axiomatically, where only very general assumptions are imposed on the modeling components and no arbitrary (and generally unknown) functional forms are used, and still generate a set of testable predictions. In particular, we show that, if HSC death is negligible, the evolutionary advantage of mutant cells can only be conferred by an increase in differentiation probability of HSCs in the presence of inflammation, and if death plays a significant role in the dynamics, an additional mechanism may be an increase of HSC's division-to-death ratio in the presence of inflammation. Further, we show that in the presence of inflammation, the wild type cell population is predicted to shrink under inflammation (even in the absence of mutants). Finally, it turns out that if only the differentiation probability is affected by the inflammation, then the resulting steady state population of wild type cells will contain a relatively smaller percentage of HSCs under inflammation. If

  7. The influence of deterministic and stochastic waiting time for triggering mortality and colonization events on the coexistence of cooperators and defectors in an evolutionary game model

    Directory of Open Access Journals (Sweden)

    YouHua Chen

    2014-06-01

    waiting time, both defectors and cooperators could coexist, regardless of the types of waiting time for colonization events. Defense (or cooperation rewards could determine the persistence time of both game players. When the defense reward is low, cooperators could persist better in the simulation. But when the defense reward becomes sufficiently higher, defectors would persist better. Overall, non-coexistence of cooperators and defectors in the present evolutionary game model is dependent on the stochastic mortality events, but not colonization events. In conclusion, my present study quantifies the influence of the temporally fluctuating motility-colonization dynamic on modeling the coexistence of species in the spatial evolutionary game.

  8. Modelling and multi-objective optimization of a variable valve-timing spark-ignition engine using polynomial neural networks and evolutionary algorithms

    International Nuclear Information System (INIS)

    Atashkari, K.; Nariman-Zadeh, N.; Goelcue, M.; Khalkhali, A.; Jamali, A.

    2007-01-01

    The main reason for the efficiency decrease at part load conditions for four-stroke spark-ignition (SI) engines is the flow restriction at the cross-sectional area of the intake system. Traditionally, valve-timing has been designed to optimize operation at high engine-speed and wide open throttle conditions. Several investigations have demonstrated that improvements at part load conditions in engine performance can be accomplished if the valve-timing is variable. Controlling valve-timing can be used to improve the torque and power curve as well as to reduce fuel consumption and emissions. In this paper, a group method of data handling (GMDH) type neural network and evolutionary algorithms (EAs) are firstly used for modelling the effects of intake valve-timing (V t ) and engine speed (N) of a spark-ignition engine on both developed engine torque (T) and fuel consumption (Fc) using some experimentally obtained training and test data. Using such obtained polynomial neural network models, a multi-objective EA (non-dominated sorting genetic algorithm, NSGA-II) with a new diversity preserving mechanism are secondly used for Pareto based optimization of the variable valve-timing engine considering two conflicting objectives such as torque (T) and fuel consumption (Fc). The comparison results demonstrate the superiority of the GMDH type models over feedforward neural network models in terms of the statistical measures in the training data, testing data and the number of hidden neurons. Further, it is shown that some interesting and important relationships, as useful optimal design principles, involved in the performance of the variable valve-timing four-stroke spark-ignition engine can be discovered by the Pareto based multi-objective optimization of the polynomial models. Such important optimal principles would not have been obtained without the use of both the GMDH type neural network modelling and the multi-objective Pareto optimization approach

  9. A Computationally-Efficient, Multi-Mechanism Based Framework for the Comprehensive Modeling of the Evolutionary Behavior of Shape Memory Alloys

    Science.gov (United States)

    Saleeb, Atef F.; Vaidyanathan, Raj

    2016-01-01

    The report summarizes the accomplishments made during the 4-year duration of the project. Here, the major emphasis is placed on the different tasks performed by the two research teams; i.e., the modeling activities by the University of Akron (UA) team and the experimental and neutron diffraction studies conducted by the University of Central Florida (UCF) team, during this 4-year period. Further technical details are given in the upcoming sections by UA and UCF for each of the milestones/years (together with the corresponding figures and captions).The project majorly involved the development, validation, and application of a general theoretical model that is capable of capturing the nonlinear hysteretic responses, including pseudoelasticity, shape memory effect, rate-dependency, multi-axiality, asymmetry in tension versus compression response of shape memory alloys. Among the targeted goals for the SMA model was its ability to account for the evolutionary character response (including transient and long term behavior under sustained cycles) for both conventional and high temperature (HT) SMAs, as well as being able to simulate some of the devices which exploit these unique material systems. This required extensive (uniaxial and multi-axial) experiments needed to guide us in calibrating and characterizing the model. Moreover, since the model is formulated on the theoretical notion of internal state variables (ISVs), neutron diffraction experiments were needed to establish the linkage between the micromechanical changes and these ISVs. In addition, the design of the model should allow easy implementation in large scale finite element application to study the behavior of devices making use of these SMA materials under different loading controls. Summary of the activities, progress/achievements made during this period is given below in details for the University of Akron and the University (Section 2.0) of Central Florida (Section 3.0).

  10. Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

    2014-06-04

    Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

  11. Split-Ring Springback Simulations with the Non-associated Flow Rule and Evolutionary Elastic-Plasticity Models

    Science.gov (United States)

    Lee, K. J.; Choi, Y.; Choi, H. J.; Lee, J. Y.; Lee, M. G.

    2018-06-01

    Finite element simulations and experiments for the split-ring test were conducted to investigate the effect of anisotropic constitutive models on the predictive capability of sheet springback. As an alternative to the commonly employed associated flow rule, a non-associated flow rule for Hill1948 yield function was implemented in the simulations. Moreover, the evolution of anisotropy with plastic deformation was efficiently modeled by identifying equivalent plastic strain-dependent anisotropic coefficients. Comparative study with different yield surfaces and elasticity models showed that the split-ring springback could be best predicted when the anisotropy in both the R value and yield stress, their evolution and variable apparent elastic modulus were taken into account in the simulations. Detailed analyses based on deformation paths superimposed on the anisotropic yield functions predicted by different constitutive models were provided to understand the complex springback response in the split-ring test.

  12. Characterization of a Weak Allele of Zebrafish cloche Mutant

    Science.gov (United States)

    Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

    2011-01-01

    Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

  13. Photorepair mutants of Arabidopsis

    International Nuclear Information System (INIS)

    Jiang, C.Z.; Yee, J.; Mitchell, D.L.; Britt, A.B.

    1997-01-01

    UV radiation induces two major DNA damage products, the cyclobutane pyrimidine dimer (CPD) and, at a lower frequency, the pyrimidine (6-4) pyrimidinone dimer (6-4 product). Although Escherichia coli and Saccharomyces cerevisiae produce a CPD-specific photolyase that eliminates only this class of dimer, Arabidopsis thaliana, Drosophila melanogaster, Crotalus atrox, and Xenopus laevis have recently been shown to photoreactivate both CPDs and 6-4 products. We describe the isolation and characterization of two new classes of mutants of Arabidopsis, termed uvr2 and uvr3, that are defective in the photoreactivation of CPDs and 6-4 products, respectively. We demonstrate that the CPD photolyase mutation is genetically linked to a DNA sequence encoding a type II (metazoan) CPD photolyase. In addition, we are able to generate plants in which only CPDs or 6-4 products are photoreactivated in the nuclear genome by exposing these mutants to UV light and then allowing them to repair one or the other class of dimers. This provides us with a unique opportunity to study the biological consequences of each of these two major UV-induced photoproducts in an intact living system

  14. Construindo Marcas Mutantes

    Directory of Open Access Journals (Sweden)

    Elizete De Azevedo Kreutz

    2012-09-01

    Full Text Available O presente artigo é o resultado de estudos realizados desde 2000 e busca instrumentalizar os proñssionals para a construção de Marcas Mutantes, que é   uma tendência contemporânea nas estratégias comunicacionais e de branding. Embora esta estratégia ainda não esteja consolidada, observamos que a mesma tem obtido um crescimento constante e tem sido adotadas pelas mais diferentes categorias de marcas e não apenas por aquelas direcionadas aos jovens, ao esporte, ao entretenimento, como era no principia. Com base na Hermenêutica de Profundidade de Thompson (1995, alicerçada nas pesquisas bibliográficas, de intemet, entrevistas e análise semiótica, desenhamos um método de construção de Marcas Mutantes dividido em sete fases. Como resultado, esperamos que este estudo possa auxiliar na compreensão dos processos envolvidos, ao mesmo tempo que provoque a discussão sobreo mesmo e, por consequência, o seu aprimoramento.

  15. Proteomics in evolutionary ecology.

    Science.gov (United States)

    Baer, B; Millar, A H

    2016-03-01

    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  16. Face Alignment Using Boosting and Evolutionary Search

    NARCIS (Netherlands)

    Zhang, Hua; Liu, Duanduan; Poel, Mannes; Nijholt, Antinus; Zha, H.; Taniguchi, R.-I.; Maybank, S.

    2010-01-01

    In this paper, we present a face alignment approach using granular features, boosting, and an evolutionary search algorithm. Active Appearance Models (AAM) integrate a shape-texture-combined morphable face model into an efficient fitting strategy, then Boosting Appearance Models (BAM) consider the

  17. Applying evolutionary anthropology.

    Science.gov (United States)

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. © 2015 Wiley Periodicals, Inc.

  18. Applying Evolutionary Anthropology

    Science.gov (United States)

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. PMID:25684561

  19. Evolutionary Modeling Predicts a Decrease in Postcopulatory Sperm Viability as a Response to Increasing Levels of Sperm Competition

    NARCIS (Netherlands)

    Engqvist, Leif

    Sperm competition has been found to have a strong influence on the evolution of many male and female reproductive traits. Theoretical models have shown that, with increasing levels of sperm competition, males are predicted to increase ejaculate investment, and there is ample empirical evidence

  20. Morphological and physiological investigations on mutants of Fusarium monoliforme IM

    International Nuclear Information System (INIS)

    Gancheva, V.

    1996-01-01

    High-producing mutants of Fusarium moniliforme IM are obtained as a result of gamma irradiation. The cultural characteristics of mutant strains 3284, 3211 and 76 following incubation of the producers for 14 days on potato-glucose agar are described. The colour of the aerial and substrate mycelium and the ability of the mutant strains to form conidiae and pigments are discussed in detail. The differences in the ability of mutants to assimilate different carbon and nitrogen sources are of specific importance for modelling nutrient media for submerged cultivation of F. moniliforme. 2 tabs., 2 figs. 7 refs

  1. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  2. Reproduction of a new inferior vena cava thrombosis model and study of the evolutionary process of thrombolysis in rats

    Directory of Open Access Journals (Sweden)

    Jian FU

    2015-10-01

    Full Text Available Objective To investigate the reproduction of a new model of thrombosis of inferior vena cava (IVC, and explore the natural process of thrombolysis and its mechanism in rats. Methods Forty-eight SD rats were randomly classified into experimental group and control group. In the experimental group, the lumen of the vena cava was blocked by about 80%-90% with a ligature of IVC below the left renal vein, and then the animals were redivided into three subgroups (n=12, each. In group A, the IVC endothelium was damaged and its tributaries were ligated. In group B, the IVC endothelium was damaged and its tributaries were not ligated. In group C, no damage was done to the endothelium of the IVC but all its tributaries were ligated. A sham-operated group served as control. The length and weight of the vinous thrombus and the percentage of the IVC luminal area were compared after operation to determine the optimum animal model of venous thrombosis. According to the best mode to establish the model, the thrombus specimens were collected and detected by HE and Masson staining, and the ED-1 expressions were examined by immunohistochemical staining after thrombus formation in 30 rats. The natural evolution of intravenous thrombolysis was analyzed dynamically and the cell types involved in this process were observed. Results Gross observation showed that the experimental group was successfully induced thrombus formation. The thrombus length and weight in group A was significantly higher than that in group B and group C, and no difference between group B and C. The thrombus area in group A was significantly higher than that in groups B and group C, which identified the group A was the optimal model group of venous thrombosis. In the group reproduced by the best mode of the model, HE and Masson staining results showed that new capillaries and the components of collagen and extracellular matrix increased gradually with the passage of time in the process of

  3. Quantitative RNA-Seq analysis in non-model species: assessing transcriptome assemblies as a scaffold and the utility of evolutionary divergent genomic reference species

    Directory of Open Access Journals (Sweden)

    Hornett Emily A

    2012-08-01

    Full Text Available Abstract Background How well does RNA-Seq data perform for quantitative whole gene expression analysis in the absence of a genome? This is one unanswered question facing the rapidly growing number of researchers studying non-model species. Using Homo sapiens data and resources, we compared the direct mapping of sequencing reads to predicted genes from the genome with mapping to de novo transcriptomes assembled from RNA-Seq data. Gene coverage and expression analysis was further investigated in the non-model context by using increasingly divergent genomic reference species to group assembled contigs by unique genes. Results Eight transcriptome sets, composed of varying amounts of Illumina and 454 data, were assembled and assessed. Hybrid 454/Illumina assemblies had the highest transcriptome and individual gene coverage. Quantitative whole gene expression levels were highly similar between using a de novo hybrid assembly and the predicted genes as a scaffold, although mapping to the de novo transcriptome assembly provided data on fewer genes. Using non-target species as reference scaffolds does result in some loss of sequence and expression data, and bias and error increase with evolutionary distance. However, within a 100 million year window these effect sizes are relatively small. Conclusions Predicted gene sets from sequenced genomes of related species can provide a powerful method for grouping RNA-Seq reads and annotating contigs. Gene expression results can be produced that are similar to results obtained using gene models derived from a high quality genome, though biased towards conserved genes. Our results demonstrate the power and limitations of conducting RNA-Seq in non-model species.

  4. The incommensurability of nursing as a practice and the customer service model: an evolutionary threat to the discipline.

    Science.gov (United States)

    Austin, Wendy J

    2011-07-01

    Corporate and commercial values are inducing some healthcare organizations to prescribe a customer service model that reframes the provision of nursing care. In this paper it is argued that such a model is incommensurable with nursing conceived as a moral practice and ultimately places nurses at risk. Based upon understanding from ongoing research on compassion fatigue, it is proposed that compassion fatigue as currently experienced by nurses may not arise predominantly from too great a demand for compassion, but rather from barriers to enacting compassionate care. These barriers are often systemic. The paradigm shift in which healthcare environments are viewed as marketplaces rather than moral communities has the potential to radically affect the evolution of nursing as a discipline. © 2011 Blackwell Publishing Ltd.

  5. Evolutionary Models of Red Supergiants: Evidence for A Metallicity-dependent Mixing Length and Implications for Type IIP Supernova Progenitors

    Science.gov (United States)

    Chun, Sang-Hyun; Yoon, Sung-Chul; Jung, Moo-Keon; Kim, Dong Uk; Kim, Jihoon

    2018-01-01

    Recent studies on the temperatures of red supergiants (RSGs) in the local universe provide us with an excellent observational constraint on RSG models. We calibrate the mixing length parameter by comparing model predictions with the empirical RSG temperatures in Small and Large Magellanic Clouds, Milky Way, and M31, which are inferred from the TiO band and the spectral energy distribution (SED). Although our RSG models are computed with the MESA code, our result may be applied to other stellar evolution codes, including the BEC and TWIN codes. We find evidence that the mixing length increases with increasing metallicity for both cases where the TiO and SED temperatures of RSGs are used for the calibration. Together with the recent finding of a similar correlation in low-mass red giants by Tayar et al., this implies that the metallicity dependence of the mixing length is a universal feature in post-main sequence stars of both low and high masses. Our result implies that typical Type IIP supernova (SN IIP) progenitors with initial masses of ∼ 10{--}16 {M}ȯ have a radius range of 400 {R}ȯ ≲ R≲ 800 {R}ȯ regardless of metallicity. As an auxiliary result of this study, we find that the hydrogen-rich envelope mass of SN IIP progenitors for a given initial mass is predicted to be largely independent of metallicity if the Ledoux criterion with slow semiconvection is adopted, while the Schwarzschild models predict systematically more massive hydrogen-rich envelopes for lower metallicity.

  6. Modelling formation of disinfection by-products in water distribution: Optimisation using a multi-objective evolutionary algorithm

    KAUST Repository

    Radhakrishnan, Mohanasundar; Pathirana, Assela; Ghebremichael, Kebreab A.; Amy, Gary L.

    2012-01-01

    Concerns have been raised regarding disinfection by-products (DBPs) formed as a result of the reaction of halogen-based disinfectants with DBP precursors. In order to appreciate the chemical and biological tradeoffs, it is imperative to understand the formation trends of DBPs and their spread in the distribution network. However, the water at a point in a complex distribution system is a mixture from various sources, whose proportions are complex to estimate and requires advanced hydraulic analysis. To understand the risks of DBPs and to develop mitigation strategies, it is important to understand the distribution of DBPs in a water network, which requires modelling. The goal of this research was to integrate a steady-state water network model with a particle backtracking algorithm and chlorination as well as DBPs models in order to assess the tradeoffs between biological and chemical risks in the distribution network. A multi-objective optimisation algorithm was used to identify the optimal proportion of water from various sources, dosages of alum, and dosages of chlorine in the treatment plant and in booster locations to control the formation of chlorination DBPs and to achieve a balance between microbial and chemical risks. © IWA Publishing 2012.

  7. Modelling formation of disinfection by-products in water distribution: Optimisation using a multi-objective evolutionary algorithm

    KAUST Repository

    Radhakrishnan, Mohanasundar

    2012-05-01

    Concerns have been raised regarding disinfection by-products (DBPs) formed as a result of the reaction of halogen-based disinfectants with DBP precursors. In order to appreciate the chemical and biological tradeoffs, it is imperative to understand the formation trends of DBPs and their spread in the distribution network. However, the water at a point in a complex distribution system is a mixture from various sources, whose proportions are complex to estimate and requires advanced hydraulic analysis. To understand the risks of DBPs and to develop mitigation strategies, it is important to understand the distribution of DBPs in a water network, which requires modelling. The goal of this research was to integrate a steady-state water network model with a particle backtracking algorithm and chlorination as well as DBPs models in order to assess the tradeoffs between biological and chemical risks in the distribution network. A multi-objective optimisation algorithm was used to identify the optimal proportion of water from various sources, dosages of alum, and dosages of chlorine in the treatment plant and in booster locations to control the formation of chlorination DBPs and to achieve a balance between microbial and chemical risks. © IWA Publishing 2012.

  8. Archaeogenetics in evolutionary medicine.

    Science.gov (United States)

    Bouwman, Abigail; Rühli, Frank

    2016-09-01

    Archaeogenetics is the study of exploration of ancient DNA (aDNA) of more than 70 years old. It is an important part of the wider studies of many different areas of our past, including animal, plant and pathogen evolution and domestication events. Hereby, we address specifically the impact of research in archaeogenetics in the broader field of evolutionary medicine. Studies on ancient hominid genomes help to understand even modern health patterns. Human genetic microevolution, e.g. related to abilities of post-weaning milk consumption, and specifically genetic adaptation in disease susceptibility, e.g. towards malaria and other infectious diseases, are of the upmost importance in contributions of archeogenetics on the evolutionary understanding of human health and disease. With the increase in both the understanding of modern medical genetics and the ability to deep sequence ancient genetic information, the field of archaeogenetic evolutionary medicine is blossoming.

  9. Part E: Evolutionary Computation

    DEFF Research Database (Denmark)

    2015-01-01

    of Computational Intelligence. First, comprehensive surveys of genetic algorithms, genetic programming, evolution strategies, parallel evolutionary algorithms are presented, which are readable and constructive so that a large audience might find them useful and – to some extent – ready to use. Some more general...... kinds of evolutionary algorithms, have been prudently analyzed. This analysis was followed by a thorough analysis of various issues involved in stochastic local search algorithms. An interesting survey of various technological and industrial applications in mechanical engineering and design has been...... topics like the estimation of distribution algorithms, indicator-based selection, etc., are also discussed. An important problem, from a theoretical and practical point of view, of learning classifier systems is presented in depth. Multiobjective evolutionary algorithms, which constitute one of the most...

  10. In Silico Molecular Modeling and Docking Studies on Novel Mutants (E229V, H225P and D230C) of the Nucleotide-Binding Domain of Homo sapiens Hsp70.

    Science.gov (United States)

    Elengoe, Asita; Hamdan, Salehhuddin

    2017-12-01

    In this study, we explored the possibility of determining the synergistic interactions between nucleotide-binding domain (NBD) of Homo sapiens heat-shock 70 kDa protein (Hsp70) and E1A 32 kDa of adenovirus serotype 5 motif (PNLVP) in the efficiency of killing of tumor cells in cancer treatment. At present, the protein interaction between NBD and PNLVP motif is still unknown, but believed to enhance the rate of virus replication in tumor cells. Three mutant models (E229V, H225P and D230C) were built and simulated, and their interactions with PNLVP motif were studied. The PNLVP motif showed the binding energy and intermolecular energy values with the novel E229V mutant at -7.32 and -11.2 kcal/mol. The E229V mutant had the highest number of hydrogen bonds (7). Based on the root mean square deviation, root mean square fluctuation, hydrogen bonds, salt bridge, secondary structure, surface-accessible solvent area, potential energy and distance matrices analyses, it was proved that the E229V had the strongest and most stable interaction with the PNLVP motif among all the four protein-ligand complex structures. The knowledge of this protein-ligand complex model would help in designing Hsp70 structure-based drug for cancer therapy.

  11. Isozyme differences in barley mutants

    Energy Technology Data Exchange (ETDEWEB)

    AI-Jibouri, A A.M.; Dham, K M [Department of Botany, Nuclear Research Centre, Baghdad (Iraq)

    1990-01-01

    Full text: Thirty mutants (M{sub 11}) of barley (Hordeum vulgare L.) induced by physical and chemical mutagens were analysed for isozyme composition using polyacrylamide gel electrophoresis. Results show that these mutants were different in the isozymes leucine aminopeptidase, esterase and peroxidase. The differences included the number of forms of each enzyme, relative mobility value and their intensity on the gel. Glutamate oxaloacetate transaminase isozyme was found in six molecular forms and these forms were similar in all mutants. (author)

  12. Isozyme differences in barley mutants

    International Nuclear Information System (INIS)

    AI-Jibouri, A.A.M.; Dham, K.M.

    1990-01-01

    Full text: Thirty mutants (M 11 ) of barley (Hordeum vulgare L.) induced by physical and chemical mutagens were analysed for isozyme composition using polyacrylamide gel electrophoresis. Results show that these mutants were different in the isozymes leucine aminopeptidase, esterase and peroxidase. The differences included the number of forms of each enzyme, relative mobility value and their intensity on the gel. Glutamate oxaloacetate transaminase isozyme was found in six molecular forms and these forms were similar in all mutants. (author)

  13. Relative size of the eye and orbit: an evolutionary and craniofacial constraint model for examining the etiology and disparate incidence of juvenile-onset myopia in humans.

    Science.gov (United States)

    Masters, Michael P

    2012-05-01

    The principal aim of this research is to provide a new model for investigating myopia in humans, and contribute to an understanding of the degree to which modern variation and evolutionary change in orbital and overall craniofacial morphology may help explain the common eye form association with this condition. Recent research into long and short-term evolution of the human orbit reveals a number of changes in this feature, and particularly since the Upper Paleolithic. These include a reduction in orbital depth, a decrease in anterior projection of the upper and lower orbital margins, and most notably, a reduction in orbital volume since the Holocene in East Asia. Reduced orbital volume in this geographic region could exacerbate an existing trend in recent hominin evolution toward larger eyes in smaller orbits, and may help explain the unusually high frequency of myopia in East Asian populations. The objective of the current study is to test a null hypothesis of no relationship between a ratio of orbit to eye volume and spherical equivalent refractive error (SER) in a sample of Chinese adults, and examine how relative size of the eye within the orbit relates to SER between the sexes and across the sample population. Analysis of the orbit, eye, and SER reveals a strong relationship between relative size of the eye within the orbit and the severity of myopic refractive error. An orbit/eye ratio of 3 for females and 3.5 for males (or an eye that occupies approximately 34% and 29% of the orbit, respectively), designates a clear threshold at which myopia develops, and becomes progressively worse as the eye continues to occupy a greater proportion of the orbital cavity. These results indicate that relative size of the eye within the orbit is an important factor in the development of myopia, and suggests that individuals with large eyes in small orbits lack space for adequate development of ocular tissues, leading to compression and distortion of the lithesome globe

  14. An Evolutionary Robotics Approach to the Control of Plant Growth and Motion: Modeling Plants and Crossing the Reality Gap

    DEFF Research Database (Denmark)

    Wahby, Mostafa; Hofstadler, Daniel Nicolas; Heinrich, Mary Katherine

    2016-01-01

    approach where task performance is determined by monitoring the plant's reaction. First, we do initial plant experiments with simple, predetermined controllers. Then we use image sampling data as a model of the dynamics of the plant tip xy position. Second, we use this approach to evolve robot controllers...... in simulation. The task is to make the plant approach three predetermined, distinct points in an xy-plane. Finally, we test the evolved controllers in real plant experiments and find that we cross the reality gap successfully. We shortly describe how we have extended from plant tip to many points on the plant...

  15. Evolutionary Statistical Procedures

    CERN Document Server

    Baragona, Roberto; Poli, Irene

    2011-01-01

    This proposed text appears to be a good introduction to evolutionary computation for use in applied statistics research. The authors draw from a vast base of knowledge about the current literature in both the design of evolutionary algorithms and statistical techniques. Modern statistical research is on the threshold of solving increasingly complex problems in high dimensions, and the generalization of its methodology to parameters whose estimators do not follow mathematically simple distributions is underway. Many of these challenges involve optimizing functions for which analytic solutions a

  16. Sex differences in motor and cognitive abilities predicted from human evolutionary history with some implications for models of the visual system.

    Science.gov (United States)

    Sanders, Geoff

    2013-01-01

    This article expands the knowledge base available to sex researchers by reviewing recent evidence for sex differences in coincidence-anticipation timing (CAT), motor control with the hand and arm, and visual processing of stimuli in near and far space. In CAT, the differences are between sex and, therefore, typical of other widely reported sex differences. Men perform CAT tasks with greater accuracy and precision than women, who tend to underestimate time to arrival. Null findings arise because significant sex differences are found with easy but not with difficult tasks. The differences in motor control and visual processing are within sex, and they underlie reciprocal patterns of performance in women and men. Motor control is exerted better by women with the hand than the arm. In contrast, men showed the reverse pattern. Visual processing is performed better by women with stimuli within hand reach (near space) as opposed to beyond hand reach (far space); men showed the reverse pattern. The sex differences seen in each of these three abilities are consistent with the evolutionary selection of men for hunting-related skills and women for gathering-related skills. The implications of the sex differences in visual processing for two visual system models of human vision are discussed.

  17. Avian malaria: a new lease of life for an old experimental model to study the evolutionary ecology of Plasmodium.

    Science.gov (United States)

    Pigeault, Romain; Vézilier, Julien; Cornet, Stéphane; Zélé, Flore; Nicot, Antoine; Perret, Philippe; Gandon, Sylvain; Rivero, Ana

    2015-08-19

    Avian malaria has historically played an important role as a model in the study of human malaria, being a stimulus for the development of medical parasitology. Avian malaria has recently come back to the research scene as a unique animal model to understand the ecology and evolution of the disease, both in the field and in the laboratory. Avian malaria is highly prevalent in birds and mosquitoes around the world and is amenable to laboratory experimentation at each stage of the parasite's life cycle. Here, we take stock of 5 years of experimental laboratory research carried out using Plasmodium relictum SGS1, the most prevalent avian malaria lineage in Europe, and its natural vector, the mosquito Culex pipiens. For this purpose, we compile and analyse data obtained in our laboratory in 14 different experiments. We provide statistical relationships between different infection-related parameters, including parasitaemia, gametocytaemia, host morbidity (anaemia) and transmission rates to mosquitoes. This analysis provides a wide-ranging picture of the within-host and between-host parameters that may bear on malaria transmission and epidemiology. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  18. Unusual sugar specificity of banana lectin from Musa paradisiaca and its probable evolutionary origin. Crystallographic and modelling studies.

    Science.gov (United States)

    Singh, D D; Saikrishnan, K; Kumar, Prashant; Surolia, A; Sekar, K; Vijayan, M

    2005-10-01

    The crystal structure of a complex of methyl-alpha-D-mannoside with banana lectin from Musa paradisiaca reveals two primary binding sites in the lectin, unlike in other lectins with beta-prism I fold which essentially consists of three Greek key motifs. It has been suggested that the fold evolved through successive gene duplication and fusion of an ancestral Greek key motif. In other lectins, all from dicots, the primary binding site exists on one of the three motifs in the three-fold symmetric molecule. Banana is a monocot, and the three motifs have not diverged enough to obliterate sequence similarity among them. Two Greek key motifs in it carry one primary binding site each. A common secondary binding site exists on the third Greek key. Modelling shows that both the primary sites can support 1-2, 1-3, and 1-6 linked mannosides with the second residue interacting in each case primarily with the secondary binding site. Modelling also readily leads to a bound branched mannopentose with the nonreducing ends of the two branches anchored at the two primary binding sites, providing a structural explanation for the lectin's specificity for branched alpha-mannans. A comparison of the dimeric banana lectin with other beta-prism I fold lectins, provides interesting insights into the variability in their quaternary structure.

  19. Evolutionary computation in zoology and ecology.

    Science.gov (United States)

    Boone, Randall B

    2017-12-01

    Evolutionary computational methods have adopted attributes of natural selection and evolution to solve problems in computer science, engineering, and other fields. The method is growing in use in zoology and ecology. Evolutionary principles may be merged with an agent-based modeling perspective to have individual animals or other agents compete. Four main categories are discussed: genetic algorithms, evolutionary programming, genetic programming, and evolutionary strategies. In evolutionary computation, a population is represented in a way that allows for an objective function to be assessed that is relevant to the problem of interest. The poorest performing members are removed from the population, and remaining members reproduce and may be mutated. The fitness of the members is again assessed, and the cycle continues until a stopping condition is met. Case studies include optimizing: egg shape given different clutch sizes, mate selection, migration of wildebeest, birds, and elk, vulture foraging behavior, algal bloom prediction, and species richness given energy constraints. Other case studies simulate the evolution of species and a means to project shifts in species ranges in response to a changing climate that includes competition and phenotypic plasticity. This introduction concludes by citing other uses of evolutionary computation and a review of the flexibility of the methods. For example, representing species' niche spaces subject to selective pressure allows studies on cladistics, the taxon cycle, neutral versus niche paradigms, fundamental versus realized niches, community structure and order of colonization, invasiveness, and responses to a changing climate.

  20. ON THE RELIABILITY OF STELLAR AGES AND AGE SPREADS INFERRED FROM PRE-MAIN-SEQUENCE EVOLUTIONARY MODELS

    International Nuclear Information System (INIS)

    Hosokawa, Takashi; Offner, Stella S. R.; Krumholz, Mark R.

    2011-01-01

    We revisit the problem of low-mass pre-main-sequence stellar evolution and its observational consequences for where stars fall on the Hertzsprung-Russell diagram (HRD). In contrast to most previous work, our models follow stars as they grow from small masses via accretion, and we perform a systematic study of how the stars' HRD evolution is influenced by their initial radius, by the radiative properties of the accretion flow, and by the accretion history, using both simple idealized accretion histories and histories taken from numerical simulations of star cluster formation. We compare our numerical results to both non-accreting isochrones and to the positions of observed stars in the HRD, with a goal of determining whether both the absolute ages and the age dispersions inferred from non-accreting isochrones are reliable. We show that non-accreting isochrones can sometimes overestimate stellar ages for more massive stars (those with effective temperatures above ∼3500 K), thereby explaining why non-accreting isochrones often suggest a systematic age difference between more and less massive stars in the same cluster. However, we also find the only way to produce a similar overestimate for the ages of cooler stars is if these stars grow from ∼0.01 M sun seed protostars that are an order of magnitude smaller than predicted by current theoretical models, and if the size of the seed protostar correlates systematically with the final stellar mass at the end of accretion. We therefore conclude that, unless both of these conditions are met, inferred ages and age spreads for cool stars are reliable, at least to the extent that the observed bolometric luminosities and temperatures are accurate. Finally, we note that the time dependence of the mass accretion rate has remarkably little effect on low-mass stars' evolution on the HRD, and that such time dependence may be neglected for all stars except those with effective temperatures above ∼4000 K.

  1. Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

    Directory of Open Access Journals (Sweden)

    Humaira Adnan

    Full Text Available Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD, to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon, to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin containing genetically inactivated (± an N-terminal polyleucine tail A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF mutant (5-10x, F508delCFTR Golgi maturation (<10x, cell surface expression (20x and chloride transport (2x in F508del CFTR transfected cells and patient-derived F508delCFTR bronchiolar epithelia, without apparent cytopathology. These toxoids also increase glucocerobrosidase (GCC in N370SGCC Gaucher Disease fibroblasts (3x, another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

  2. Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

    Science.gov (United States)

    Adnan, Humaira; Zhang, Zhenbo; Park, Hyun-Joo; Tailor, Chetankumar; Che, Clare; Kamani, Mustafa; Spitalny, George; Binnington, Beth; Lingwood, Clifford

    2016-01-01

    Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin) containing genetically inactivated (± an N-terminal polyleucine tail) A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF) mutant (5-10x), F508delCFTR Golgi maturation (glucocerobrosidase (GCC) in N370SGCC Gaucher Disease fibroblasts (3x), another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

  3. Paleoclimatic modeling and phylogeography of least killifish, Heterandria formosa: insights into Pleistocene expansion-contraction dynamics and evolutionary history of North American Coastal Plain freshwater biota.

    Science.gov (United States)

    Bagley, Justin C; Sandel, Michael; Travis, Joseph; Lozano-Vilano, María de Lourdes; Johnson, Jerald B

    2013-10-09

    expansion-contraction model, even as the genetic data suggest additional ecological influences on population structure. While evidence for Plio-Pleistocene Gulf Coast vicariance is well described for many freshwater species presently codistributed with H. formosa, this species demography and diversification departs notably from this pattern. Species-specific expansion-contraction dynamics may therefore have figured more prominently in shaping Coastal Plain evolutionary history than previously thought. Our findings bolster growing appreciation for the complexity of phylogeographical structuring within North America's southern refugia, including responses of Coastal Plain freshwater biota to Pleistocene climatic fluctuations.

  4. An evolutionary model for collapsing molecular clouds and their star formation activity. II. Mass dependence of the star formation rate

    Energy Technology Data Exchange (ETDEWEB)

    Zamora-Avilés, Manuel; Vázquez-Semadeni, Enrique [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México, Apdo. Postal 3-72, Morelia, Michoacán 58089 (Mexico)

    2014-10-01

    We discuss the evolution and dependence on cloud mass of the star formation rate (SFR) and efficiency (SFE) of star-forming molecular clouds (MCs) within the scenario that clouds are undergoing global collapse and that the SFR is controlled by ionization feedback. We find that low-mass clouds (M {sub max} ≲ 10{sup 4} M {sub ☉}) spend most of their evolution at low SFRs, but end their lives with a mini-burst, reaching a peak SFR ∼10{sup 4} M {sub ☉} Myr{sup –1}, although their time-averaged SFR is only (SFR) ∼ 10{sup 2} M {sub ☉} Myr{sup –1}. The corresponding efficiencies are SFE{sub final} ≲ 60% and (SFE) ≲ 1%. For more massive clouds (M {sub max} ≳ 10{sup 5} M {sub ☉}), the SFR first increases and then reaches a plateau because the clouds are influenced by stellar feedback since earlier in their evolution. As a function of cloud mass, (SFR) and (SFE) are well represented by the fits (SFR) ≈ 100(1 + M {sub max}/1.4 × 10{sup 5} M {sub ☉}){sup 1.68} M {sub ☉} Myr{sup –1} and (SFE) ≈ 0.03(M {sub max}/2.5 × 10{sup 5} M {sub ☉}){sup 0.33}, respectively. Moreover, the SFR of our model clouds follows closely the SFR-dense gas mass relation recently found by Lada et al. during the epoch when their instantaneous SFEs are comparable to those of the clouds considered by those authors. Collectively, a Monte Carlo integration of the model-predicted SFR(M) over a Galactic giant molecular cloud mass spectrum yields values for the total Galactic SFR that are within half an order of magnitude of the relation obtained by Gao and Solomon. Our results support the scenario that star-forming MCs may be in global gravitational collapse and that the low observed values of the SFR and SFE are a result of the interruption of each SF episode, caused primarily by the ionizing feedback from massive stars.

  5. Evolutionary trends in Heteroptera

    NARCIS (Netherlands)

    Cobben, R.H.

    1968-01-01

    1. This work, the first volume of a series dealing with evolutionary trends in Heteroptera, is concerned with the egg system of about 400 species. The data are presented systematically in chapters 1 and 2 with a critical review of the literature after each family.

    2. Chapter 3 evaluates facts

  6. Applications of Evolutionary Computation

    NARCIS (Netherlands)

    Mora, Antonio M.; Squillero, Giovanni; Di Chio, C; Agapitos, Alexandros; Cagnoni, Stefano; Cotta, Carlos; Fernández De Vega, F; Di Caro, G A; Drechsler, R.; Ekárt, A; Esparcia-Alcázar, Anna I.; Farooq, M; Langdon, W B; Merelo-Guervós, J.J.; Preuss, M; Richter, O.-M.H.; Silva, Sara; Sim$\\$~oes, A; Squillero, Giovanni; Tarantino, Ernesto; Tettamanzi, Andrea G B; Togelius, J; Urquhart, Neil; Uyar, A S; Yannakakis, G N; Smith, Stephen L; Caserta, Marco; Ramirez, Adriana; Voß, Stefan; Squillero, Giovanni; Burelli, Paolo; Mora, Antonio M.; Squillero, Giovanni; Jan, Mathieu; Matthias, M; Di Chio, C; Agapitos, Alexandros; Cagnoni, Stefano; Cotta, Carlos; Fernández De Vega, F; Di Caro, G A; Drechsler, R.; Ekárt, A; Esparcia-Alcázar, Anna I.; Farooq, M; Langdon, W B; Merelo-Guervós, J.J.; Preuss, M; Richter, O.-M.H.; Silva, Sara; Sim$\\$~oes, A; Squillero, Giovanni; Tarantino, Ernesto; Tettamanzi, Andrea G B; Togelius, J; Urquhart, Neil; Uyar, A S; Yannakakis, G N; Caserta, Marco; Ramirez, Adriana; Voß, Stefan; Squillero, Giovanni; Burelli, Paolo; Esparcia-Alcazar, Anna I; Silva, Sara; Agapitos, Alexandros; Cotta, Carlos; De Falco, Ivanoe; Cioppa, Antonio Della; Diwold, Konrad; Ekart, Aniko; Tarantino, Ernesto; Vega, Francisco Fernandez De; Burelli, Paolo; Sim, Kevin; Cagnoni, Stefano; Simoes, Anabela; Merelo, J.J.; Urquhart, Neil; Haasdijk, Evert; Zhang, Mengjie; Squillero, Giovanni; Eiben, A E; Tettamanzi, Andrea G B; Glette, Kyrre; Rohlfshagen, Philipp; Schaefer, Robert; Caserta, Marco; Ramirez, Adriana; Voß, Stefan

    2015-01-01

    The application of genetic and evolutionary computation to problems in medicine has increased rapidly over the past five years, but there are specific issues and challenges that distinguish it from other real-world applications. Obtaining reliable and coherent patient data, establishing the clinical

  7. Evolutionary perspectives on ageing.

    Science.gov (United States)

    Reichard, Martin

    2017-10-01

    From an evolutionary perspective, ageing is a decrease in fitness with chronological age - expressed by an increase in mortality risk and/or decline in reproductive success and mediated by deterioration of functional performance. While this makes ageing intuitively paradoxical - detrimental to individual fitness - evolutionary theory offers answers as to why ageing has evolved. In this review, I first briefly examine the classic evolutionary theories of ageing and their empirical tests, and highlight recent findings that have advanced our understanding of the evolution of ageing (condition-dependent survival, positive pleiotropy). I then provide an overview of recent theoretical extensions and modifications that accommodate those new discoveries. I discuss the role of indeterminate (asymptotic) growth for lifetime increases in fecundity and ageing trajectories. I outline alternative views that challenge a universal existence of senescence - namely the lack of a germ-soma distinction and the ability of tissue replacement and retrogression to younger developmental stages in modular organisms. I argue that rejuvenation at the organismal level is plausible, but includes a return to a simple developmental stage. This may exempt a particular genotype from somatic defects but, correspondingly, removes any information acquired during development. A resolution of the question of whether a rejuvenated individual is the same entity is central to the recognition of whether current evolutionary theories of ageing, with their extensions and modifications, can explain the patterns of ageing across the Tree of Life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Editorial overview: Evolutionary psychology

    NARCIS (Netherlands)

    Gangestad, S.W.; Tybur, J.M.

    2016-01-01

    Functional approaches in psychology - which ask what behavior is good for - are almost as old as scientific psychology itself. Yet sophisticated, generative functional theories were not possible until developments in evolutionary biology in the mid-20th century. Arising in the last three decades,

  9. Biochemistry and evolutionary biology

    Indian Academy of Sciences (India)

    Biochemical information has been crucial for the development of evolutionary biology. On the one hand, the sequence information now appearing is producing a huge increase in the amount of data available for phylogenetic analysis; on the other hand, and perhaps more fundamentally, it allows understanding of the ...

  10. Evolutionary Biology Today

    Indian Academy of Sciences (India)

    Hindi and English. Port 1. Resonance, Vo1.7 ... they use. Of course, many evolutionary biologists do work with fossils or DNA, or both, but there are also large numbers of ... The first major division that I like to make is between studies focussed ...

  11. Learning: An Evolutionary Analysis

    Science.gov (United States)

    Swann, Joanna

    2009-01-01

    This paper draws on the philosophy of Karl Popper to present a descriptive evolutionary epistemology that offers philosophical solutions to the following related problems: "What happens when learning takes place?" and "What happens in human learning?" It provides a detailed analysis of how learning takes place without any direct transfer of…

  12. Complex systems, evolutionary planning?

    NARCIS (Netherlands)

    Bertolini, L.; de Roo, G.; Silva, E.A.

    2010-01-01

    Coping with uncertainty is a defining challenge for spatial planners. Accordingly, most spatial planning theories and methods are aimed at reducing uncertainty. However, the question is what should be done when this seems impossible? This chapter proposes an evolutionary interpretation of spatial

  13. Molluscan Evolutionary Development

    DEFF Research Database (Denmark)

    Wanninger, Andreas Wilhelm Georg; Koop, Damien; Moshel-Lynch, Sharon

    2008-01-01

    Brought together by Winston F. Ponder and David R. Lindberg, thirty-six experts on the evolution of the Mollusca provide an up-to-date review of its evolutionary history. The Mollusca are the second largest animal phylum and boast a fossil record of over 540 million years. They exhibit remarkable...

  14. Evolutionary dynamics with fluctuating population sizes and strong mutualism

    Science.gov (United States)

    Chotibut, Thiparat; Nelson, David R.

    2015-08-01

    Game theory ideas provide a useful framework for studying evolutionary dynamics in a well-mixed environment. This approach, however, typically enforces a strictly fixed overall population size, deemphasizing natural growth processes. We study a competitive Lotka-Volterra model, with number fluctuations, that accounts for natural population growth and encompasses interaction scenarios typical of evolutionary games. We show that, in an appropriate limit, the model describes standard evolutionary games with both genetic drift and overall population size fluctuations. However, there are also regimes where a varying population size can strongly influence the evolutionary dynamics. We focus on the strong mutualism scenario and demonstrate that standard evolutionary game theory fails to describe our simulation results. We then analytically and numerically determine fixation probabilities as well as mean fixation times using matched asymptotic expansions, taking into account the population size degree of freedom. These results elucidate the interplay between population dynamics and evolutionary dynamics in well-mixed systems.

  15. Evolutionary dynamics with fluctuating population sizes and strong mutualism.

    Science.gov (United States)

    Chotibut, Thiparat; Nelson, David R

    2015-08-01

    Game theory ideas provide a useful framework for studying evolutionary dynamics in a well-mixed environment. This approach, however, typically enforces a strictly fixed overall population size, deemphasizing natural growth processes. We study a competitive Lotka-Volterra model, with number fluctuations, that accounts for natural population growth and encompasses interaction scenarios typical of evolutionary games. We show that, in an appropriate limit, the model describes standard evolutionary games with both genetic drift and overall population size fluctuations. However, there are also regimes where a varying population size can strongly influence the evolutionary dynamics. We focus on the strong mutualism scenario and demonstrate that standard evolutionary game theory fails to describe our simulation results. We then analytically and numerically determine fixation probabilities as well as mean fixation times using matched asymptotic expansions, taking into account the population size degree of freedom. These results elucidate the interplay between population dynamics and evolutionary dynamics in well-mixed systems.

  16. Bridging the gap between Schumpeterian competition and evolutionary game theory

    DEFF Research Database (Denmark)

    Andersen, Esben Sloth

    This paper suggests that the analysis of Schumpeterian competition within the Nelson-Winter model should be complemented with evolutionary game theory. This model and its limitations for density-dependent Schumpeterian strategies are presented in terms of the equations of evolutionary dynamics. F...

  17. RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus

    Science.gov (United States)

    Lenz, Tobias L; Eizaguirre, Christophe; Becker, Sven; Reusch, Thorsten BH

    2009-01-01

    Background In all jawed vertebrates, highly polymorphic genes of the major histocompatibility complex (MHC) encode antigen presenting molecules that play a key role in the adaptive immune response. Their polymorphism is composed of multiple copies of recently duplicated genes, each possessing many alleles within populations, as well as high nucleotide divergence between alleles of the same species. Experimental evidence is accumulating that MHC polymorphism is a result of balancing selection by parasites and pathogens. In order to describe MHC diversity and analyse the underlying mechanisms that maintain it, a reliable genotyping technique is required that is suitable for such highly variable genes. Results We present a genotyping protocol that uses Reference Strand-mediated Conformation Analysis (RSCA), optimised for recently duplicated MHC class IIB genes that are typical for many fish and bird species, including the three-spined stickleback, Gasterosteus aculeatus. In addition we use a comprehensive plasmid library of MHC class IIB alleles to determine the nucleotide sequence of alleles represented by RSCA allele peaks. Verification of the RSCA typing by cloning and sequencing demonstrates high congruency between both methods and provides new insight into the polymorphism of classical stickleback MHC genes. Analysis of the plasmid library additionally reveals the high resolution and reproducibility of the RSCA technique. Conclusion This new RSCA genotyping protocol offers a fast, but sensitive and reliable way to determine the MHC allele repertoire of three-spined sticklebacks. It therefore provides a valuable tool to employ this highly polymorphic and adaptive marker in future high-throughput studies of host-parasite co-evolution and ecological speciation in this emerging model organism. PMID:19291291

  18. RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus

    Directory of Open Access Journals (Sweden)

    Becker Sven

    2009-03-01

    Full Text Available Abstract Background In all jawed vertebrates, highly polymorphic genes of the major histocompatibility complex (MHC encode antigen presenting molecules that play a key role in the adaptive immune response. Their polymorphism is composed of multiple copies of recently duplicated genes, each possessing many alleles within populations, as well as high nucleotide divergence between alleles of the same species. Experimental evidence is accumulating that MHC polymorphism is a result of balancing selection by parasites and pathogens. In order to describe MHC diversity and analyse the underlying mechanisms that maintain it, a reliable genotyping technique is required that is suitable for such highly variable genes. Results We present a genotyping protocol that uses Reference Strand-mediated Conformation Analysis (RSCA, optimised for recently duplicated MHC class IIB genes that are typical for many fish and bird species, including the three-spined stickleback, Gasterosteus aculeatus. In addition we use a comprehensive plasmid library of MHC class IIB alleles to determine the nucleotide sequence of alleles represented by RSCA allele peaks. Verification of the RSCA typing by cloning and sequencing demonstrates high congruency between both methods and provides new insight into the polymorphism of classical stickleback MHC genes. Analysis of the plasmid library additionally reveals the high resolution and reproducibility of the RSCA technique. Conclusion This new RSCA genotyping protocol offers a fast, but sensitive and reliable way to determine the MHC allele repertoire of three-spined sticklebacks. It therefore provides a valuable tool to employ this highly polymorphic and adaptive marker in future high-throughput studies of host-parasite co-evolution and ecological speciation in this emerging model organism.

  19. Exploring Tradeoffs in Demand-Side and Supply-Side Management of Urban Water Resources Using Agent-Based Modeling and Evolutionary Computation

    Directory of Open Access Journals (Sweden)

    Lufthansa Kanta

    2015-11-01

    Full Text Available Urban water supply systems may be managed through supply-side and demand-side strategies, which focus on water source expansion and demand reductions, respectively. Supply-side strategies bear infrastructure and energy costs, while demand-side strategies bear costs of implementation and inconvenience to consumers. To evaluate the performance of demand-side strategies, the participation and water use adaptations of consumers should be simulated. In this study, a Complex Adaptive Systems (CAS framework is developed to simulate consumer agents that change their consumption to affect the withdrawal from the water supply system, which, in turn influences operational policies and long-term resource planning. Agent-based models are encoded to represent consumers and a policy maker agent and are coupled with water resources system simulation models. The CAS framework is coupled with an evolutionary computation-based multi-objective methodology to explore tradeoffs in cost, inconvenience to consumers, and environmental impacts for both supply-side and demand-side strategies. Decisions are identified to specify storage levels in a reservoir that trigger: (1 increases in the volume of water pumped through inter-basin transfers from an external reservoir; and (2 drought stages, which restrict the volume of water that is allowed for residential outdoor uses. The proposed methodology is demonstrated for Arlington, Texas, water supply system to identify non-dominated strategies for an historic drought decade. Results demonstrate that pumping costs associated with maximizing environmental reliability exceed pumping costs associated with minimizing restrictions on consumer water use.

  20. Molecular modeling of directed self-assembly of block copolymers: Fundamental studies of processing conditions and evolutionary pattern design

    Science.gov (United States)

    Khaira, Gurdaman Singh

    Rapid progress in the semi-conductor industry has pushed for smaller feature sizes on integrated electronic circuits. Current photo-lithographic techniques for nanofabrication have reached their technical limit and are problematic when printing features small enough to meet future industrial requirements. "Bottom-up'' techniques, such as the directed self-assembly (DSA) of block copolymers (BCP), are the primary contenders to compliment current "top-down'' photo-lithography ones. For industrial requirements, the defect density from DSA needs to be less than 1 defect per 10 cm by 10 cm. Knowledge of both material synthesis and the thermodynamics of the self-assembly process are required before optimal operating conditions can be found to produce results adequate for industry. The work present in this thesis is divided into three chapters, each discussing various aspects of DSA as studied via a molecular model that contains the essential physics of BCP self-assembly. Though there are various types of guiding fields that can be used to direct BCPs over large wafer areas with minimum defects, this study focuses only on chemically patterned substrates. The first chapter addresses optimal pattern design by describing a framework where molecular simulations of various complexities are coupled with an advanced optimization technique to find a pattern that directs a target morphology. It demonstrates the first ever study where BCP self-assembly on a patterned substrate is optimized using a three-dimensional description of the block-copolymers. For problems pertaining to DSA, the methodology is shown to converge much faster than the traditional random search approach. The second chapter discusses the metrology of BCP thin films using TEM tomography and X-ray scattering techniques, such as CDSAXS and GISAXS. X-ray scattering has the advantage of being able to quickly probe the average structure of BCP morphologies over large wafer areas; however, deducing the BCP morphology

  1. Sequencing Analysis of Mutant Allele $cdc$28-$srm$ of Protein Kinase CDC28 and Molecular Dynamics Study of Glycine-Rich Loop in Wild-Type and Mutant Allele G16S of CDK2 as Model

    CERN Document Server

    Koltovaya, N A; Kholmurodov, Kh T; Kretov, D A

    2005-01-01

    The central role that cyclin-dependent kinases play in the timing of cell division and the high incidence of genetic alteration of CDKs or deregulation of CDK inhibitors in a number of cancers make CDC28 of the yeast \\textit{Saccharomyces cerevisiae }very attractive model for studies of mechanisms of CDK regulation. Earlier it was found that certain gene mutations including \\textit{cdc28-srm} affect cell cycle progression, maintenance of different genetic structures and increase cell sensitivity to ionizing radiation. A~\\textit{cdc28-srm} mutation is not temperature-sensitive mutation and differs from the known \\textit{cdc28-ts }mutations because it has the evident phenotypic manifestations at 30 $^{\\circ}$C. Sequencing analysis of \\textit{cdc28-srm} revealed a single nucleotide substitution G20S. This is a third glycine in a conserved sequence GxGxxG in the G-rich loop positioned opposite the activation T-loop. Despite its demonstrated importance, the role of the G-loop has remained unclear. The crystal stru...

  2. Incorporation of an evolutionary algorithm to estimate transfer-functions for a parameter regionalization scheme of a rainfall-runoff model

    Science.gov (United States)

    Klotz, Daniel; Herrnegger, Mathew; Schulz, Karsten

    2016-04-01

    This contribution presents a framework, which enables the use of an Evolutionary Algorithm (EA) for the calibration and regionalization of the hydrological model COSEROreg. COSEROreg uses an updated version of the HBV-type model COSERO (Kling et al. 2014) for the modelling of hydrological processes and is embedded in a parameter regionalization scheme based on Samaniego et al. (2010). The latter uses subscale-information to estimate model via a-priori chosen transfer functions (often derived from pedotransfer functions). However, the transferability of the regionalization scheme to different model-concepts and the integration of new forms of subscale information is not straightforward. (i) The usefulness of (new) single sub-scale information layers is unknown beforehand. (ii) Additionally, the establishment of functional relationships between these (possibly meaningless) sub-scale information layers and the distributed model parameters remain a central challenge in the implementation of a regionalization procedure. The proposed method theoretically provides a framework to overcome this challenge. The implementation of the EA encompasses the following procedure: First, a formal grammar is specified (Ryan et al., 1998). The construction of the grammar thereby defines the set of possible transfer functions and also allows to incorporate hydrological domain knowledge into the search itself. The EA iterates over the given space by combining parameterized basic functions (e.g. linear- or exponential functions) and sub-scale information layers into transfer functions, which are then used in COSEROreg. However, a pre-selection model is applied beforehand to sort out unfeasible proposals by the EA and to reduce the necessary model runs. A second optimization routine is used to optimize the parameters of the transfer functions proposed by the EA. This concept, namely using two nested optimization loops, is inspired by the idea of Lamarckian Evolution and Baldwin Effect

  3. Evaluation of tall rice mutant

    International Nuclear Information System (INIS)

    Hakim, L.; Azam, M.A.; Miah, A.J.; Mansur, M.A.; Akanda, H.R.

    1989-01-01

    One tall mutant (Mut NS1) of rice variety Nizersail was put to multilocation on-farm trial. It showed improvement over the parent in respect of by earlier maturity and higher grain yield at all locations and thus it appears as an improved mutant of Nizersail. (author). 6 refs

  4. ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    McGown, Alexander; Shaw, Dame Pamela J; Ramesh, Tennore

    2016-07-26

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2-3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. Riluzole, the only neuroprotective drug for ALS provides life extension of only 3 months on average. Thishighlights the need for compound screening in disease models to identify new neuroprotective therapies for this disease. Zebrafish is an emerging model system that is well suited for the study of diseasepathophysiology and also for high throughput (HT) drug screening. The mutant sod1 zebrafish model of ALS mimics the hallmark features of ALS. Using a fluorescence based readout of neuronal stress, we developed a high throughput (HT) screen to identify neuroprotective compounds. Here we show that the zebrafish screen is a robust system that can be used to rapidly screen thousands ofcompounds and also demonstrate that riluzole is capable of reducing neuronal stress in this model system. The screen shows optimal quality control, maintaining a high sensitivity and specificity withoutcompromising throughput. Most importantly, we demonstrate that many compounds previously failed in human clinical trials, showed no stress reducing activity in the zebrafish assay. We conclude that HT drug screening using a mutant sod1 zebrafish is a reliable model system which supplemented with secondary assays would be useful in identifying drugs with potential for neuroprotective efficacy in ALS.

  5. Within-host selection of drug resistance in a mouse model reveals dose-dependent selection of atovaquone resistance mutations

    NARCIS (Netherlands)

    Nuralitha, Suci; Murdiyarso, Lydia S.; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I.M.; Marzuki, Sangkot

    2017-01-01

    The evolutionary selection of malaria parasites within an individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutants in mouse models reflecting two different causes of failure of malaria treatment, an inadequate

  6. Evolutionary stability concepts in a stochastic environment

    Science.gov (United States)

    Zheng, Xiu-Deng; Li, Cong; Lessard, Sabin; Tao, Yi

    2017-09-01

    Over the past 30 years, evolutionary game theory and the concept of an evolutionarily stable strategy have been not only extensively developed and successfully applied to explain the evolution of animal behaviors, but also widely used in economics and social sciences. Nonetheless, the stochastic dynamical properties of evolutionary games in randomly fluctuating environments are still unclear. In this study, we investigate conditions for stochastic local stability of fixation states and constant interior equilibria in a two-phenotype model with random payoffs following pairwise interactions. Based on this model, we develop the concepts of stochastic evolutionary stability (SES) and stochastic convergence stability (SCS). We show that the condition for a pure strategy to be SES and SCS is more stringent than in a constant environment, while the condition for a constant mixed strategy to be SES is less stringent than the condition to be SCS, which is less stringent than the condition in a constant environment.

  7. Outrun or Outmaneuver: Predator-Prey Interactions as a Model System for Integrating Biomechanical Studies in a Broader Ecological and Evolutionary Context.

    Science.gov (United States)

    Moore, Talia Y; Biewener, Andrew A

    2015-12-01

    Behavioral studies performed in natural habitats provide a context for the development of hypotheses and the design of experiments relevant both to biomechanics and to evolution. In particular, predator-prey interactions are a model system for integrative study because success or failure of predation has a direct effect on fitness and drives the evolution of specialized performance in both predator and prey. Although all predators share the goal of capturing prey, and all prey share the goal of survival, the behavior of predators and prey are diverse in nature. This article presents studies of some predator-prey interactions sharing common predation strategies that reveal general principles governing the behaviors of predator and prey, even in distantly related taxa. Studies of predator-prey interactions also reveal that maximal performance observed in a laboratory setting is not necessarily the performance that determines fitness. Thus, considering locomotion in the context of predation ecology can aid in evolutionarily relevant experimental design. Classification by strategy reveals that displaying unpredictable trajectories is a relevant anti-predator behavior in response to multiple predation strategies. A predator's perception and pursuit of prey can be affected indirectly by divergent locomotion of similar animals that share an ecosystem. Variation in speed and direction of locomotion that directly increases the unpredictability of a prey's trajectory can be increased through genetic mutation that affects locomotor patterns, musculoskeletal changes that affect maneuverability, and physical interactions between an animal and the environment. By considering the interconnectedness of ecology, physical constraints, and the evolutionary history of behavior, studies in biomechanics can be designed to inform each of these fields. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights

  8. From where to what: a neuroanatomically based evolutionary model of the emergence of speech in humans [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Oren Poliva

    2016-01-01

    Full Text Available In the brain of primates, the auditory cortex connects with the frontal lobe via the temporal pole (auditory ventral stream; AVS and via the inferior parietal lobe (auditory dorsal stream; ADS. The AVS is responsible for sound recognition, and the ADS for sound-localization, voice detection and integration of calls with faces. I propose that the primary role of the ADS in non-human primates is the detection and response to contact calls. These calls are exchanged between tribe members (e.g., mother-offspring and are used for monitoring location. Detection of contact calls occurs by the ADS identifying a voice, localizing it, and verifying that the corresponding face is out of sight. Once a contact call is detected, the primate produces a contact call in return via descending connections from the frontal lobe to a network of limbic and brainstem regions. Because the ADS of present day humans also performs speech production, I further propose an evolutionary course for the transition from contact call exchange to an early form of speech. In accordance with this model, structural changes to the ADS endowed early members of the genus Homo with partial vocal control. This development was beneficial as it enabled offspring to modify their contact calls with intonations for signaling high or low levels of distress to their mother. Eventually, individuals were capable of participating in yes-no question-answer conversations. In these conversations the offspring emitted a low-level distress call for inquiring about the safety of objects (e.g., food, and his/her mother responded with a high- or low-level distress call to signal approval or disapproval of the interaction. Gradually, the ADS and its connections with brainstem motor regions became more robust and vocal control became more volitional. Speech emerged once vocal control was sufficient for inventing novel calls.

  9. From where to what: a neuroanatomically based evolutionary model of the emergence of speech in humans [version 3; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Oren Poliva

    2017-09-01

    Full Text Available In the brain of primates, the auditory cortex connects with the frontal lobe via the temporal pole (auditory ventral stream; AVS and via the inferior parietal lobe (auditory dorsal stream; ADS. The AVS is responsible for sound recognition, and the ADS for sound-localization, voice detection and integration of calls with faces. I propose that the primary role of the ADS in non-human primates is the detection and response to contact calls. These calls are exchanged between tribe members (e.g., mother-offspring and are used for monitoring location. Detection of contact calls occurs by the ADS identifying a voice, localizing it, and verifying that the corresponding face is out of sight. Once a contact call is detected, the primate produces a contact call in return via descending connections from the frontal lobe to a network of limbic and brainstem regions. Because the ADS of present day humans also performs speech production, I further propose an evolutionary course for the transition from contact call exchange to an early form of speech. In accordance with this model, structural changes to the ADS endowed early members of the genus Homo with partial vocal control. This development was beneficial as it enabled offspring to modify their contact calls with intonations for signaling high or low levels of distress to their mother. Eventually, individuals were capable of participating in yes-no question-answer conversations. In these conversations the offspring emitted a low-level distress call for inquiring about the safety of objects (e.g., food, and his/her mother responded with a high- or low-level distress call to signal approval or disapproval of the interaction. Gradually, the ADS and its connections with brainstem motor regions became more robust and vocal control became more volitional. Speech emerged once vocal control was sufficient for inventing novel calls.

  10. Markov Networks in Evolutionary Computation

    CERN Document Server

    Shakya, Siddhartha

    2012-01-01

    Markov networks and other probabilistic graphical modes have recently received an upsurge in attention from Evolutionary computation community, particularly in the area of Estimation of distribution algorithms (EDAs).  EDAs have arisen as one of the most successful experiences in the application of machine learning methods in optimization, mainly due to their efficiency to solve complex real-world optimization problems and their suitability for theoretical analysis. This book focuses on the different steps involved in the conception, implementation and application of EDAs that use Markov networks, and undirected models in general. It can serve as a general introduction to EDAs but covers also an important current void in the study of these algorithms by explaining the specificities and benefits of modeling optimization problems by means of undirected probabilistic models. All major developments to date in the progressive introduction of Markov networks based EDAs are reviewed in the book. Hot current researc...

  11. Evolutionary Models of Irregular Warfare

    Science.gov (United States)

    2013-03-01

    the poorest data—perhaps in part because of political nervousness about advertising estimates of enemy strengths after early optimism in Iraq, as...repro- duction. These adaptations include both physiological and behavioral strategies ranging from armour and immunity to complex nervous sys- tems

  12. Defining fitness in evolutionary models

    Indian Academy of Sciences (India)

    2008-12-23

    Dec 23, 2008 ... guish it from rates of increase calculated with other factors included). .... offspring produced by a female at the end of the season that survive to ...... VII. The demography and evolution of iteroparity. Am. Nat. 133, 901–923.

  13. Evolutionary constrained optimization

    CERN Document Server

    Deb, Kalyanmoy

    2015-01-01

    This book makes available a self-contained collection of modern research addressing the general constrained optimization problems using evolutionary algorithms. Broadly the topics covered include constraint handling for single and multi-objective optimizations; penalty function based methodology; multi-objective based methodology; new constraint handling mechanism; hybrid methodology; scaling issues in constrained optimization; design of scalable test problems; parameter adaptation in constrained optimization; handling of integer, discrete and mix variables in addition to continuous variables; application of constraint handling techniques to real-world problems; and constrained optimization in dynamic environment. There is also a separate chapter on hybrid optimization, which is gaining lots of popularity nowadays due to its capability of bridging the gap between evolutionary and classical optimization. The material in the book is useful to researchers, novice, and experts alike. The book will also be useful...

  14. Topical grape seed proanthocyandin extract reduces sunburn cells and mutant p53 positive epidermal cell formation, and prevents depletion of Langerhans cells in an acute sunburn model.

    Science.gov (United States)

    Yuan, Xiao-Ying; Liu, Wei; Hao, Jian-Chun; Gu, Wei-Jie; Zhao, Yan-Shuang

    2012-01-01

    The purpose of this study was to investigate whether grape seed proanthocyanidin extract (GSPE) can provide photoprotection against ultraviolet (UV) irradiation. Study has shown that GSPE is a natural oxidant, and is used in many fields such as ischemia-reperfusion injury, chronic pancreatitis, and even cancer. However, the effect of GSPE on UV irradiation is as yet unknown. Cutaneous areas on the backs of normal volunteers were untreated or treated with GSPE solutions or vehicles 30 min before exposure to two minimal erythema doses (MED) of solar simulated radiation. Cutaneous areas at different sites were examined histologically for the number of sunburn cells, or immunohistochemically for Langerhans cells and mutant p53 epidermal cells. On histological and immunohistochemical examination, skin treated with GSPE before UV radiation showed fewer sunburn cells and mutant p53-positive epidermal cells and more Langerhans cells compared with skin treated with 2-MED UV radiation only (p<0.001, p<0.001, and p<0.01, respectively). GSPE may be a possible preventive agent for photoprotection.

  15. Introduction to Evolutionary Algorithms

    CERN Document Server

    Yu, Xinjie

    2010-01-01

    Evolutionary algorithms (EAs) are becoming increasingly attractive for researchers from various disciplines, such as operations research, computer science, industrial engineering, electrical engineering, social science, economics, etc. This book presents an insightful, comprehensive, and up-to-date treatment of EAs, such as genetic algorithms, differential evolution, evolution strategy, constraint optimization, multimodal optimization, multiobjective optimization, combinatorial optimization, evolvable hardware, estimation of distribution algorithms, ant colony optimization, particle swarm opti

  16. Biochemical analyses and molecular modeling explain the functional loss of 17β-hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian patients with 46, XY Disorders of Sex Development.

    Science.gov (United States)

    Engeli, Roger T; Rhouma, Bochra Ben; Sager, Christoph P; Tsachaki, Maria; Birk, Julia; Fakhfakh, Faiza; Keskes, Leila; Belguith, Neila; Odermatt, Alex

    2016-01-01

    Mutations in the HSD17B3 gene resulting in 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency cause 46, XY Disorders of Sex Development (46, XY DSD). Approximately 40 different mutations in HSD17B3 have been reported; only few mutant enzymes have been mechanistically investigated. Here, we report novel compound heterozygous mutations in HSD17B3, composed of the nonsense mutation C206X and the missense mutation G133R, in three Tunisian patients from two non-consanguineous families. Mutants C206X and G133R were constructed by site-directed mutagenesis and expressed in HEK-293 cells. The truncated C206X enzyme, lacking part of the substrate binding pocket, was moderately expressed and completely lost its enzymatic activity. Wild-type 17β-HSD3 and mutant G133R showed comparable expression levels and intracellular localization. The conversion of Δ4-androstene-3,17-dione (androstenedione) to testosterone was almost completely abolished for mutant G133R compared with wild-type 17β-HSD3. To obtain further mechanistic insight, G133 was mutated to alanine, phenylalanine and glutamine. G133Q and G133F were almost completely inactive, whereas G133A displayed about 70% of wild-type activity. Sequence analysis revealed that G133 on 17β-HSD3 is located in a motif highly conserved in 17β-HSDs and other short-chain dehydrogenase/reductase (SDR) enzymes. A homology model of 17β-HSD3 predicted that arginine or any other bulky residue at position 133 causes steric hindrance of cofactor NADPH binding, whereas substrate binding seems to be unaffected. The results indicate an essential role of G133 in the arrangement of the cofactor binding pocket, thus explaining the loss-of-function of 17β-HSD3 mutant G133R in the patients investigated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The Swedish mutant barley collection

    International Nuclear Information System (INIS)

    1989-01-01

    Full text: The Swedish mutation research programme in barley began about 50 years ago and has mainly been carried out at Svaloev in co-operation with the institute of Genetics at the University of Lund. The collection has been produced from different Swedish high-yielding spring barley varieties, using the following mutagens: X-rays, neutrons, several organic chemical compounds such as ethyleneimine, several sulfonate derivatives and the inorganic chemical mutagen sodium azide. Nearly 10,000 barley mutants are stored in the Nordic Gene Bank and documented in databases developed by Udda Lundquist, Svaloev AB. The collection consists of the following nine categories with 94 different types of mutants: 1. Mutants with changes in the spike and spikelets; 2. Changes in culm length and culm composition; 3. Changes in growth types; 4. Physiological mutants; 5. Changes in awns; 6. Changes in seed size and shape; 7. Changes in leaf blades; 8. Changes in anthocyanin and colour; 9. Resistance to barley powdery mildew. Barley is one of the most thoroughly investigated crops in terms of induction of mutations and mutation genetics. So far, about half of the mutants stored at the Nordic Gene Bank, have been analysed genetically; They constitute, however, only a minority of the 94 different mutant types. The genetic analyses have given valuable insights into the mutation process but also into the genetic architecture of various characters. A number of mutants of two-row barley have been registered and commercially released. One of the earliest released, Mari, an early maturing, daylength neutral, straw stiff mutant, is still grown in Iceland. The Swedish mutation material has been used in Sweden, but also in other countries, such as Denmark, Germany, and USA, for various studies providing a better understanding of the barley genome. The collection will be immensely valuable for future molecular genetical analyses of clone mutant genes. (author)

  18. The Swedish mutant barley collection

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-07-01

    Full text: The Swedish mutation research programme in barley began about 50 years ago and has mainly been carried out at Svaloev in co-operation with the institute of Genetics at the University of Lund. The collection has been produced from different Swedish high-yielding spring barley varieties, using the following mutagens: X-rays, neutrons, several organic chemical compounds such as ethyleneimine, several sulfonate derivatives and the inorganic chemical mutagen sodium azide. Nearly 10,000 barley mutants are stored in the Nordic Gene Bank and documented in databases developed by Udda Lundquist, Svaloev AB. The collection consists of the following nine categories with 94 different types of mutants: 1. Mutants with changes in the spike and spikelets; 2. Changes in culm length and culm composition; 3. Changes in growth types; 4. Physiological mutants; 5. Changes in awns; 6. Changes in seed size and shape; 7. Changes in leaf blades; 8. Changes in anthocyanin and colour; 9. Resistance to barley powdery mildew. Barley is one of the most thoroughly investigated crops in terms of induction of mutations and mutation genetics. So far, about half of the mutants stored at the Nordic Gene Bank, have been analysed genetically; They constitute, however, only a minority of the 94 different mutant types. The genetic analyses have given valuable insights into the mutation process but also into the genetic architecture of various characters. A number of mutants of two-row barley have been registered and commercially released. One of the earliest released, Mari, an early maturing, daylength neutral, straw stiff mutant, is still grown in Iceland. The Swedish mutation material has been used in Sweden, but also in other countries, such as Denmark, Germany, and USA, for various studies providing a better understanding of the barley genome. The collection will be immensely valuable for future molecular genetical analyses of clone mutant genes. (author)

  19. The effects of modeled microgravity on growth kinetics, antibiotic susceptibility, cold growth, and the virulence potential of a Yersinia pestis ymoA-deficient mutant and its isogenic parental strain.

    Science.gov (United States)

    Lawal, Abidat; Kirtley, Michelle L; van Lier, Christina J; Erova, Tatiana E; Kozlova, Elena V; Sha, Jian; Chopra, Ashok K; Rosenzweig, Jason A

    2013-09-01

    Previously, we reported that there was no enhancement in the virulence potential (as measured by cell culture infections) of the bacterial pathogen Yersinia pestis (YP) following modeled microgravity/clinorotation growth. We have now further characterized the effects of clinorotation (CR) on YP growth kinetics, antibiotic sensitivity, cold growth, and YP's virulence potential in a murine model of infection. Surprisingly, none of the aforementioned phenotypes were altered. To better understand why CR did not enhance YP's virulence potential as it did for other bacterial pathogens, a YP ΔymoA isogenic mutant in the KIM/D27 background strain that is unable to produce the histone-like YmoA protein and influences DNA topography was used in both cell culture and murine models of infection. YmoA represses type three secretion system (T3SS) virulence gene expression in the yersiniae. Similar to our CR-grown parental YP strain data, the CR-grown ΔymoA mutant induced reduced HeLa cell cytotoxicity with concomitantly decreased Yersinia outer protein E (YopE) and low calcium response V (LcrV) antigen production and secretion. Important, however, were our findings that, although no significant differences were observed in survival of mice infected intraperitoneally with either normal gravity (NG)- or CR-grown parental YP, the ΔymoA mutant induced significantly more mortality in infected mice than did the parental strain following CR growth. Taken together, our data demonstrate that CR did enhance the virulence potential of the YP ΔymoA mutant in a murine infection model (relative to the CR-grown parental strain), despite inducing less HeLa cell rounding in our cell culture infection assay due to reduced T3SS activity. Therefore, CR, which induces a unique type of bacterial stress, might be enhancing YP's virulence potential in vivo through a T3SS-independent mechanism when the histone-like YmoA protein is absent.

  20. BEAST: Bayesian evolutionary analysis by sampling trees

    Directory of Open Access Journals (Sweden)

    Drummond Alexei J

    2007-11-01

    Full Text Available Abstract Background The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based models suitable for both within- and between-species sequence data are implemented. Results BEAST version 1.4.6 consists of 81000 lines of Java source code, 779 classes and 81 packages. It provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions. BEAST source code is object-oriented, modular in design and freely available at http://beast-mcmc.googlecode.com/ under the GNU LGPL license. Conclusion BEAST is a powerful and flexible evolutionary analysis package for molecular sequence variation. It also provides a resource for the further development of new models and statistical methods of evolutionary analysis.

  1. Induction and characterization of Arabidopsis mutants by Ion beam

    International Nuclear Information System (INIS)

    Yoon, Y. H.; Choi, J. D.; Park, J. Y.; Lee, J. R.; Sohn, H. S.

    2008-03-01

    This study was conducted to search the proper conditions and times for irradiating proton beam to seeds generally used for induction of mutant. Arabidopsis as model plants has good characters that is a short generation time, producing a lot of seeds, sequenced genome, developed maker. This points were the best materials for plant breeding for this study. The data of inducing mutants of Arabidopsis is used to be applicate to crops have more longer generation that is the final goals of this study. The goals of this project were to inducing and characterizing arabidopsis mutants by the proton ion beam and γ-ray. As well as, the purpose of this study was securing more than 10 lines of arabidopsis mutants in this project and also to know the changed DNA structure of the mutants using the basic data for applying to the more study

  2. Induction and characterization of Arabidopsis mutants by Ion beam

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Y. H.; Choi, J. D.; Park, J. Y.; Lee, J. R.; Sohn, H. S. [Gyeongbuk Institute for Bio Industry, Andong (Korea, Republic of)

    2008-03-15

    This study was conducted to search the proper conditions and times for irradiating proton beam to seeds generally used for induction of mutant. Arabidopsis as model plants has good characters that is a short generation time, producing a lot of seeds, sequenced genome, developed maker. This points were the best materials for plant breeding for this study. The data of inducing mutants of Arabidopsis is used to be applicate to crops have more longer generation that is the final goals of this study. The goals of this project were to inducing and characterizing arabidopsis mutants by the proton ion beam and {gamma}-ray. As well as, the purpose of this study was securing more than 10 lines of arabidopsis mutants in this project and also to know the changed DNA structure of the mutants using the basic data for applying to the more study

  3. Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models

    NARCIS (Netherlands)

    Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A.; Serna-Bolea, Cèlia; van den Blink, Agnes E.; van 't Wout, Angélique B.; Schuitemaker, Hanneke; Suchard, Marc A.

    2011-01-01

    The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically

  4. Characterizing visible and invisible cell wall mutant phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Carpita, Nicholas C.; McCann, Maureen C.

    2015-04-06

    About 10% of a plant's genome is devoted to generating the protein machinery to synthesize, remodel, and deconstruct the cell wall. High-throughput genome sequencing technologies have enabled a reasonably complete inventory of wall-related genes that can be assembled into families of common evolutionary origin. Assigning function to each gene family member has been aided immensely by identification of mutants with visible phenotypes or by chemical and spectroscopic analysis of mutants with ‘invisible’ phenotypes of modified cell wall composition and architecture that do not otherwise affect plant growth or development. This review connects the inference of gene function on the basis of deviation from the wild type in genetic functional analyses to insights provided by modern analytical techniques that have brought us ever closer to elucidating the sequence structures of the major polysaccharide components of the plant cell wall.

  5. Evolutionary public health: introducing the concept.

    Science.gov (United States)

    Wells, Jonathan C K; Nesse, Randolph M; Sear, Rebecca; Johnstone, Rufus A; Stearns, Stephen C

    2017-07-29

    The emerging discipline of evolutionary medicine is breaking new ground in understanding why people become ill. However, the value of evolutionary analyses of human physiology and behaviour is only beginning to be recognised in the field of public health. Core principles come from life history theory, which analyses the allocation of finite amounts of energy between four competing functions-maintenance, growth, reproduction, and defence. A central tenet of evolutionary theory is that organisms are selected to allocate energy and time to maximise reproductive success, rather than health or longevity. Ecological interactions that influence mortality risk, nutrient availability, and pathogen burden shape energy allocation strategies throughout the life course, thereby affecting diverse health outcomes. Public health interventions could improve their own effectiveness by incorporating an evolutionary perspective. In particular, evolutionary approaches offer new opportunities to address the complex challenges of global health, in which populations are differentially exposed to the metabolic consequences of poverty, high fertility, infectious diseases, and rapid changes in nutrition and lifestyle. The effect of specific interventions is predicted to depend on broader factors shaping life expectancy. Among the important tools in this approach are mathematical models, which can explore probable benefits and limitations of interventions in silico, before their implementation in human populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The evolutionary ecology of molecular replicators.

    Science.gov (United States)

    Nee, Sean

    2016-08-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

  7. Evolutionary accounts of human behavioural diversity

    Science.gov (United States)

    Brown, Gillian R.; Dickins, Thomas E.; Sear, Rebecca; Laland, Kevin N.

    2011-01-01

    Human beings persist in an extraordinary range of ecological settings, in the process exhibiting enormous behavioural diversity, both within and between populations. People vary in their social, mating and parental behaviour and have diverse and elaborate beliefs, traditions, norms and institutions. The aim of this theme issue is to ask whether, and how, evolutionary theory can help us to understand this diversity. In this introductory article, we provide a background to the debate surrounding how best to understand behavioural diversity using evolutionary models of human behaviour. In particular, we examine how diversity has been viewed by the main subdisciplines within the human evolutionary behavioural sciences, focusing in particular on the human behavioural ecology, evolutionary psychology and cultural evolution approaches. In addition to differences in focus and methodology, these subdisciplines have traditionally varied in the emphasis placed on human universals, ecological factors and socially learned behaviour, and on how they have addressed the issue of genetic variation. We reaffirm that evolutionary theory provides an essential framework for understanding behavioural diversity within and between human populations, but argue that greater integration between the subfields is critical to developing a satisfactory understanding of diversity. PMID:21199836

  8. Observational and evolutionary aspects of Wolf-Rayet stars

    International Nuclear Information System (INIS)

    Vanbeveren, D.

    1980-01-01

    The author considers (i) the binary status of Wolf-Rayet stars, (ii) the evolutionary status of Wolf-Rayet stars, (iii) the chemical abundances of Wolf-Rayet stars and (iv) evolutionary models for some known Wolf-Rayet systems. (G.T.H.)

  9. Evolutionary optimization of production materials workflow processes

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Hansen, Zaza Nadja Lee; Jacobsen, Peter

    2014-01-01

    We present an evolutionary optimisation technique for stochastic production processes, which is able to find improved production materials workflow processes with respect to arbitrary combinations of numerical quantities associated with the production process. Working from a core fragment...... of the BPMN language, we employ an evolutionary algorithm where stochastic model checking is used as a fitness function to determine the degree of improvement of candidate processes derived from the original process through mutation and cross-over operations. We illustrate this technique using a case study...

  10. Genomes, Phylogeny, and Evolutionary Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  11. Evolutionary potential games on lattices

    International Nuclear Information System (INIS)

    Szabó, György; Borsos, István

    2016-01-01

    Game theory provides a general mathematical background to study the effect of pair interactions and evolutionary rules on the macroscopic behavior of multi-player games where players with a finite number of strategies may represent a wide scale of biological objects, human individuals, or even their associations. In these systems the interactions are characterized by matrices that can be decomposed into elementary matrices (games) and classified into four types. The concept of decomposition helps the identification of potential games and also the evaluation of the potential that plays a crucial role in the determination of the preferred Nash equilibrium, and defines the Boltzmann distribution towards which these systems evolve for suitable types of dynamical rules. This survey draws parallel between the potential games and the kinetic Ising type models which are investigated for a wide scale of connectivity structures. We discuss briefly the applicability of the tools and concepts of statistical physics and thermodynamics. Additionally the general features of ordering phenomena, phase transitions and slow relaxations are outlined and applied to evolutionary games. The discussion extends to games with three or more strategies. Finally we discuss what happens when the system is weakly driven out of the “equilibrium state” by adding non-potential components representing games of cyclic dominance.

  12. Evolutionary potential games on lattices

    Energy Technology Data Exchange (ETDEWEB)

    Szabó, György, E-mail: szabo@mfa.kfki.hu; Borsos, István, E-mail: borsos@mfa.kfki.hu

    2016-04-05

    Game theory provides a general mathematical background to study the effect of pair interactions and evolutionary rules on the macroscopic behavior of multi-player games where players with a finite number of strategies may represent a wide scale of biological objects, human individuals, or even their associations. In these systems the interactions are characterized by matrices that can be decomposed into elementary matrices (games) and classified into four types. The concept of decomposition helps the identification of potential games and also the evaluation of the potential that plays a crucial role in the determination of the preferred Nash equilibrium, and defines the Boltzmann distribution towards which these systems evolve for suitable types of dynamical rules. This survey draws parallel between the potential games and the kinetic Ising type models which are investigated for a wide scale of connectivity structures. We discuss briefly the applicability of the tools and concepts of statistical physics and thermodynamics. Additionally the general features of ordering phenomena, phase transitions and slow relaxations are outlined and applied to evolutionary games. The discussion extends to games with three or more strategies. Finally we discuss what happens when the system is weakly driven out of the “equilibrium state” by adding non-potential components representing games of cyclic dominance.

  13. The Evolutionary Puzzle of Suicide

    Directory of Open Access Journals (Sweden)

    Henri-Jean Aubin

    2013-12-01

    Full Text Available Mechanisms of self-destruction are difficult to reconcile with evolution’s first rule of thumb: survive and reproduce. However, evolutionary success ultimately depends on inclusive fitness. The altruistic suicide hypothesis posits that the presence of low reproductive potential and burdensomeness toward kin can increase the inclusive fitness payoff of self-removal. The bargaining hypothesis assumes that suicide attempts could function as an honest signal of need. The payoff may be positive if the suicidal person has a low reproductive potential. The parasite manipulation hypothesis is founded on the rodent—Toxoplasma gondii host-parasite model, in which the parasite induces a “suicidal” feline attraction that allows the parasite to complete its life cycle. Interestingly, latent infection by T. gondii has been shown to cause behavioral alterations in humans, including increased suicide attempts. Finally, we discuss how suicide risk factors can be understood as nonadaptive byproducts of evolved mechanisms that malfunction. Although most of the mechanisms proposed in this article are largely speculative, the hypotheses that we raise accept self-destructive behavior within the framework of evolutionary theory.

  14. Evolutionary potential games on lattices

    Science.gov (United States)

    Szabó, György; Borsos, István

    2016-04-01

    Game theory provides a general mathematical background to study the effect of pair interactions and evolutionary rules on the macroscopic behavior of multi-player games where players with a finite number of strategies may represent a wide scale of biological objects, human individuals, or even their associations. In these systems the interactions are characterized by matrices that can be decomposed into elementary matrices (games) and classified into four types. The concept of decomposition helps the identification of potential games and also the evaluation of the potential that plays a crucial role in the determination of the preferred Nash equilibrium, and defines the Boltzmann distribution towards which these systems evolve for suitable types of dynamical rules. This survey draws parallel between the potential games and the kinetic Ising type models which are investigated for a wide scale of connectivity structures. We discuss briefly the applicability of the tools and concepts of statistical physics and thermodynamics. Additionally the general features of ordering phenomena, phase transitions and slow relaxations are outlined and applied to evolutionary games. The discussion extends to games with three or more strategies. Finally we discuss what happens when the system is weakly driven out of the "equilibrium state" by adding non-potential components representing games of cyclic dominance.

  15. The evolutionary implications of epigenetic inheritance.

    Science.gov (United States)

    Jablonka, Eva

    2017-10-06

    The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

  16. Infrastructure system restoration planning using evolutionary algorithms

    Science.gov (United States)

    Corns, Steven; Long, Suzanna K.; Shoberg, Thomas G.

    2016-01-01

    This paper presents an evolutionary algorithm to address restoration issues for supply chain interdependent critical infrastructure. Rapid restoration of infrastructure after a large-scale disaster is necessary to sustaining a nation's economy and security, but such long-term restoration has not been investigated as thoroughly as initial rescue and recovery efforts. A model of the Greater Saint Louis Missouri area was created and a disaster scenario simulated. An evolutionary algorithm is used to determine the order in which the bridges should be repaired based on indirect costs. Solutions were evaluated based on the reduction of indirect costs and the restoration of transportation capacity. When compared to a greedy algorithm, the evolutionary algorithm solution reduced indirect costs by approximately 12.4% by restoring automotive travel routes for workers and re-establishing the flow of commodities across the three rivers in the Saint Louis area.

  17. Function Follows Performance in Evolutionary Computational Processing

    DEFF Research Database (Denmark)

    Pasold, Anke; Foged, Isak Worre

    2011-01-01

    As the title ‘Function Follows Performance in Evolutionary Computational Processing’ suggests, this paper explores the potentials of employing multiple design and evaluation criteria within one processing model in order to account for a number of performative parameters desired within varied...

  18. Mutants of alfalfa mosaic virus

    International Nuclear Information System (INIS)

    Roosien, J.

    1983-01-01

    In this thesis the isolation and characterization of a number of mutants of alfalfa mosaic virus, a plant virus with a coat protein dependent genome, is described. Thermo-sensitive (ts) mutants were selected since, at least theoretically, ts mutations can be present in all virus coded functions. It was found that a high percentage of spontaneous mutants, isolated because of their aberrant symptoms, were ts. The majority of these isolates could grow at the non-permissive temperature in the presence of a single wild type (wt) component. To increase the mutation rate virus preparations were treated with several mutagens. After nitrous acid treatment or irradiation with ultraviolet light, an increase in the level of mutations was observed. UV irradiation was preferred since it did not require large amounts of purified viral components. During the preliminary characterization of potential ts mutants the author also obtained one structural and several symptom mutants which were analysed further (chapter 7, 8 and 9). The properties of the ts mutants are described in chapter 3-7. (Auth.)

  19. Root hair mutants of barley

    International Nuclear Information System (INIS)

    Engvild, K.C.; Rasmussen, K.

    2005-01-01

    Barley mutants without root hairs or with short or reduced root hairs were isolated among M 2 seeds of 'Lux' barley (Hordeum vulgare L.) after acidified sodium azide mutagenesis. Root hair mutants are investigated intensively in Arabidopsis where about 40 genes are known. A few root hair mutants are known in maize, rice, barley and tomato. Many plants without root hairs grow quite well with good plant nutrition, and mutants have been used for investigations of uptake of strongly bound nutrients like phosphorus, iron, zinc and silicon. Seed of 'Lux' barley (Sejet Plant Breeding, Denmark) were soaked overnight, and then treated with 1.5-millimolarsodium azide in 0.1 molar sodium phosphate buffer, pH 3, for 2.5 hours according to the IAEA Manual on Mutation Breeding (2nd Ed.). After rinsing in tap water and air-drying, the M 2 seeds were sown in the field the same day. Spikes, 4-6 per M 1 plant, were harvested. The mutation frequency was similar to that obtained with other barley cultivars from which low-phytate mutants were isolated [5]. Seeds were germinated on black filter paper in tap water for 3 or 4 days before scoring for root hair mutants

  20. Evolutionary game theory and organizational ecology: The case of resource-partitioning theory

    OpenAIRE

    ZHOU, Chaohong; VAN WITTELOOSTUIJN, Arjen

    2009-01-01

    Abstract: In this paper, we construct a mathematical model that applies tools from evolutionary game theory to issues in organizational ecology. Evolutionary game theory shares the key feature of mathematical rigor with the industrial organization tradition, but is similar to organizational ecology by emphasizing evolutionary dynamics. Evolutionary game theory may well be a complementary modeling tool for the analytical study of organizational ecology issues, next to formal logic, standard ga...

  1. Evolutionary Computation and Its Applications in Neural and Fuzzy Systems

    Directory of Open Access Journals (Sweden)

    Biaobiao Zhang

    2011-01-01

    Full Text Available Neural networks and fuzzy systems are two soft-computing paradigms for system modelling. Adapting a neural or fuzzy system requires to solve two optimization problems: structural optimization and parametric optimization. Structural optimization is a discrete optimization problem which is very hard to solve using conventional optimization techniques. Parametric optimization can be solved using conventional optimization techniques, but the solution may be easily trapped at a bad local optimum. Evolutionary computation is a general-purpose stochastic global optimization approach under the universally accepted neo-Darwinian paradigm, which is a combination of the classical Darwinian evolutionary theory, the selectionism of Weismann, and the genetics of Mendel. Evolutionary algorithms are a major approach to adaptation and optimization. In this paper, we first introduce evolutionary algorithms with emphasis on genetic algorithms and evolutionary strategies. Other evolutionary algorithms such as genetic programming, evolutionary programming, particle swarm optimization, immune algorithm, and ant colony optimization are also described. Some topics pertaining to evolutionary algorithms are also discussed, and a comparison between evolutionary algorithms and simulated annealing is made. Finally, the application of EAs to the learning of neural networks as well as to the structural and parametric adaptations of fuzzy systems is also detailed.

  2. Evolutionary origins and diversification of proteobacterial mutualists.

    Science.gov (United States)

    Sachs, Joel L; Skophammer, Ryan G; Bansal, Nidhanjali; Stajich, Jason E

    2014-01-22

    Mutualistic bacteria infect most eukaryotic species in nearly every biome. Nonetheless, two dilemmas remain unresolved about bacterial-eukaryote mutualisms: how do mutualist phenotypes originate in bacterial lineages and to what degree do mutualists traits drive or hinder bacterial diversification? Here, we reconstructed the phylogeny of the hyperdiverse phylum Proteobacteria to investigate the origins and evolutionary diversification of mutualistic bacterial phenotypes. Our ancestral state reconstructions (ASRs) inferred a range of 34-39 independent origins of mutualist phenotypes in Proteobacteria, revealing the surprising frequency with which host-beneficial traits have evolved in this phylum. We found proteobacterial mutualists to be more often derived from parasitic than from free-living ancestors, consistent with the untested paradigm that bacterial mutualists most often evolve from pathogens. Strikingly, we inferred that mutualists exhibit a negative net diversification rate (speciation minus extinction), which suggests that mutualism evolves primarily via transitions from other states rather than diversification within mutualist taxa. Moreover, our ASRs infer that proteobacterial mutualist lineages exhibit a paucity of reversals to parasitism or to free-living status. This evolutionary conservatism of mutualism is contrary to long-standing theory, which predicts that selection should often favour mutants in microbial mutualist populations that exploit or abandon more slowly evolving eukaryotic hosts.

  3. Form of an evolutionary tradeoff affects eco-evolutionary dynamics in a predator-prey system.

    Science.gov (United States)

    Kasada, Minoru; Yamamichi, Masato; Yoshida, Takehito

    2014-11-11

    Evolution on a time scale similar to ecological dynamics has been increasingly recognized for the last three decades. Selection mediated by ecological interactions can change heritable phenotypic variation (i.e., evolution), and evolution of traits, in turn, can affect ecological interactions. Hence, ecological and evolutionary dynamics can be tightly linked and important to predict future dynamics, but our understanding of eco-evolutionary dynamics is still in its infancy and there is a significant gap between theoretical predictions and empirical tests. Empirical studies have demonstrated that the presence of genetic variation can dramatically change ecological dynamics, whereas theoretical studies predict that eco-evolutionary dynamics depend on the details of the genetic variation, such as the form of a tradeoff among genotypes, which can be more important than the presence or absence of the genetic variation. Using a predator-prey (rotifer-algal) experimental system in laboratory microcosms, we studied how different forms of a tradeoff between prey defense and growth affect eco-evolutionary dynamics. Our experimental results show for the first time to our knowledge that different forms of the tradeoff produce remarkably divergent eco-evolutionary dynamics, including near fixation, near extinction, and coexistence of algal genotypes, with quantitatively different population dynamics. A mathematical model, parameterized from completely independent experiments, explains the observed dynamics. The results suggest that knowing the details of heritable trait variation and covariation within a population is essential for understanding how evolution and ecology will interact and what form of eco-evolutionary dynamics will result.

  4. Studies in evolutionary agroecology

    DEFF Research Database (Denmark)

    Wille, Wibke

    of population performance will increase in frequency. Yield, one of the fundamental agronomic variables, is not an individual, but a population characteristic. A farmer wants a high yield per hectare; he is not interested in the performance of individual plants. When individual selection and population...... of Evolutionary Agroecology that the highest yielding individuals do not necessarily perform best as a population. The investment of resources into strategies and structures increasing individual competitive ability carries a cost. If a whole population consists of individuals investing resources to compete...

  5. Towards Adaptive Evolutionary Architecture

    DEFF Research Database (Denmark)

    Bak, Sebastian HOlt; Rask, Nina; Risi, Sebastian

    2016-01-01

    This paper presents first results from an interdisciplinary project, in which the fields of architecture, philosophy and artificial life are combined to explore possible futures of architecture. Through an interactive evolutionary installation, called EvoCurtain, we investigate aspects of how...... to the development of designs tailored to the individual preferences of inhabitants, changing the roles of architects and designers entirely. Architecture-as-it-could-be is a philosophical approach conducted through artistic methods to anticipate the technological futures of human-centered development within...

  6. Mutants induced in winter rye (Secale cereale L.): Short straw-mutant No. 2714 and late-senescence mutant

    Energy Technology Data Exchange (ETDEWEB)

    Muszynski, S; Darlewska, M [Department of Plant Breeding and Seed Science, Warsaw Agricultural University, Warsaw (Poland)

    1990-01-01

    Full text: Mutants were induced by treating dormant seeds with ionizing radiation (fast neutrons) or chemicals (N-nitroso-N-ethyl urea or sodium azide). Among several mutants obtained, of special value is the short-straw mutant No. 2714 and a late senescent mutant. (author)

  7. Delayed Disease Onset and Extended Survival in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis after Suppression of Mutant SOD1 in the Motor Cortex

    Science.gov (United States)

    Thomsen, Gretchen M.; Gowing, Genevieve; Latter, Jessica; Chen, Maximus; Vit, Jean-Philippe; Staggenborg, Kevin; Avalos, Pablo; Alkaslasi, Mor; Ferraiuolo, Laura; Likhite, Shibi; Kaspar, Brian K.

    2014-01-01

    Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3–5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1G93A rats through targeted delivery of AAV9–SOD1–shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease. PMID:25411487

  8. On Reciprocal Causation in the Evolutionary Process.

    Science.gov (United States)

    Svensson, Erik I

    2018-01-01

    Recent calls for a revision of standard evolutionary theory (SET) are based partly on arguments about the reciprocal causation. Reciprocal causation means that cause-effect relationships are bi-directional, as a cause could later become an effect and vice versa. Such dynamic cause-effect relationships raise questions about the distinction between proximate and ultimate causes, as originally formulated by Ernst Mayr. They have also motivated some biologists and philosophers to argue for an Extended Evolutionary Synthesis (EES). The EES will supposedly expand the scope of the Modern Synthesis (MS) and SET, which has been characterized as gene-centred, relying primarily on natural selection and largely neglecting reciprocal causation. Here, I critically examine these claims, with a special focus on the last conjecture. I conclude that reciprocal causation has l