The rate of beneficial mutations surfing on the wave of a range expansion.

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Rémi Lehe

Full Text Available Many theoretical and experimental studies suggest that range expansions can have severe consequences for the gene pool of the expanding population. Due to strongly enhanced genetic drift at the advancing frontier, neutral and weakly deleterious mutations can reach large frequencies in the newly colonized regions, as if they were surfing the front of the range expansion. These findings raise the question of how frequently beneficial mutations successfully surf at shifting range margins, thereby promoting adaptation towards a range-expansion phenotype. Here, we use individual-based simulations to study the surfing statistics of recurrent beneficial mutations on wave-like range expansions in linear habitats. We show that the rate of surfing depends on two strongly antagonistic factors, the probability of surfing given the spatial location of a novel mutation and the rate of occurrence of mutations at that location. The surfing probability strongly increases towards the tip of the wave. Novel mutations are unlikely to surf unless they enjoy a spatial head start compared to the bulk of the population. The needed head start is shown to be proportional to the inverse fitness of the mutant type, and only weakly dependent on the carrying capacity. The precise location dependence of surfing probabilities is derived from the non-extinction probability of a branching process within a moving field of growth rates. The second factor is the mutation occurrence which strongly decreases towards the tip of the wave. Thus, most successful mutations arise at an intermediate position in the front of the wave. We present an analytic theory for the tradeoff between these factors that allows to predict how frequently substitutions by beneficial mutations occur at invasion fronts. We find that small amounts of genetic drift increase the fixation rate of beneficial mutations at the advancing front, and thus could be important for adaptation during species invasions.

Lineage dynamics and mutation-selection balance in non-adapting asexual populations

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Pénisson, Sophie; Sniegowski, Paul D.; Colato, Alexandre; Gerrish, Philip J.

2013-02-01

In classical population genetics, mutation-selection balance refers to the equilibrium frequency of a deleterious allele established and maintained under two opposing forces: recurrent mutation, which tends to increase the frequency of the allele; and selection, which tends to decrease its frequency. In a haploid population, if μ denotes the per capita rate of production of the deleterious allele by mutation and s denotes the selective disadvantage of carrying the allele, then the classical mutation-selection balance frequency of the allele is approximated by μ/s. This calculation assumes that lineages carrying the mutant allele in question—the ‘focal allele’—do not accumulate deleterious mutations linked to the focal allele. In principle, indirect selection against the focal allele caused by such additional mutations can decrease the frequency of the focal allele below the classical mutation-selection balance. This effect of indirect selection will be strongest in an asexual population, in which the entire genome is in linkage. Here, we use an approach based on a multitype branching process to investigate this effect, analyzing lineage dynamics under mutation, direct selection, and indirect selection in a non-adapting asexual population. We find that the equilibrium balance between recurrent mutation to the focal allele and the forces of direct and indirect selection against the focal allele is closely approximated by γμ/(s + U) (s = 0 if the focal allele is neutral), where γ ≈ eθθ-(ω+θ)(ω + θ)(Γ(ω + θ) - Γ(ω + θ,θ)), \\theta =U/\\tilde {s}, and \\omega =s/\\tilde {s}; U denotes the genomic deleterious mutation rate and \\tilde {s} denotes the geometric mean selective disadvantage of deleterious mutations elsewhere on the genome. This mutation-selection balance for asexual populations can remain surprisingly invariant over wide ranges of the mutation rate.

Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

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Adela M Luján

Full Text Available Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

A new experimental system for study on adaptive mutations

Institute of Scientific and Technical Information of China (English)

Lü; Zhong; (

2001-01-01

［1］Luria, S. E., Delbrück, M., Mutation of bacteria from virus sensitivity to virus resistance, Genetics, 1943, 28: 491.［2］Lederberg, J., Lederberg, E. M., Replica plating and indirect selection of bacteria mutants, J. Bacteriol., 1952, 63: 399.［3］Carins, J., Overbaugh, J., Miller, S., The origin of mutants, Nature, 1988, 355: 142.［4］Foster, P. L., Adaptive mutation: the uses of adversity, Annu. Rev. Microbiol., 1993, 47: 467.［5］Hall, B. G., Adaptive mutagenesis: a process that generates almost exclusively beneficient mutations, Genetica, 1998, 102/103: 109.［6］Kasak, L., Horak, R., Kivisaar, M., Promotor-creating mutations in Psuedmonas putida: A model system for the study of mutation in starving bacteria, PNAS, 1997, 94: 3134.［7］Steele, D. F., Jinks-Robertson, An examination of adaptive reversion in Saccharomyces cerevisiae, Genetics, 1992, 132: 9.［8］Davis, R. W., Botstein, Roth, J. R., Advanced Bacterial Genetics--A Manual for Genetic Engineering, New York: Cold Spring Harbor Laboratory Press, 1980, 13.［9］Miller, J. H., Experiments in Molecular Genetics, New York: Cold Spring Harbor Laboratory Press, 1972, 352.［10］ Lea, D. E., Coulson, C. A., The distribution of the numbers of mutants in bacterial populations, J. Genetics, 1949, 49: 264.［11］ Hughes, K. T., Roth, J. R., Transitory cis complementation: a method for provided transposition function to defective transposons, Genetics, 1988, 119: 9.［12］ Sanderson, K. E., Roth J., Linkage map of Salmonella typhimurium, Microbiol. Rev., 1988, 52: 485.［13］ He, B., Shiau, A., Choi, K. Y., Genes of the E. coli pur region are negatively controlled by a repressor-operator interaction, J. Bacteriol., 1990, 172: 4555.［14］ Liu, B., Huang, Y., Wang, A. Q., Regulation of purine biosynthetic genes expression in Salmonella typhimurium (IV)--Oc mutation site of purG and its function analysis, Science in China, Ser. C, 1997, 40(3): 238.［15］ Tang, H., Qin, J. C., Wang, A. Q

Epistasis increases the rate of conditionally neutral substitution in an adapting population.

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Draghi, Jeremy A; Parsons, Todd L; Plotkin, Joshua B

2011-04-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations--i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations--substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.

Similar rates of protein adaptation in Drosophila miranda and D. melanogaster, two species with different current effective population sizes

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Bachtrog Doris

2008-12-01

Full Text Available Abstract Background Adaptive protein evolution is common in several Drosophila species investigated. Some studies point to very weak selection operating on amino-acid mutations, with average selection intensities on the order of Nes ~ 5 in D. melanogaster and D. simulans. Species with lower effective population sizes should undergo less adaptation since they generate fewer mutations and selection is ineffective on a greater proportion of beneficial mutations. Results Here I study patterns of polymorphism and divergence at 91 X-linked loci in D. miranda, a species with a roughly 5-fold smaller effective population size than D. melanogaster. Surprisingly, I find a similar fraction of amino-acid mutations being driven to fixation by positive selection in D. miranda and D. melanogaster. Genes with higher rates of amino-acid evolution show lower levels of neutral diversity, a pattern predicted by recurrent adaptive protein evolution. I fit a hitchhiking model to patterns of polymorphism in D. miranda and D. melanogaster and estimate an order of magnitude higher selection coefficients for beneficial mutations in D. miranda. Conclusion This analysis suggests that effective population size may not be a major determinant in rates of protein adaptation. Instead, adaptation may not be mutation-limited, or the distribution of fitness effects for beneficial mutations might differ vastly between different species or populations. Alternative explanation such as biases in estimating the fraction of beneficial mutations or slightly deleterious mutation models are also discussed.

Evidence that adaptation in Drosophila is not limited by mutation at single sites.

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Talia Karasov

2010-06-01

Full Text Available Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes. This view is difficult to reconcile, however, with the observation that adaptation to anthropogenic changes, such as the introduction of pesticides, can occur very rapidly. Here we investigate adaptation at a key insecticide resistance locus (Ace in Drosophila melanogaster and show that multiple simple and complex resistance alleles evolved quickly and repeatedly within individual populations. Our results imply that the current effective population size of modern D. melanogaster populations is likely to be substantially larger (> or = 100-fold than commonly believed. This discrepancy arises because estimates of the effective population size are generally derived from levels of standing variation and thus reveal long-term population dynamics dominated by sharp--even if infrequent--bottlenecks. The short-term effective population sizes relevant for strong adaptation, on the other hand, might be much closer to census population sizes. Adaptation in Drosophila may therefore not be limited by waiting for mutations at single sites, and complex adaptive alleles can be generated quickly without fixation of intermediate states. Adaptive events should also commonly involve the simultaneous rise in frequency of independently generated adaptive mutations. These so-called soft sweeps have very distinct effects on the linked neutral polymorphisms compared to the standard hard sweeps in mutation-limited scenarios. Methods for the mapping of adaptive mutations or association mapping of evolutionarily relevant mutations may thus need to be reconsidered.

A self-adaptive genetic algorithm to estimate JA model parameters considering minor loops

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Lu, Hai-liang; Wen, Xi-shan; Lan, Lei; An, Yun-zhu; Li, Xiao-ping

2015-01-15

A self-adaptive genetic algorithm for estimating Jiles–Atherton (JA) magnetic hysteresis model parameters is presented. The fitness function is established based on the distances between equidistant key points of normalized hysteresis loops. Linearity function and logarithm function are both adopted to code the five parameters of JA model. Roulette wheel selection is used and the selection pressure is adjusted adaptively by deducting a proportional which depends on current generation common value. The Crossover operator is established by combining arithmetic crossover and multipoint crossover. Nonuniform mutation is improved by adjusting the mutation ratio adaptively. The algorithm is used to estimate the parameters of one kind of silicon-steel sheet’s hysteresis loops, and the results are in good agreement with published data. - Highlights: • We present a method to find JA parameters for both major and minor loops. • Fitness function is based on distances between key points of normalized loops. • The selection pressure is adjusted adaptively based on generations.

A self-adaptive genetic algorithm to estimate JA model parameters considering minor loops

International Nuclear Information System (INIS)

Lu, Hai-liang; Wen, Xi-shan; Lan, Lei; An, Yun-zhu; Li, Xiao-ping

2015-01-01

A self-adaptive genetic algorithm for estimating Jiles–Atherton (JA) magnetic hysteresis model parameters is presented. The fitness function is established based on the distances between equidistant key points of normalized hysteresis loops. Linearity function and logarithm function are both adopted to code the five parameters of JA model. Roulette wheel selection is used and the selection pressure is adjusted adaptively by deducting a proportional which depends on current generation common value. The Crossover operator is established by combining arithmetic crossover and multipoint crossover. Nonuniform mutation is improved by adjusting the mutation ratio adaptively. The algorithm is used to estimate the parameters of one kind of silicon-steel sheet’s hysteresis loops, and the results are in good agreement with published data. - Highlights: • We present a method to find JA parameters for both major and minor loops. • Fitness function is based on distances between key points of normalized loops. • The selection pressure is adjusted adaptively based on generations

Sexual selection, germline mutation rate and sperm competition

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Møller AP

2003-04-01

Full Text Available Abstract Background An important component of sexual selection arises because females obtain viability benefits for their offspring from their mate choice. Females choosing extra-pair fertilization generally favor males with exaggerated secondary sexual characters, and extra-pair paternity increases the variance in male reproductive success. Furthermore, females are assumed to benefit from 'good genes' from extra-pair sires. How additive genetic variance in such viability genes is maintained despite strong directional selection remains an evolutionary enigma. We propose that sexual selection is associated with elevated mutation rates, changing the balance between mutation and selection, thereby increasing variance in fitness and hence the benefits to be obtained from good genes sexual selection. Two hypotheses may account for such elevated mutation: (1 Increased sperm production associated with sperm competition may increase mutation rate. (2 Mutator alleles increase mutation rates that are revealed by the expression of condition-dependent secondary sexual characters used by choosy females during their mate choice. M Petrie has independently developed the idea that mutator alleles may account for the maintenance of genetic variation in viability despite strong directional selection. Results A comparative study of birds revealed a positive correlation between mutation rate at minisatellite loci and extra-pair paternity, but not between mutation rate and relative testes mass which is a measure of relative sperm production. Minisatellite mutation rates were not related to longevity, suggesting a meiotic rather than a mitotic origin of mutations. Conclusion We found evidence of increased mutation rate in species with more intense sexual selection. Increased mutation was not associated with increased sperm production, and we suggest that species with intense sexual selection may maintain elevated mutation rates because sexual selection continuously

Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria.

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Frenoy, Antoine; Bonhoeffer, Sebastian

2018-05-01

The stress-induced mutagenesis hypothesis postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to better withstand the stress. This has implications for antibiotic treatment: exposure to subinhibitory doses of antibiotics has been reported to increase bacterial mutation rates and thus probably the rate at which resistance mutations appear and lead to treatment failure. More generally, the hypothesis posits that stress increases evolvability (the ability of a population to generate adaptive genetic diversity) and thus accelerates evolution. Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet subinhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus providing more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress. We developed a system based on plasmid segregation that allows us to measure death and division rates simultaneously in bacterial populations. Using this system, we found that a substantial death rate occurs at the tested subinhibitory concentrations previously reported to increase mutation rate. Taking this death rate into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover, even when antibiotics increase mutation rate, we show that subinhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics. We conclude that antibiotic-induced mutagenesis is overestimated because of death and that understanding evolvability under stress requires accounting for the effects of stress on population dynamics as much as on mutation rate. Our goal here is dual: we show that population dynamics and, in particular, the

Avoiding dangerous missense: thermophiles display especially low mutation rates.

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John W Drake

2009-06-01

Full Text Available Rates of spontaneous mutation have been estimated under optimal growth conditions for a variety of DNA-based microbes, including viruses, bacteria, and eukaryotes. When expressed as genomic mutation rates, most of the values were in the vicinity of 0.003-0.004 with a range of less than two-fold. Because the genome sizes varied by roughly 10(4-fold, the mutation rates per average base pair varied inversely by a similar factor. Even though the commonality of the observed genomic rates remains unexplained, it implies that mutation rates in unstressed microbes reach values that can be finely tuned by evolution. An insight originating in the 1920s and maturing in the 1960s proposed that the genomic mutation rate would reflect a balance between the deleterious effect of the average mutation and the cost of further reducing the mutation rate. If this view is correct, then increasing the deleterious impact of the average mutation should be countered by reducing the genomic mutation rate. It is a common observation that many neutral or nearly neutral mutations become strongly deleterious at higher temperatures, in which case they are called temperature-sensitive mutations. Recently, the kinds and rates of spontaneous mutations were described for two microbial thermophiles, a bacterium and an archaeon. Using an updated method to extrapolate from mutation-reporter genes to whole genomes reveals that the rate of base substitutions is substantially lower in these two thermophiles than in mesophiles. This result provides the first experimental support for the concept of an evolved balance between the total genomic impact of mutations and the cost of further reducing the basal mutation rate.

Reciprocal sign epistasis between frequently experimentally evolved adaptive mutations causes a rugged fitness landscape.

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Daniel J Kvitek

2011-04-01

Full Text Available The fitness landscape captures the relationship between genotype and evolutionary fitness and is a pervasive metaphor used to describe the possible evolutionary trajectories of adaptation. However, little is known about the actual shape of fitness landscapes, including whether valleys of low fitness create local fitness optima, acting as barriers to adaptive change. Here we provide evidence of a rugged molecular fitness landscape arising during an evolution experiment in an asexual population of Saccharomyces cerevisiae. We identify the mutations that arose during the evolution using whole-genome sequencing and use competitive fitness assays to describe the mutations individually responsible for adaptation. In addition, we find that a fitness valley between two adaptive mutations in the genes MTH1 and HXT6/HXT7 is caused by reciprocal sign epistasis, where the fitness cost of the double mutant prohibits the two mutations from being selected in the same genetic background. The constraint enforced by reciprocal sign epistasis causes the mutations to remain mutually exclusive during the experiment, even though adaptive mutations in these two genes occur several times in independent lineages during the experiment. Our results show that epistasis plays a key role during adaptation and that inter-genic interactions can act as barriers between adaptive solutions. These results also provide a new interpretation on the classic Dobzhansky-Muller model of reproductive isolation and display some surprising parallels with mutations in genes often associated with tumors.

Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

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Werner, Benjamin; Sottoriva, Andrea

2018-06-01

The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

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Benjamin Werner

2018-06-01

Full Text Available The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99. In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88 in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

Codon adaptation and synonymous substitution rate in diatom plastid genes.

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Morton, Brian R; Sorhannus, Ulf; Fox, Martin

2002-07-01

Diatom plastid genes are examined with respect to codon adaptation and rates of silent substitution (Ks). It is shown that diatom genes follow the same pattern of codon usage as other plastid genes studied previously. Highly expressed diatom genes display codon adaptation, or a bias toward specific major codons, and these major codons are the same as those in red algae, green algae, and land plants. It is also found that there is a strong correlation between Ks and variation in codon adaptation across diatom genes, providing the first evidence for such a relationship in the algae. It is argued that this finding supports the notion that the correlation arises from selective constraints, not from variation in mutation rate among genes. Finally, the diatom genes are examined with respect to variation in Ks among different synonymous groups. Diatom genes with strong codon adaptation do not show the same variation in synonymous substitution rate among codon groups as the flowering plant psbA gene which, previous studies have shown, has strong codon adaptation but unusually high rates of silent change in certain synonymous groups. The lack of a similar finding in diatoms supports the suggestion that the feature is unique to the flowering plant psbA due to recent relaxations in selective pressure in that lineage.

Minisatellite germline mutation rate in the Techa River population

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Dubrova, Yuri E. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom)]. E-mail: yed2@le.ac.uk; Ploshchanskaya, Olga G. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation); Kozionova, Olga S. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation); Akleyev, Alexander V. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation)

2006-12-01

Germline mutation at eight minisatellite loci has been studied among the irradiated families from the Techa River population and non-exposed families from the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by ethnicity, parental age, occupation and smoking habit. A statistically significant 1.7-fold increase in mutation rate was found in the germline of irradiated fathers, whereas maternal germline mutation rate in the exposed families was not elevated. Most of the minisatellite loci showed an elevated paternal mutation rate in the exposed group, indicating a generalised increase in minisatellite germline mutation rate in the Techa River population. These data suggest that the elevated minisatellite mutation rate can be attributed to radioactive exposure. The spectra of paternal mutation seen in the unexposed and exposed families were indistinguishable.

Minisatellite germline mutation rate in the Techa River population

International Nuclear Information System (INIS)

Dubrova, Yuri E.; Ploshchanskaya, Olga G.; Kozionova, Olga S.; Akleyev, Alexander V.

2006-01-01

Germline mutation at eight minisatellite loci has been studied among the irradiated families from the Techa River population and non-exposed families from the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by ethnicity, parental age, occupation and smoking habit. A statistically significant 1.7-fold increase in mutation rate was found in the germline of irradiated fathers, whereas maternal germline mutation rate in the exposed families was not elevated. Most of the minisatellite loci showed an elevated paternal mutation rate in the exposed group, indicating a generalised increase in minisatellite germline mutation rate in the Techa River population. These data suggest that the elevated minisatellite mutation rate can be attributed to radioactive exposure. The spectra of paternal mutation seen in the unexposed and exposed families were indistinguishable

Precise estimates of mutation rate and spectrum in yeast

Science.gov (United States)

Zhu, Yuan O.; Siegal, Mark L.; Hall, David W.; Petrov, Dmitri A.

2014-01-01

Mutation is the ultimate source of genetic variation. The most direct and unbiased method of studying spontaneous mutations is via mutation accumulation (MA) lines. Until recently, MA experiments were limited by the cost of sequencing and thus provided us with small numbers of mutational events and therefore imprecise estimates of rates and patterns of mutation. We used whole-genome sequencing to identify nearly 1,000 spontaneous mutation events accumulated over ∼311,000 generations in 145 diploid MA lines of the budding yeast Saccharomyces cerevisiae. MA experiments are usually assumed to have negligible levels of selection, but even mild selection will remove strongly deleterious events. We take advantage of such patterns of selection and show that mutation classes such as indels and aneuploidies (especially monosomies) are proportionately much more likely to contribute mutations of large effect. We also provide conservative estimates of indel, aneuploidy, environment-dependent dominant lethal, and recessive lethal mutation rates. To our knowledge, for the first time in yeast MA data, we identified a sufficiently large number of single-nucleotide mutations to measure context-dependent mutation rates and were able to (i) confirm strong AT bias of mutation in yeast driven by high rate of mutations from C/G to T/A and (ii) detect a higher rate of mutation at C/G nucleotides in two specific contexts consistent with cytosine methylation in S. cerevisiae. PMID:24847077

Experimental evolution and the dynamics of genomic mutation rate modifiers.

Science.gov (United States)

Raynes, Y; Sniegowski, P D

2014-11-01

Because genes that affect mutation rates are themselves subject to mutation, mutation rates can be influenced by natural selection and other evolutionary forces. The population genetics of mutation rate modifier alleles has been a subject of theoretical interest for many decades. Here, we review experimental contributions to our understanding of mutation rate modifier dynamics. Numerous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic mutation rate) can readily rise to high frequencies via genetic hitchhiking in non-recombining microbial populations. Whereas these results certainly provide an explanatory framework for observations of sporadically high mutation rates in pathogenic microbes and in cancer lineages, it is nonetheless true that most natural populations have very low mutation rates. This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effect reversed in natural populations. Very little experimental work has addressed this question; with this in mind, we identify some promising areas for future experimental investigation.

Complete-proteome mapping of human influenza A adaptive mutations: implications for human transmissibility of zoonotic strains.

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Miotto, Olivo; Heiny, A T; Albrecht, Randy; García-Sastre, Adolfo; Tan, Tin Wee; August, J Thomas; Brusic, Vladimir

2010-02-03

There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear

Evolution and Adaptation in Pseudomonas aeruginosa Biofilms Driven by Mismatch Repair System-Deficient Mutators

DEFF Research Database (Denmark)

Luján, Adela M.; Maciá, María D.; Yang, Liang

2011-01-01

, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic...... infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition...... diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution...

Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

International Nuclear Information System (INIS)

Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H.; Herrmann, Andreas

2016-01-01

The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA_1 D130E, HA_2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

2016-05-15

The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

Adaptive Mutations in Influenza A/California/07/2009 Enhance Polymerase Activity and Infectious Virion Production

Science.gov (United States)

Slaine, Patrick D.; MacRae, Cara; Kleer, Mariel; Lamoureux, Emily; McAlpine, Sarah; Warhuus, Michelle; Comeau, André M.; Hatchette, Todd

2018-01-01

Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (also known as CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments. Among mutations that emerged during mouse-adaptation, we focused on amino acid substitutions in polymerase subunits: polymerase basic-1 (PB1) T156A and F740L and polymerase acidic (PA) E349G. These mutations were evaluated singly and in combination in minigenome replicon assays, which revealed that PA E349G increased polymerase activity. By selectively engineering three PB1 and PA mutations into the parental CA/07 strain, we demonstrated that these mutations in polymerase subunits decreased the production of defective viral genome segments with internal deletions and dramatically increased the release of infectious virions from mouse cells. Together, these findings increase our understanding of the contribution of polymerase subunits to successful host adaptation. PMID:29783694

Adaptive benefits from small mutation supplies in an antibiotic resistance enzyme

NARCIS (Netherlands)

Salverda, Merijn L.M.; Koomen, Jeroen; Koopmanschap, Bertha; Zwart, Mark P.; Visser, De J.A.G.M.

2017-01-01

Populations with large mutation supplies adapt via the “greedy” substitution of the fittest genotype available, leading to fast and repeatable short-term responses. At longer time scales, smaller mutation supplies may in theory lead to larger improvements when distant high-fitness genotypes more

A Constant Rate of Spontaneous Mutation in DNA-Based Microbes

Science.gov (United States)

Drake, John W.

1991-08-01

In terms of evolution and fitness, the most significant spontaneous mutation rate is likely to be that for the entire genome (or its nonfrivolous fraction). Information is now available to calculate this rate for several DNA-based haploid microbes, including bacteriophages with single- or double-stranded DNA, a bacterium, a yeast, and a filamentous fungus. Their genome sizes vary by ≈6500-fold. Their average mutation rates per base pair vary by ≈16,000-fold, whereas their mutation rates per genome vary by only ≈2.5-fold, apparently randomly, around a mean value of 0.0033 per DNA replication. The average mutation rate per base pair is inversely proportional to genome size. Therefore, a nearly invariant microbial mutation rate appears to have evolved. Because this rate is uniform in such diverse organisms, it is likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs of further reducing mutation rates.

Monotonicity of fitness landscapes and mutation rate control.

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Belavkin, Roman V; Channon, Alastair; Aston, Elizabeth; Aston, John; Krašovec, Rok; Knight, Christopher G

2016-12-01

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms.

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

DEFF Research Database (Denmark)

Bailey, Susan; Hinz, Aaron; Kassen, Rees

2014-01-01

Conventional wisdom holds that synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have no detectable effect on phenotype or fitness. However, a growing body of evidence from both comparative and experimental studies suggests otherwise. Synonymous mutations have been...... shown to impact gene expression, protein folding and fitness, however, direct evidence that they can be positively selected, and so contribute to adaptation, is lacking. Here we report the recovery of two beneficial synonymous single base pair changes that arose spontaneously and independently...... in an experimentally evolved population of Pseudomonas fluorescens. We show experimentally that these mutations increase fitness by an amount comparable to non-synonymous mutations and that the fitness increases stem from increased gene expression. These results provide unequivocal evidence that synonymous mutations...

The effect of self-distancing on adaptive versus maladaptive self-reflection in children.

Science.gov (United States)

Kross, Ethan; Duckworth, Angela; Ayduk, Ozlem; Tsukayama, Eli; Mischel, Walter

2011-10-01

Although children and adolescents vary in their chronic tendencies to adaptively versus maladaptively reflect over negative feelings, the psychological mechanisms underlying these different types of self-reflection among youngsters are unknown. We addressed this issue in the present research by examining the role that self-distancing plays in distinguishing adaptive versus maladaptive self-reflection among an ethnically and socioeconomically diverse sample of fifth-grade public schoolchildren. Children were randomly assigned to analyze their feelings surrounding a recent anger-related interpersonal experience from either a self-immersed or self-distanced perspective. They then rated their negative affect and described in writing the stream of thoughts they experienced when they analyzed their feelings. Children's stream-of-thought essays were content analyzed for the presence of recounting statements, reconstruing statements, and blame attributions. Path analyses indicated that children who analyzed their feelings from a self-distanced perspective focused significantly less on recounting the "hot," emotionally arousing features of their memory (i.e., what happened to me?) and relatively more on reconstruing their experience. This shift in thought content--less recounting and more reconstruing--led children in the self-distanced group to blame the other person involved in their recalled experience significantly less, which in turn led them to display significantly lower levels of emotional reactivity. These findings help delineate the psychological mechanisms that distinguish adaptive versus maladaptive forms of self-reflection over anger experiences in children. Their basic findings and clinical implications are discussed.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

Science.gov (United States)

Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

2015-07-01

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

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Toshihiko Kishimoto

2015-07-01

Full Text Available The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

Spontaneous Self-Distancing and Adaptive Self-Reflection Across Adolescence.

Science.gov (United States)

White, Rachel E; Kross, Ethan; Duckworth, Angela L

2015-07-01

Experiments performed primarily with adults show that self-distancing facilitates adaptive self-reflection. However, no research has investigated whether adolescents spontaneously engage in this process or whether doing so is linked to adaptive outcomes. In this study, 226 African American adolescents, aged 11-20, reflected on an anger-related interpersonal experience. As expected, spontaneous self-distancing during reflection predicted lower levels of emotional reactivity by leading adolescents to reconstrue (rather than recount) their experience and blame their partner less. Moreover, the inverse relation between self-distancing and emotional reactivity strengthened with age. These findings highlight the role that self-distancing plays in fostering adaptive self-reflection in adolescence, and begin to elucidate the role that development plays in enhancing the benefits of engaging in this process. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

[Self-acceptance as adaptively resigning the self to low self-evaluation].

Science.gov (United States)

Ueda, T

1996-10-01

In past studies, the concept of self-acceptance has often been confused with self-evaluation or self-esteem. The purpose of this study was to distinguish these concepts, and operationally define self-acceptance as Carl Rogers proposed: feeling all right toward the self when self-evaluation was low. Self-acceptance as adaptive resignation, a moderating variable, therefore should raise self-esteem of only those people with low self-evaluation. Self-acceptance was measured in the study as affirmative evaluation of own self-evaluation. Two hundred and forty college students, 120 each for men and women, completed a questionnaire of self-evaluative consciousness and self-esteem scales. Results of statistical analyses showed that among subjects with low self-evaluation, the higher self-acceptance, the higher the person's self-esteem. The same relation was not observed among those with high self-evaluation. Thus, it may be concluded that self-acceptance was adaptive resignation, and therefore meaningful to only those with low self-evaluation.

Estimating the Per-Base-Pair Mutation Rate in the Yeast Saccharomyces cerevisiae

OpenAIRE

Lang, Gregory I.; Murray, Andrew W.

2008-01-01

Although mutation rates are a key determinant of the rate of evolution they are difficult to measure precisely and global mutations rates (mutations per genome per generation) are often extrapolated from the per-base-pair mutation rate assuming that mutation rate is uniform across the genome. Using budding yeast, we describe an improved method for the accurate calculation of mutation rates based on the fluctuation assay. Our analysis suggests that the per-base-pair mutation rates at two genes...

Studies of human mutation rates: Progress report

International Nuclear Information System (INIS)

Neel, J.V.

1988-01-01

Progress was recorded between January 1 and July 1, 1987 on a project entitled ''Studies of Human Mutation Rates''. Studies underway include methodology for studying mutation at the DNA level, algorithms for automated analyses of two-dimensional polyacrylamide DNA gels, theoretical and applied population genetics, and studies of mutation frequency in A-bomb survivors

Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

Science.gov (United States)

Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N

2015-01-01

Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polζ appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.

Functional Characterization of Adaptive Mutations during the West African Ebola Virus Outbreak.

Science.gov (United States)

Dietzel, Erik; Schudt, Gordian; Krähling, Verena; Matrosovich, Mikhail; Becker, Stephan

2017-01-15

The Ebola virus (EBOV) outbreak in West Africa started in December 2013, claimed more than 11,000 lives, threatened to destabilize a whole region, and showed how easily health crises can turn into humanitarian disasters. EBOV genomic sequences of the West African outbreak revealed nonsynonymous mutations, which induced considerable public attention, but their role in virus spread and disease remains obscure. In this study, we investigated the functional significance of three nonsynonymous mutations that emerged early during the West African EBOV outbreak. Almost 90% of more than 1,000 EBOV genomes sequenced during the outbreak carried the signature of three mutations: a D759G substitution in the active center of the L polymerase, an A82V substitution in the receptor binding domain of surface glycoprotein GP, and an R111C substitution in the self-assembly domain of RNA-encapsidating nucleoprotein NP. Using a newly developed virus-like particle system and reverse genetics, we found that the mutations have an impact on the functions of the respective viral proteins and on the growth of recombinant EBOVs. The mutation in L increased viral transcription and replication, whereas the mutation in NP decreased viral transcription and replication. The mutation in the receptor binding domain of the glycoprotein GP improved the efficiency of GP-mediated viral entry into target cells. Recombinant EBOVs with combinations of the three mutations showed a growth advantage over the prototype isolate Makona C7 lacking the mutations. This study showed that virus variants with improved fitness emerged early during the West African EBOV outbreak. The dimension of the Ebola virus outbreak in West Africa was unprecedented. Amino acid substitutions in the viral L polymerase, surface glycoprotein GP, and nucleocapsid protein NP emerged, were fixed early in the outbreak, and were found in almost 90% of the sequences. Here we showed that these mutations affected the functional activity of

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

International Nuclear Information System (INIS)

Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

2016-01-01

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

Energy Technology Data Exchange (ETDEWEB)

Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

2016-04-15

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

Variation in RNA virus mutation rates across host cells.

Directory of Open Access Journals (Sweden)

Marine Combe

2014-01-01

Full Text Available It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10(-6 to 10(-4 substitutions per nucleotide per round of copying (s/n/r and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV, which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx. 10(-5 s/n/r. Cell immortalization through p53 inactivation and oxygen levels (1-21% did not have a significant impact on viral replication fidelity. This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions. Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells. This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature.

Estimating spontaneous mutation rates at enzyme loci in Drosophila melanogaster

International Nuclear Information System (INIS)

Mukai, Terumi; Yamazaki, Tsuneyuki; Harada, Ko; Kusakabe, Shin-ichi

1990-04-01

Spontaneous mutations were accumulated for 1,620,826 allele-generations on chromosomes that originated from six stem second chromosomes of Drosophila melanogaster. Only null-electromorph mutations were detected. Band-electromorph mutations were not found. The average rate of null-electromorph mutations was 2.71 x 10 -5 per locus per generation. The 95% confidence interval (μ n ) was 1.97 x 10 -5 n -5 per locus per generation. The upper 95% confidence limit of the band-electromorph mutation rate (μ B ) was 2.28 x 10 -6 per locus per generation. It appeared that null mutations were induced by movable genetic elements and that the mutation rates were different from chromosome to chromosome. (author)

Evolutionary invasion and escape in the presence of deleterious mutations.

Directory of Open Access Journals (Sweden)

Claude Loverdo

Full Text Available Replicators such as parasites invading a new host species, species invading a new ecological niche, or cancer cells invading a new tissue often must mutate to adapt to a new environment. It is often argued that a higher mutation rate will favor evolutionary invasion and escape from extinction. However, most mutations are deleterious, and even lethal. We study the probability that the lineage will survive and invade successfully as a function of the mutation rate when both the initial strain and an adaptive mutant strain are threatened by lethal mutations. We show that mutations are beneficial, i.e. a non-zero mutation rate increases survival compared to the limit of no mutations, if in the no-mutation limit the survival probability of the initial strain is smaller than the average survival probability of the strains which are one mutation away. The mutation rate that maximizes survival depends on the characteristics of both the initial strain and the adaptive mutant, but if one strain is closer to the threshold governing survival then its properties will have greater influence. These conclusions are robust for more realistic or mechanistic depictions of the fitness landscapes such as a more detailed viral life history, or non-lethal deleterious mutations.

Resident Ratings of Communication Skills Using the Kalamazoo Adapted Checklist.

Science.gov (United States)

Porcerelli, John H; Brennan, Simone; Carty, Jennifer; Ziadni, Maisa; Markova, Tsveti

2015-09-01

The Kalamazoo Essential Elements Communication Checklist-Adapted (KEECC-A) is a well-regarded instrument for evaluating communication and interpersonal skills. To date, little research has been conducted that assesses the accuracy of resident self-ratings of their communication skills. To assess whether residents can accurately self-rate communication skills, using the KEECC-A, during an objective structured clinical examination (OSCE). A group of 104 residents from 8 specialties completed a multistation OSCE as part of an institutional communication skills curriculum conducted at a single institution. Standardized patients (SPs) and observers were trained in rating communication skills using the KEECC-A. Standardized patient ratings and resident self-ratings were completed immediately following each OSCE encounter, and trained observers rated archived videotapes of the encounters. Resident self-ratings and SP ratings using the KEECC-A were significantly correlated (r104  = 0.238, P = .02), as were resident self-ratings and observer ratings (r104  = 0.284, P = .004). The correlation between the SP ratings and observer (r104  = 0.378, P = .001) ratings were larger in magnitude, but not significantly different (P > .05) from resident/SP or resident/observer correlations. The results suggest that residents, with a modicum of training using the KEECC-A, can accurately rate their own communication and interpersonal skills during an OSCE. Using trained observers to rate resident communication skills provides a unique opportunity for evaluating SP and resident self-ratings. Our findings also lend further support for the reliability and validity of the KEECC-A.

An evolutionary reduction principle for mutation rates at multiple Loci.

Science.gov (United States)

Altenberg, Lee

2011-06-01

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (Evolutionary Biology, vol. 14, pp. 61-204, 1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models.A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface-a generalization of the hyperplane found by Zhivotovsky et al. (Proc. Natl. Acad. Sci. USA 91, 1079-1083, 1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance.Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.

How much do we know about spontaneous human mutation rates

Energy Technology Data Exchange (ETDEWEB)

Crow, J.F. (Univ. of Wisconsin, Madison, WI (United States))

1993-01-01

The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes on the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm and may be considerably higher. The great mutation load implied by a rate of [approx] 1 per zygote can be greatly ameliorated by quasi-transition selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10[sup 2] new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophilia shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations. 31 refs., 3 figs., 2 tabs.

Mutation Rates of STR Systems in Danes

DEFF Research Database (Denmark)

Andersen, Kim Emil; Bøttcher, Susanne Gammelgaard; Christensen, Susanne

Danish paternity cases in the period 1999 to 2005 were investigated regarding mutation rates in STR loci. STR-typing was performed by the Applied Biosystems AmplfStr Profiler Plus kit in the period 1999 to early 2005, hereafter named the PP9, and by Applied Biosystems AmplfStr Identifier kit for ...... and kits. Sex and STR locus specific mutation rates were estimated with 95% confidence limits by the method of Clopper and Pearson (1934)....

Self-rumination, self-reflection, and depression: self-rumination counteracts the adaptive effect of self-reflection.

Science.gov (United States)

Takano, Keisuke; Tanno, Yoshihiko

2009-03-01

Self-focused attention has adaptive and maladaptive aspects: self-reflection and self-rumination [Trapnell, P. D., & Campbell, J. D. (1999). Private self-consciousness and the Five-Factor Model of personality: distinguishing rumination from reflection. Journal of Personality and Social Psychology, 76, 284-304]. Although reflection is thought to be associated with problem solving and the promotion of mental health, previous researches have shown that reflection does not always have an adaptive effect on depression. Authors have examined the causes behind this inconsistency by modeling the relationships among self-reflection, self-rumination, and depression. One hundred and eleven undergraduates (91 men and 20 women) participated in a two-time point assessment with a 3-week interval. Statistical analysis with structural equation modeling showed that self-reflection significantly predicted self-rumination, whereas self-rumination did not predict self-reflection. With regard to depression, self-reflection was associated with a lower level of depression; self-rumination, with a higher level of depression. The total effect of self-reflection on depression was almost zero. This result indicates that self-reflection per se has an adaptive effect, which is canceled out by the maladaptive effect of self-rumination, because reflectors are likely to ruminate and reflect simultaneously.

The potential for induction of autoimmune disease by a randomly-mutated self-antigen

DEFF Research Database (Denmark)

Pedersen, Anders Elm

2007-01-01

-antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto......, a relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self......-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead...

A novel pseudoderivative-based mutation operator for real-coded adaptive genetic algorithms [v2; ref status: indexed, http://f1000r.es/1td

Directory of Open Access Journals (Sweden)

Maxinder S Kanwal

2013-11-01

Full Text Available Recent development of large databases, especially those in genetics and proteomics, is pushing the development of novel computational algorithms that implement rapid and accurate search strategies. One successful approach has been to use artificial intelligence and methods, including pattern recognition (e.g. neural networks and optimization techniques (e.g. genetic algorithms. The focus of this paper is on optimizing the design of genetic algorithms by using an adaptive mutation rate that is derived from comparing the fitness values of successive generations. We propose a novel pseudoderivative-based mutation rate operator designed to allow a genetic algorithm to escape local optima and successfully continue to the global optimum. Once proven successful, this algorithm can be implemented to solve real problems in neurology and bioinformatics. As a first step towards this goal, we tested our algorithm on two 3-dimensional surfaces with multiple local optima, but only one global optimum, as well as on the N-queens problem, an applied problem in which the function that maps the curve is implicit. For all tests, the adaptive mutation rate allowed the genetic algorithm to find the global optimal solution, performing significantly better than other search methods, including genetic algorithms that implement fixed mutation rates.

Teaching the fluctuation test in silico by using mutate: a program to distinguish between the adaptive and spontaneous mutation hypotheses.

Science.gov (United States)

Carvajal-Rodríguez, Antonio

2012-07-01

Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary aspects of current genetics such as sequence databases, DNA mutations, and hypothesis testing, while introducing the fluctuation test. This seminal experiment was originally performed studying Escherichia coli resistance to the infection by bacteriophage T1. The fluctuation test initiated the modern bacterial genetics that 25 years later ushered in the era of the recombinant DNA. Nowadays we know that some deletions in fhuA, the gene responsible for E. coli membrane receptor of T1, could cause the E. coli resistance to this phage. For the sake of simplicity, we will introduce the assumption that a single mutation generates the resistance to T1. During the practical, the students use the program to download some fhuA gene sequences, manually introduce some stop codon mutations, and design a fluctuation test to obtain data for distinguishing between preadaptative (spontaneous) and induced (adaptive) mutation hypotheses. The program can be launched from a browser or, if preferred, its executable file can be downloaded from http://webs.uvigo.es/acraaj/MutateWeb/Mutate.html. It requires the Java 5.0 (or higher) Runtime Environment (freely available at http://www.java.com). Copyright © 2012 Wiley Periodicals, Inc.

The adaptation rate of a quantitative trait in an environmental gradient

Science.gov (United States)

Hermsen, R.

2016-12-01

The spatial range of a species habitat is generally determined by the ability of the species to cope with biotic and abiotic variables that vary in space. Therefore, the species range is itself an evolvable property. Indeed, environmental gradients permit a mode of evolution in which range expansion and adaptation go hand in hand. This process can contribute to rapid evolution of drug resistant bacteria and viruses, because drug concentrations in humans and livestock treated with antibiotics are far from uniform. Here, we use a minimal stochastic model of discrete, interacting organisms evolving in continuous space to study how the rate of adaptation of a quantitative trait depends on the steepness of the gradient and various population parameters. We discuss analytical results for the mean-field limit as well as extensive stochastic simulations. These simulations were performed using an exact, event-driven simulation scheme that can deal with continuous time-, density- and coordinate-dependent reaction rates and could be used for a wide variety of stochastic systems. The results reveal two qualitative regimes. If the gradient is shallow, the rate of adaptation is limited by dispersion and increases linearly with the gradient slope. If the gradient is steep, the adaptation rate is limited by mutation. In this regime, the mean-field result is highly misleading: it predicts that the adaptation rate continues to increase with the gradient slope, whereas stochastic simulations show that it in fact decreases with the square root of the slope. This discrepancy underscores the importance of discreteness and stochasticity even at high population densities; mean-field results, including those routinely used in quantitative genetics, should be interpreted with care.

The adaptation rate of a quantitative trait in an environmental gradient.

Science.gov (United States)

Hermsen, R

2016-11-30

The spatial range of a species habitat is generally determined by the ability of the species to cope with biotic and abiotic variables that vary in space. Therefore, the species range is itself an evolvable property. Indeed, environmental gradients permit a mode of evolution in which range expansion and adaptation go hand in hand. This process can contribute to rapid evolution of drug resistant bacteria and viruses, because drug concentrations in humans and livestock treated with antibiotics are far from uniform. Here, we use a minimal stochastic model of discrete, interacting organisms evolving in continuous space to study how the rate of adaptation of a quantitative trait depends on the steepness of the gradient and various population parameters. We discuss analytical results for the mean-field limit as well as extensive stochastic simulations. These simulations were performed using an exact, event-driven simulation scheme that can deal with continuous time-, density- and coordinate-dependent reaction rates and could be used for a wide variety of stochastic systems. The results reveal two qualitative regimes. If the gradient is shallow, the rate of adaptation is limited by dispersion and increases linearly with the gradient slope. If the gradient is steep, the adaptation rate is limited by mutation. In this regime, the mean-field result is highly misleading: it predicts that the adaptation rate continues to increase with the gradient slope, whereas stochastic simulations show that it in fact decreases with the square root of the slope. This discrepancy underscores the importance of discreteness and stochasticity even at high population densities; mean-field results, including those routinely used in quantitative genetics, should be interpreted with care.

Radiation in relation to mutation rate, mutational damage and human ill-health

International Nuclear Information System (INIS)

Roberts, P.B.

1976-09-01

The effect of radiation in increasing the frequency of gene mutations is now reasonably understood. We discuss first how an increase in the mutation rate is reflected in the mutational damage expressed in populations. It is shown that the mutational damage, assessed by the loss of fitness in a population or the number of eventual gene extinctions, is equal to the number of new mutations arising per generation or the mutation rate. In a population of stable size, a dose of 1 rem given to 10 6 people leads to roughly 600 gene extinctions when summed over all ensuing generations if the dose is applied to only one generation; this number of extinctions will occur in each succeeding generation if the dose is given to every generation. However, the concept of genetic extinction, although quantifiable, is of limited value in assessing radiation risks since its impact on human ill-health is very speculative. In particular, no estimate can be made of the total cost of effects which are minor in each individual in which they arise, but which, because they are so minor, persist in the population for many generations. The best current estimate is for 14-140 obvious defects in the first few generations following exposure of 10 6 people to a dose of 1 rem. (auth.)

The Role of Item Feedback in Self-Adapted Testing.

Science.gov (United States)

Roos, Linda L.; And Others

1997-01-01

The importance of item feedback in self-adapted testing was studied by comparing feedback and no feedback conditions for computerized adaptive tests and self-adapted tests taken by 363 college students. Results indicate that item feedback is not necessary to realize score differences between self-adapted and computerized adaptive testing. (SLD)

Evolutionary rescue of a parasite population by mutation rate evolution.

Science.gov (United States)

Greenspoon, Philip B; Mideo, Nicole

2017-10-01

The risk of antibiotic resistance evolution in parasites is a major problem for public health. Identifying factors which promote antibiotic resistance evolution is thus a priority in evolutionary medicine. The rate at which new mutations enter the parasite population is one important predictor; however, mutation rate is not necessarily a fixed quantity, as is often assumed, but can itself evolve. Here we explore the possible impacts of mutation rate evolution on the fate of a disease circulating in a host population, which is being treated with drugs, the use of which varies over time. Using an evolutionary rescue framework, we find that mutation rate evolution provides a dramatic increase in the probability that a parasite population survives treatment in only a limited region, while providing little or no advantage in other regions. Both epidemiological features, such as the virulence of infection, and population genetic parameters, such as recombination rate, play important roles in determining the probability of evolutionary rescue and whether mutation rate evolution enhances the probability of evolutionary rescue or not. While efforts to curtail mutation rate evolution in parasites may be worthwhile under some circumstances, our results suggest that this need not always be the case. Copyright © 2017 Elsevier Inc. All rights reserved.

Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus

DEFF Research Database (Denmark)

Russell, Rodney S; Meunier, Jean-Christophe; Takikawa, Shingo

2008-01-01

mutations that were selected during serial passage in Huh-7.5 cells were studied. Recombinant genomes containing all five mutations produced 3-4 logs more infectious virions than did wild type. Neither a coding mutation in NS5A nor a silent mutation in E2 was adaptive, whereas coding mutations in E2, p7......The JFH1 strain of hepatitis C virus (HCV) is unique among HCV isolates, in that the wild-type virus can traverse the entire replication cycle in cultured cells. However, without adaptive mutations, only low levels of infectious virus are produced. In the present study, the effects of five...

Teaching the Fluctuation Test "In Silico" by Using Mutate: A Program to Distinguish between the Adaptive and Spontaneous Mutation Hypotheses

Science.gov (United States)

Carvajal-Rodriguez, Antonio

2012-01-01

Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary…

Studies of human mutation rates, December 1, 1985--November 30, 1986

International Nuclear Information System (INIS)

Neel, J.V.

1985-01-01

This program seeks to quantify native human mutation rates and to determine how man's activities may affect these rates. The program is divided into six tasks, i.e. The American Indian mutation rate, monitoring populations for frequency of mutation by electrophoresis of blood proteins, application of molecular biological approaches to the detection and study of mutational events in human populations, development of two-dimensional electrophoresis for identification of mutant proteins, co-operative program with the Radiation Effects Research Foundation in Hiroshima and Nagasaki, Japan, and statistical problems associated with the estimation of mutation rates. Progress of each of the above tasks is related in detail. (DT)

The erratic mitochondrial clock: variations of mutation rate, not population size, affect mtDNA diversity across birds and mammals

Directory of Open Access Journals (Sweden)

Galtier Nicolas

2009-03-01

Full Text Available Abstract Background During the last ten years, major advances have been made in characterizing and understanding the evolution of mitochondrial DNA, the most popular marker of molecular biodiversity. Several important results were recently reported using mammals as model organisms, including (i the absence of relationship between mitochondrial DNA diversity and life-history or ecological variables, (ii the absence of prominent adaptive selection, contrary to what was found in invertebrates, and (iii the unexpectedly large variation in neutral substitution rate among lineages, revealing a possible link with species maximal longevity. We propose to challenge these results thanks to the bird/mammal comparison. Direct estimates of population size are available in birds, and this group presents striking life-history trait differences with mammals (higher mass-specific metabolic rate and longevity. These properties make birds the ideal model to directly test for population size effects, and to discriminate between competing hypotheses about the causes of substitution rate variation. Results A phylogenetic analysis of cytochrome b third-codon position confirms that the mitochondrial DNA mutation rate is quite variable in birds, passerines being the fastest evolving order. On average, mitochondrial DNA evolves slower in birds than in mammals of similar body size. This result is in agreement with the longevity hypothesis, and contradicts the hypothesis of a metabolic rate-dependent mutation rate. Birds show no footprint of adaptive selection on cytochrome b evolutionary patterns, but no link between direct estimates of population size and cytochrome b diversity. The mutation rate is the best predictor we have of within-species mitochondrial diversity in birds. It partly explains the differences in mitochondrial DNA diversity patterns observed between mammals and birds, previously interpreted as reflecting Hill-Robertson interferences with the W

Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.

Directory of Open Access Journals (Sweden)

Yasuha Arai

2016-04-01

Full Text Available A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.

An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for Wireless Sensor Networks.

Science.gov (United States)

Abba, Sani; Lee, Jeong-A

2015-08-18

We propose an autonomous self-aware and adaptive fault-tolerant routing technique (ASAART) for wireless sensor networks. We address the limitations of self-healing routing (SHR) and self-selective routing (SSR) techniques for routing sensor data. We also examine the integration of autonomic self-aware and adaptive fault detection and resiliency techniques for route formation and route repair to provide resilience to errors and failures. We achieved this by using a combined continuous and slotted prioritized transmission back-off delay to obtain local and global network state information, as well as multiple random functions for attaining faster routing convergence and reliable route repair despite transient and permanent node failure rates and efficient adaptation to instantaneous network topology changes. The results of simulations based on a comparison of the ASAART with the SHR and SSR protocols for five different simulated scenarios in the presence of transient and permanent node failure rates exhibit a greater resiliency to errors and failure and better routing performance in terms of the number of successfully delivered network packets, end-to-end delay, delivered MAC layer packets, packet error rate, as well as efficient energy conservation in a highly congested, faulty, and scalable sensor network.

Parallel Evolution of High-Level Aminoglycoside Resistance in Escherichia coli Under Low and High Mutation Supply Rates

Directory of Open Access Journals (Sweden)

Claudia Ibacache-Quiroga

2018-03-01

Full Text Available Antibiotic resistance is a major concern in public health worldwide, thus there is much interest in characterizing the mutational pathways through which susceptible bacteria evolve resistance. Here we use experimental evolution to explore the mutational pathways toward aminoglycoside resistance, using gentamicin as a model, under low and high mutation supply rates. Our results show that both normo and hypermutable strains of Escherichia coli are able to develop resistance to drug dosages > 1,000-fold higher than the minimal inhibitory concentration for their ancestors. Interestingly, such level of resistance was often associated with changes in susceptibility to other antibiotics, most prominently with increased resistance to fosfomycin. Whole-genome sequencing revealed that all resistant derivatives presented diverse mutations in five common genetic elements: fhuA, fusA and the atpIBEFHAGDC, cyoABCDE, and potABCD operons. Despite the large number of mutations acquired, hypermutable strains did not pay, apparently, fitness cost. In contrast to recent studies, we found that the mutation supply rate mainly affected the speed (tempo but not the pattern (mode of evolution: both backgrounds acquired the mutations in the same order, although the hypermutator strain did it faster. This observation is compatible with the adaptive landscape for high-level gentamicin resistance being relatively smooth, with few local maxima; which might be a common feature among antibiotics for which resistance involves multiple loci.

Polyploidy can drive rapid adaptation in yeast

Science.gov (United States)

Selmecki, Anna M.; Maruvka, Yosef E.; Richmond, Phillip A.; Guillet, Marie; Shoresh, Noam; Sorenson, Amber L.; de, Subhajyoti; Kishony, Roy; Michor, Franziska; Dowell, Robin; Pellman, David

2015-03-01

Polyploidy is observed across the tree of life, yet its influence on evolution remains incompletely understood. Polyploidy, usually whole-genome duplication, is proposed to alter the rate of evolutionary adaptation. This could occur through complex effects on the frequency or fitness of beneficial mutations. For example, in diverse cell types and organisms, immediately after a whole-genome duplication, newly formed polyploids missegregate chromosomes and undergo genetic instability. The instability following whole-genome duplications is thought to provide adaptive mutations in microorganisms and can promote tumorigenesis in mammalian cells. Polyploidy may also affect adaptation independently of beneficial mutations through ploidy-specific changes in cell physiology. Here we perform in vitro evolution experiments to test directly whether polyploidy can accelerate evolutionary adaptation. Compared with haploids and diploids, tetraploids undergo significantly faster adaptation. Mathematical modelling suggests that rapid adaptation of tetraploids is driven by higher rates of beneficial mutations with stronger fitness effects, which is supported by whole-genome sequencing and phenotypic analyses of evolved clones. Chromosome aneuploidy, concerted chromosome loss, and point mutations all provide large fitness gains. We identify several mutations whose beneficial effects are manifest specifically in the tetraploid strains. Together, these results provide direct quantitative evidence that in some environments polyploidy can accelerate evolutionary adaptation.

Coordinated Changes in Mutation and Growth Rates Induced by Genome Reduction

Directory of Open Access Journals (Sweden)

Issei Nishimura

2017-07-01

Full Text Available Genome size is determined during evolution, but it can also be altered by genetic engineering in laboratories. The systematic characterization of reduced genomes provides valuable insights into the cellular properties that are quantitatively described by the global parameters related to the dynamics of growth and mutation. In the present study, we analyzed a small collection of W3110 Escherichia coli derivatives containing either the wild-type genome or reduced genomes of various lengths to examine whether the mutation rate, a global parameter representing genomic plasticity, was affected by genome reduction. We found that the mutation rates of these cells increased with genome reduction. The correlation between genome length and mutation rate, which has been reported for the evolution of bacteria, was also identified, intriguingly, for genome reduction. Gene function enrichment analysis indicated that the deletion of many of the genes encoding membrane and transport proteins play a role in the mutation rate changes mediated by genome reduction. Furthermore, the increase in the mutation rate with genome reduction was highly associated with a decrease in the growth rate in a nutrition-dependent manner; thus, poorer media showed a larger change that was of higher significance. This negative correlation was strongly supported by experimental evidence that the serial transfer of the reduced genome improved the growth rate and reduced the mutation rate to a large extent. Taken together, the global parameters corresponding to the genome, growth, and mutation showed a coordinated relationship, which might be an essential working principle for balancing the cellular dynamics appropriate to the environment.

Self-Adaptive Systems for Machine Intelligence

CERN Document Server

He, Haibo

2011-01-01

This book will advance the understanding and application of self-adaptive intelligent systems; therefore it will potentially benefit the long-term goal of replicating certain levels of brain-like intelligence in complex and networked engineering systems. It will provide new approaches for adaptive systems within uncertain environments. This will provide an opportunity to evaluate the strengths and weaknesses of the current state-of-the-art of knowledge, give rise to new research directions, and educate future professionals in this domain. Self-adaptive intelligent systems have wide application

Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

DEFF Research Database (Denmark)

Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

2011-01-01

Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... (HC-TN and DH6), 1b (DH1 and DH5), and 3a (DBN) isolates, using previously identified adaptive mutations. Introduction of mutations from isolates of the same subtype either led to immediate efficient virus production or accelerated culture adaptation. The DH6 and DH5 recombinants without introduced...... mutations did not adapt to culture. Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W, and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5 core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4 (1b), S52 (3a), and SA13 (5a...

Determining Y-STR mutation rates in deep-routing genealogies: Identification of haplogroup differences.

Science.gov (United States)

Claerhout, Sofie; Vandenbosch, Michiel; Nivelle, Kelly; Gruyters, Leen; Peeters, Anke; Larmuseau, Maarten H D; Decorte, Ronny

2018-05-01

Knowledge of Y-chromosomal short tandem repeat (Y-STR) mutation rates is essential to determine the most recent common ancestor (MRCA) in familial searching or genealogy research. Up to now, locus-specific mutation rates have been extensively examined especially for commercially available forensic Y-STRs, while haplogroup specific mutation rates have not yet been investigated in detail. Through 450 patrilineally related namesakes distributed over 212 deep-rooting genealogies, the individual mutation rates of 42 Y-STR loci were determined, including 27 forensic Y-STR loci from the Yfiler ® Plus kit and 15 additional Y-STR loci (DYS388, DYS426, DYS442, DYS447, DYS454, DYS455, DYS459a/b, DYS549, DYS607, DYS643, DYS724a/b and YCAIIa/b). At least 726 mutations were observed over 148,596 meiosis and individual Y-STR mutation rates varied from 2.83 × 10 -4 to 1.86 × 10 -2 . The mutation rate was significantly correlated with the average allele size, the complexity of the repeat motif sequence and the age of the father. Significant differences in average Y-STR mutations rates were observed when haplogroup 'I & J' (4.03 × 10 -3 mutations/generation) was compared to 'R1b' (5.35 × 10 -3 mutations/generation) and to the overall mutation rate (5.03 × 10 -3 mutations/generation). A difference in allele size distribution was identified as the only cause for these haplogroup specific mutation rates. The haplogroup specific mutation rates were also present within the commercially available Y-STR kits (Yfiler ® , PowerPlex ® Y23 System and Yfiler ® Plus). This observation has consequences for applications where an average Y-STR mutation rate is used, e.g. tMRCA estimations in familial searching and genealogy research. Copyright © 2018 Elsevier B.V. All rights reserved.

An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for Wireless Sensor Networks

Science.gov (United States)

Abba, Sani; Lee, Jeong-A

2015-01-01

We propose an autonomous self-aware and adaptive fault-tolerant routing technique (ASAART) for wireless sensor networks. We address the limitations of self-healing routing (SHR) and self-selective routing (SSR) techniques for routing sensor data. We also examine the integration of autonomic self-aware and adaptive fault detection and resiliency techniques for route formation and route repair to provide resilience to errors and failures. We achieved this by using a combined continuous and slotted prioritized transmission back-off delay to obtain local and global network state information, as well as multiple random functions for attaining faster routing convergence and reliable route repair despite transient and permanent node failure rates and efficient adaptation to instantaneous network topology changes. The results of simulations based on a comparison of the ASAART with the SHR and SSR protocols for five different simulated scenarios in the presence of transient and permanent node failure rates exhibit a greater resiliency to errors and failure and better routing performance in terms of the number of successfully delivered network packets, end-to-end delay, delivered MAC layer packets, packet error rate, as well as efficient energy conservation in a highly congested, faulty, and scalable sensor network. PMID:26295236

From molecular genetics to phylodynamics: evolutionary relevance of mutation rates across viruses.

Directory of Open Access Journals (Sweden)

Rafael Sanjuán

Full Text Available Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies.

Physiological Self-Regulation and Adaptive Automation

Science.gov (United States)

Prinzell, Lawrence J.; Pope, Alan T.; Freeman, Frederick G.

2007-01-01

Adaptive automation has been proposed as a solution to current problems of human-automation interaction. Past research has shown the potential of this advanced form of automation to enhance pilot engagement and lower cognitive workload. However, there have been concerns voiced regarding issues, such as automation surprises, associated with the use of adaptive automation. This study examined the use of psychophysiological self-regulation training with adaptive automation that may help pilots deal with these problems through the enhancement of cognitive resource management skills. Eighteen participants were assigned to 3 groups (self-regulation training, false feedback, and control) and performed resource management, monitoring, and tracking tasks from the Multiple Attribute Task Battery. The tracking task was cycled between 3 levels of task difficulty (automatic, adaptive aiding, manual) on the basis of the electroencephalogram-derived engagement index. The other two tasks remained in automatic mode that had a single automation failure. Those participants who had received self-regulation training performed significantly better and reported lower National Aeronautics and Space Administration Task Load Index scores than participants in the false feedback and control groups. The theoretical and practical implications of these results for adaptive automation are discussed.

Rate Adaptive OFDMA Communication Systems

International Nuclear Information System (INIS)

Abdelhakim, M.M.M.

2009-01-01

Due to the varying nature of the wireless channels, adapting the transmission parameters, such as code rate, modulation order and power, in response to the channel variations provides a significant improvement in the system performance. In the OFDM systems, Per-Frame adaptation (PFA) can be employed where the transmission variables are fixed over a given frame and may change from one frame to the other. Subband (tile) loading offers more degrees of adaptation such that each group of carriers (subband) uses the same transmission parameters and different subbands may use different parameters. Changing the code rate for each tile in the same frame, results in transmitting multiple codewords (MCWs) for a single frame. In this thesis a scheme is proposed for adaptively changing the code rate of coded OFDMA systems via changing the puncturing rate within a single codeword (SCW). In the proposed structure, the data is encoded with the lowest available code rate then it is divided among the different tiles where it is punctured adaptively based on some measure of the channel quality for each tile. The proposed scheme is compared against using multiple codewords (MCWs) where the different code rates for the tiles are obtained using separate encoding processes. For bit interleaved coded modulation architecture two novel interleaving methods are proposed, namely the puncturing dependant interleaver (PDI) and interleaved puncturing (IntP), which provide larger interleaving depth. In the PDI method the coded bits with the same rate over different tiles are grouped for interleaving. In IntP structure the interleaving is performed prior to puncturing. The performance of the adaptive puncturing technique is investigated under constant bit rate constraint and variable bit rate. Two different adaptive modulation and coding (AMC) selection methods are examined for variable bit rate adaptive system. The first is a recursive scheme that operates directly on the SNR whereas the second

A self-driven temperature and flow rate co-adjustment mechanism based on Shape-Memory-Alloy (SMA) assembly for an adaptive thermal control coldplate module with on-orbit service characteristics

International Nuclear Information System (INIS)

Guo, Wei; Li, Yunhua; Li, Yun-Ze; Zhong, Ming-Liang; Wang, Sheng-Nan; Wang, Ji-Xiang; Zhang, Jia-Xun

2017-01-01

Highlights: • A self-driven temperature and flow rate co-adjustment mechanism based on SMA assembly is proposed. • An adaptive thermal control coldplate module (TCCM) is introduced. • A testbed is set up to investigate the TCCM adaptive thermal management performances. • The TCCM has the potential for spacecrafts on-orbit services. - Abstract: An adaptive thermal control coldplate module (TCCM) was proposed in this paper to fulfill the requirements of modular thermal control systems for spacecrafts on-orbit services. The TCCM could provide flow rate and temperature co-adjustment by using Shape-Memory-Alloy (SMA) assembly which possesses self-driven abilities. In this paper, the adaptive thermal management mechanism of the TCCM integrated with a single phase mechanically pumped fluid loop (SPMPFL) is described in detail, a verification testbed was established to examine the TCCM dynamic characteristics. Various working conditions such as inlet temperature, flow rate and thermal load disturbances were imposed on the TCCM to inspect its startup and transient performance. It was observed that the TCCM may present robust temperature control results with low overshoot (maximum 16.8%) and small temperature control error (minimum 0.18%), fast time response (minimum 600 s) was also revealed. The results demonstrated that the well-designed TCCM provided effective autonomous flow-rate and temperature co-adjustment operations, which may be a promising candidate for realizing modular level adaptive thermal management for spacecrafts on-orbit services.

Asymptotics of steady states of a selection–mutation equation for small mutation rate

KAUST Repository

Calsina, Àngel

2013-12-01

We consider a selection-mutation equation for the density of individuals with respect to a continuous phenotypic evolutionary trait. We assume that the competition term for an individual with a given trait depends on the traits of all the other individuals, therefore giving an infinite-dimensional nonlinearity. Mutations are modelled by means of an integral operator. We prove existence of steady states and show that, when the mutation rate goes to zero, the asymptotic profile of the population is a Cauchy distribution. © Royal Society of Edinburgh 2013.

Asymptotics of steady states of a selection–mutation equation for small mutation rate

KAUST Repository

Calsina, À ngel; Cuadrado, Sí lvia; Desvillettes, Laurent; Raoul, Gaë l

2013-01-01

We consider a selection-mutation equation for the density of individuals with respect to a continuous phenotypic evolutionary trait. We assume that the competition term for an individual with a given trait depends on the traits of all the other individuals, therefore giving an infinite-dimensional nonlinearity. Mutations are modelled by means of an integral operator. We prove existence of steady states and show that, when the mutation rate goes to zero, the asymptotic profile of the population is a Cauchy distribution. © Royal Society of Edinburgh 2013.

An alternative derivation of the stationary distribution of the multivariate neutral Wright-Fisher model for low mutation rates with a view to mutation rate estimation from site frequency data.

Science.gov (United States)

Schrempf, Dominik; Hobolth, Asger

2017-04-01

Recently, Burden and Tang (2016) provided an analytical expression for the stationary distribution of the multivariate neutral Wright-Fisher model with low mutation rates. In this paper we present a simple, alternative derivation that illustrates the approximation. Our proof is based on the discrete multivariate boundary mutation model which has three key ingredients. First, the decoupled Moran model is used to describe genetic drift. Second, low mutation rates are assumed by limiting mutations to monomorphic states. Third, the mutation rate matrix is separated into a time-reversible part and a flux part, as suggested by Burden and Tang (2016). An application of our result to data from several great apes reveals that the assumption of stationarity may be inadequate or that other evolutionary forces like selection or biased gene conversion are acting. Furthermore we find that the model with a reversible mutation rate matrix provides a reasonably good fit to the data compared to the one with a non-reversible mutation rate matrix. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The application of a linear algebra to the analysis of mutation rates.

Science.gov (United States)

Jones, M E; Thomas, S M; Clarke, K

1999-07-07

Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected. Copyright 1999 Academic Press.

Closed-loop adaptation of neurofeedback based on mental effort facilitates reinforcement learning of brain self-regulation.

Science.gov (United States)

Bauer, Robert; Fels, Meike; Royter, Vladislav; Raco, Valerio; Gharabaghi, Alireza

2016-09-01

Considering self-rated mental effort during neurofeedback may improve training of brain self-regulation. Twenty-one healthy, right-handed subjects performed kinesthetic motor imagery of opening their left hand, while threshold-based classification of beta-band desynchronization resulted in proprioceptive robotic feedback. The experiment consisted of two blocks in a cross-over design. The participants rated their perceived mental effort nine times per block. In the adaptive block, the threshold was adjusted on the basis of these ratings whereas adjustments were carried out at random in the other block. Electroencephalography was used to examine the cortical activation patterns during the training sessions. The perceived mental effort was correlated with the difficulty threshold of neurofeedback training. Adaptive threshold-setting reduced mental effort and increased the classification accuracy and positive predictive value. This was paralleled by an inter-hemispheric cortical activation pattern in low frequency bands connecting the right frontal and left parietal areas. Optimal balance of mental effort was achieved at thresholds significantly higher than maximum classification accuracy. Rating of mental effort is a feasible approach for effective threshold-adaptation during neurofeedback training. Closed-loop adaptation of the neurofeedback difficulty level facilitates reinforcement learning of brain self-regulation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Gamma radiation-induced heritable mutations at repetitive DNA loci in out-bred mice

International Nuclear Information System (INIS)

Somers, C.M.; Sharma, R.; Quinn, J.S.; Boreham, D.R.

2004-01-01

Recent studies have shown that expanded-simple-tandem-repeat (ESTR) DNA loci are efficient genetic markers for detecting radiation-induced germ line mutations in mice. Dose responses following irradiation, however, have only been characterized in a small number of inbred mouse strains, and no studies have applied Esters to examine potential modifiers of radiation risk, such as adaptive response. We gamma-irradiated groups of male out-bred Swiss-Webster mice with single acute doses of 0.5 and 1.0 Gy, and compared germ line mutation rates at ESTR loci to a sham-irradiated control. To test for evidence of adaptive response we treated a third group with a total dose of 1.1 Gy that was fractionated into a 0.1 Gy adapting dose, followed by a challenge dose of 1.0 Gy 24 h later. Paternal mutation rates were significantly elevated above the control in the 0.5 Gy (2.8-fold) and 1.0 Gy (3.0-fold) groups, but were similar to each other despite the difference in radiation dose. The doubling dose for paternal mutation induction was 0.26 Gy (95% CI = 0.14-0.51 Gy). Males adapted with a 0.1 Gy dose prior to a 1.0 Gy challenge dose had mutation rates that were not significantly elevated above the control, and were 43% reduced compared to those receiving single doses. We conclude that pre-meiotic male germ cells in out-bred Swiss-Webster mice are sensitive to ESTR mutations induced by acute doses of ionizing radiation, but mutation induction may become saturated at a lower dose than in some strains of inbred mice. Reduced mutation rates in the adapted group provide intriguing evidence for suppression of ESTR mutations in the male germline through adaptive response. Repetitive DNA markers may be useful tools for exploration of biological factors affecting the probability of heritable mutations caused by low-dose ionizing radiation exposure. The biological significance of ESTR mutations in terms of radiation risk assessment, however, is still undetermined

Mitochondrial Mutation Rate, Spectrum and Heteroplasmy in Caenorhabditis elegans Spontaneous Mutation Accumulation Lines of Differing Population Size.

Science.gov (United States)

Konrad, Anke; Thompson, Owen; Waterston, Robert H; Moerman, Donald G; Keightley, Peter D; Bergthorsson, Ulfar; Katju, Vaishali

2017-06-01

Mitochondrial genomes of metazoans, given their elevated rates of evolution, have served as pivotal markers for phylogeographic studies and recent phylogenetic events. In order to determine the dynamics of spontaneous mitochondrial mutations in small populations in the absence and presence of selection, we evolved mutation accumulation (MA) lines of Caenorhabditis elegans in parallel over 409 consecutive generations at three varying population sizes of N = 1, 10, and 100 hermaphrodites. The N =1 populations should have a minimal influence of natural selection to provide the spontaneous mutation rate and the expected rate of neutral evolution, whereas larger population sizes should experience increasing intensity of selection. New mutations were identified by Illumina paired-end sequencing of 86 mtDNA genomes across 35 experimental lines and compared with published genomes of natural isolates. The spontaneous mitochondrial mutation rate was estimated at 1.05 × 10-7/site/generation. A strong G/C→A/T mutational bias was observed in both the MA lines and the natural isolates. This suggests that the low G + C content at synonymous sites is the product of mutation bias rather than selection as previously proposed. The mitochondrial effective population size per worm generation was estimated to be 62. Although it was previously concluded that heteroplasmy was rare in C. elegans, the vast majority of mutations in this study were heteroplasmic despite an experimental regime exceeding 400 generations. The frequencies of frameshift and nonsynonymous mutations were negatively correlated with population size, which suggests their deleterious effects on fitness and a potent role for selection in their eradication. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mutator suppression and escape from replication error-induced extinction in yeast.

Directory of Open Access Journals (Sweden)

Alan J Herr

2011-10-01

Full Text Available Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10⁻³ inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer.

Genome Mutational and Transcriptional Hotspots Are Traps for Duplicated Genes and Sources of Adaptations.

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Fares, Mario A; Sabater-Muñoz, Beatriz; Toft, Christina

2017-05-01

Gene duplication generates new genetic material, which has been shown to lead to major innovations in unicellular and multicellular organisms. A whole-genome duplication occurred in the ancestor of Saccharomyces yeast species but 92% of duplicates returned to single-copy genes shortly after duplication. The persisting duplicated genes in Saccharomyces led to the origin of major metabolic innovations, which have been the source of the unique biotechnological capabilities in the Baker's yeast Saccharomyces cerevisiae. What factors have determined the fate of duplicated genes remains unknown. Here, we report the first demonstration that the local genome mutation and transcription rates determine the fate of duplicates. We show, for the first time, a preferential location of duplicated genes in the mutational and transcriptional hotspots of S. cerevisiae genome. The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates. Genome mutational and transcriptional hotspots are rich in duplicates with large repetitive promoter elements. Saccharomyces cerevisiae shows more tolerance to deleterious mutations in duplicates with repetitive promoter elements, which in turn exhibit higher transcriptional plasticity against environmental perturbations. Our data demonstrate that the genome traps duplicates through the accelerated regulatory and functional divergence of their gene copies providing a source of novel adaptations in yeast. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Mutation rate estimation for 15 autosomal STR loci in a large population from Mainland China.

Science.gov (United States)

Zhao, Zhuo; Zhang, Jie; Wang, Hua; Liu, Zhi-Peng; Liu, Ming; Zhang, Yuan; Sun, Li; Zhang, Hui

2015-09-01

STR, short tandem repeats, are well known as a type of powerful genetic marker and widely used in studying human population genetics. Compared with the conventional genetic markers, the mutation rate of STR is higher. Additionally, the mutations of STR loci do not lead to genetic inconsistencies between the genotypes of parents and children; therefore, the analysis of STR mutation is more suited to assess the population mutation. In this study, we focused on 15 autosomal STR loci. DNA samples from a total of 42,416 unrelated healthy individuals (19,037 trios) from the population of Mainland China collected between Jan 2012 and May 2014 were successfully investigated. In our study, the allele frequencies, paternal mutation rates, maternal mutation rates and average mutation rates were detected. Furthermore, we also investigated the relationship between paternal ages, maternal ages, area, the time of pregnancy and average mutation rate. We found that the paternal mutation rate was higher than the maternal mutation rate and the paternal, maternal, and average mutation rates had a positive correlation with paternal age, maternal age and the time of pregnancy respectively. Additionally, the average mutation rate of coastal areas was higher than that of inland areas.

Hybridization alters spontaneous mutation rates in a parent-of-origin-dependent fashion in Arabidopsis.

Science.gov (United States)

Bashir, Tufail; Sailer, Christian; Gerber, Florian; Loganathan, Nitin; Bhoopalan, Hemadev; Eichenberger, Christof; Grossniklaus, Ueli; Baskar, Ramamurthy

2014-05-01

Over 70 years ago, increased spontaneous mutation rates were observed in Drosophila spp. hybrids, but the genetic basis of this phenomenon is not well understood. The model plant Arabidopsis (Arabidopsis thaliana) offers unique opportunities to study the types of mutations induced upon hybridization and the frequency of their occurrence. Understanding the mutational effects of hybridization is important, as many crop plants are grown as hybrids. Besides, hybridization is important for speciation and its effects on genome integrity could be critical, as chromosomal rearrangements can lead to reproductive isolation. We examined the rates of hybridization-induced point and frameshift mutations as well as homologous recombination events in intraspecific Arabidopsis hybrids using a set of transgenic mutation detector lines that carry mutated or truncated versions of a reporter gene. We found that hybridization alters the frequency of different kinds of mutations. In general, Columbia (Col)×Cape Verde Islands and Col×C24 hybrid progeny had decreased T→G and T→A transversion rates but an increased C→T transition rate. Significant changes in frameshift mutation rates were also observed in some hybrids. In Col×C24 hybrids, there is a trend for increased homologous recombination rates, except for the hybrids from one line, while in Col×Cape Verde Islands hybrids, this rate is decreased. The overall genetic distance of the parents had no influence on mutation rates in the progeny, as closely related accessions on occasion displayed higher mutation rates than accessions that are separated farther apart. However, reciprocal hybrids had significantly different mutation rates, suggesting parent-of-origin-dependent effects on the mutation frequency.

Impact of Self-Interference on the Performance of Joint Partial RAKE Receiver and Adaptive Modulation

KAUST Repository

Nam, Sung Sik

2016-11-23

In this paper, we investigate the impact of self-interference on the performance of a joint partial RAKE (PRAKE) receiver and adaptive modulation over both independent and identically distributed and independent but non-identically distributed Rayleigh fading channels. To better observe the impact of self-interference, our approach starts from considering the signal to interference plus noise ratio. Specifically, we accurately analyze the outage probability, the average spectral efficiency, and the average bit error rate as performance measures in the presence of self-interference. Several numerical and simulation results are selected to present the performance of the joint PRAKE receiver and adaptive modulation subject to self-interference.

Molecular evolution and thermal adaptation

Science.gov (United States)

Chen, Peiqiu

2011-12-01

In this thesis, we address problems in molecular evolution, thermal adaptation, and the kinetics of adaptation of bacteria and viruses to elevated environmental temperatures. We use a nearly neutral fitness model where the replication speed of an organism is proportional to the copy number of folded proteins. Our model reproduces the distribution of stabilities of natural proteins in excellent agreement with experiment. We find that species with high mutation rates tend to have less stable proteins compared to species with low mutation rate. We found that a broad distribution of protein stabilities observed in the model and in experiment is the key determinant of thermal response for viruses and bacteria. Our results explain most of the earlier experimental observations: striking asymmetry of thermal response curves, the absence of evolutionary trade-off which was expected but not found in experiments, correlation between denaturation temperature for several protein families and the Optimal Growth Temperature (OGT) of their carrier organisms, and proximity of bacterial or viral OGTs to their evolutionary temperatures. Our theory quantitatively and with high accuracy described thermal response curves for 35 bacterial species. The model also addresses the key to adaptation is in weak-link genes (WLG), which encode least thermodynamically stable essential proteins in the proteome. We observe, as in experiment, a two-stage adaptation process. The first stage is a Luria-Delbruck type of selection, whereby rare WLG alleles, whose proteins are more stable than WLG proteins of the majority of the population (either due to standing genetic variation or due to an early acquired mutation), rapidly rise to fixation. The second stage constitutes subsequent slow accumulation of mutations in an adapted population. As adaptation progresses, selection regime changes from positive to neutral: Selection coefficient of beneficial mutations scales as a negative power of number of

Some improvements on adaptive genetic algorithms for reliability-related applications

Energy Technology Data Exchange (ETDEWEB)

Ye Zhisheng, E-mail: yez@nus.edu.s [Department of Industrial and Systems Engineering, National University of Singapore, Singapore 119 260 (Singapore); Li Zhizhong [Department of Industrial Engineering, Tsinghua University, beijing 100084 (China); Xie Min [Department of Industrial and Systems Engineering, National University of Singapore, Singapore 119 260 (Singapore)

2010-02-15

Adaptive genetic algorithms (GAs) have been shown to be able to improve GA performance in reliability-related optimization studies. However, there are different ways to implement adaptive GAs, some of which are even in conflict with each other. In this study, a simple parameter-adjusting method using mean and variance of each generation is introduced. This method is used to compare two of such conflicting adaptive GA methods: GAs with increasing mutation rate and decreasing crossover rate and GAs with decreasing mutation rate and increasing crossover rate. The illustrative examples indicate that adaptive GAs with decreasing mutation rate and increasing crossover rate finally yield better results. Furthermore, a population disturbance method is proposed to avoid local optimum solutions. This idea is similar to exotic migration to a tribal society. To solve the problem of large solution space, a variable roughening method is also embedded into GA. Two case studies are presented to demonstrate the effectiveness of the proposed method.

Some improvements on adaptive genetic algorithms for reliability-related applications

International Nuclear Information System (INIS)

Ye Zhisheng; Li Zhizhong; Xie Min

2010-01-01

Adaptive genetic algorithms (GAs) have been shown to be able to improve GA performance in reliability-related optimization studies. However, there are different ways to implement adaptive GAs, some of which are even in conflict with each other. In this study, a simple parameter-adjusting method using mean and variance of each generation is introduced. This method is used to compare two of such conflicting adaptive GA methods: GAs with increasing mutation rate and decreasing crossover rate and GAs with decreasing mutation rate and increasing crossover rate. The illustrative examples indicate that adaptive GAs with decreasing mutation rate and increasing crossover rate finally yield better results. Furthermore, a population disturbance method is proposed to avoid local optimum solutions. This idea is similar to exotic migration to a tribal society. To solve the problem of large solution space, a variable roughening method is also embedded into GA. Two case studies are presented to demonstrate the effectiveness of the proposed method.

Germline mutation rates at tandem repeat loci in DNA-repair deficient mice

International Nuclear Information System (INIS)

Barber, Ruth C.; Miccoli, Laurent; Buul, Paul P.W. van; Burr, Karen L.-A.; Duyn-Goedhart, Annemarie van; Angulo, Jaime F.; Dubrova, Yuri E.

2004-01-01

Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of non-exposed and irradiated severe combined immunodeficient (scid) and poly(ADP-ribose) polymerase (PARP-1 -/- ) deficient male mice. Non-exposed scid and PARP -/- male mice showed considerably elevated ESTR mutation rates, far higher than those in wild-type isogenic mice and other inbred strains. The irradiated scid and PARP-1 -/- male mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated wild-type isogenic males. ESTR mutation spectra in the scid and PARP-1 -/- strains did not differ from those in the isogenic wild-type strains. Considering these data and the results of previous studies, we propose that a delay in repair of DNA damage in scid and PARP-1 -/- mice could result in replication fork pausing which, in turn, may affect ESTR mutation rate in the non-irradiated males. The lack of mutation induction in irradiated scid and PARP-1 -/- can be explained by the high cell killing effects of irradiation on the germline of deficient mice

Optimal mutation rates for the (1+λ) EA on OneMax

DEFF Research Database (Denmark)

Gießen, Christian; Witt, Carsten

2016-01-01

We study the (1 + λ) EA with mutation probability c/n, where c > 0 is a constant, on the ONEMAX problem. Using an improved variable drift theorem, we show that upper and lower bounds on the expected runtime of the (1+λ) EA obtained from variable drift theorems are at most apart by a small lower...... mutation rates for the (1+λ) EA for various parameter settings of c and λ and also for moderate sizes of n. This makes the need for potentially lengthy and costly experiments in order to optimize the parameters unnecessary. Interestingly, even for moderate n and not too small λ it turns out that mutation...... rates up to 10% larger than the asymptotically optimal rate 1/n minimize the expected runtime. However, in absolute terms the expected runtime does not change by much when replacing 1/n with the optimal mutation rate....

Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.

Science.gov (United States)

Chung, Aeri; Jin, Bora; Han, Kwang-Hyub; Ahn, Sang Hoon; Kim, Seungtaek

2017-01-01

Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Experimental investigation of biomimetic self-pumping and self-adaptive transpiration cooling.

Science.gov (United States)

Jiang, Pei-Xue; Huang, Gan; Zhu, Yinhai; Xu, Ruina; Liao, Zhiyuan; Lu, Taojie

2017-09-01

Transpiration cooling is an effective way to protect high heat flux walls. However, the pumps for the transpiration cooling system make the system more complex and increase the load, which is a huge challenge for practical applications. A biomimetic self-pumping transpiration cooling system was developed inspired by the process of trees transpiration that has no pumps. An experimental investigation showed that the water coolant automatically flowed from the water tank to the hot surface with a height difference of 80 mm without any pumps. A self-adaptive transpiration cooling system was then developed based on this mechanism. The system effectively cooled the hot surface with the surface temperature kept to about 373 K when the heating flame temperature was 1639 K and the heat flux was about 0.42 MW m -2 . The cooling efficiency reached 94.5%. The coolant mass flow rate adaptively increased with increasing flame heat flux from 0.24 MW m -2 to 0.42 MW m -2 while the cooled surface temperature stayed around 373 K. Schlieren pictures showed a protective steam layer on the hot surface which blocked the flame heat flux to the hot surface. The protective steam layer thickness also increased with increasing heat flux.

[Stress-induced cellular adaptive mutagenesis].

Science.gov (United States)

Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

Properties of a genetic algorithm extended by a random self-learning operator and asymmetric mutations: A convergence study for a task of powder-pattern indexing

International Nuclear Information System (INIS)

Paszkowicz, Wojciech

2006-01-01

Genetic algorithms represent a powerful global-optimisation tool applicable in solving tasks of high complexity in science, technology, medicine, communication, etc. The usual genetic-algorithm calculation scheme is extended here by introduction of a quadratic self-learning operator, which performs a partial local search for randomly selected representatives of the population. This operator is aimed as a minor deterministic contribution to the (stochastic) genetic search. The population representing the trial solutions is split into two equal subpopulations allowed to exhibit different mutation rates (so called asymmetric mutation). The convergence is studied in detail exploiting a crystallographic-test example of indexing of powder diffraction data of orthorhombic lithium copper oxide, varying such parameters as mutation rates and the learning rate. It is shown through the averaged (over the subpopulation) fitness behaviour, how the genetic diversity in the population depends on the mutation rate of the given subpopulation. Conditions and algorithm parameter values favourable for convergence in the framework of proposed approach are discussed using the results for the mentioned example. Further data are studied with a somewhat modified algorithm using periodically varying mutation rates and a problem-specific operator. The chance of finding the global optimum and the convergence speed are observed to be strongly influenced by the effective mutation level and on the self-learning level. The optimal values of these two parameters are about 6 and 5%, respectively. The periodic changes of mutation rate are found to improve the explorative abilities of the algorithm. The results of the study confirm that the applied methodology leads to improvement of the classical genetic algorithm and, therefore, it is expected to be helpful in constructing of algorithms permitting to solve similar tasks of higher complexity

Mutation and evolutionary rates in adélie penguins from the antarctic.

Directory of Open Access Journals (Sweden)

Craig D Millar

2008-10-01

Full Text Available Precise estimations of molecular rates are fundamental to our understanding of the processes of evolution. In principle, mutation and evolutionary rates for neutral regions of the same species are expected to be equal. However, a number of recent studies have shown that mutation rates estimated from pedigree material are much faster than evolutionary rates measured over longer time periods. To resolve this apparent contradiction, we have examined the hypervariable region (HVR I of the mitochondrial genome using families of Adélie penguins (Pygoscelis adeliae from the Antarctic. We sequenced 344 bps of the HVR I from penguins comprising 508 families with 915 chicks, together with both their parents. All of the 62 germline heteroplasmies that we detected in mothers were also detected in their offspring, consistent with maternal inheritance. These data give an estimated mutation rate (micro of 0.55 mutations/site/Myrs (HPD 95% confidence interval of 0.29-0.88 mutations/site/Myrs after accounting for the persistence of these heteroplasmies and the sensitivity of current detection methods. In comparison, the rate of evolution (k of the same HVR I region, determined using DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period, was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17. Importantly, the latter rate is not statistically different from our estimate of the mutation rate. These results are in contrast to the view that molecular rates are time dependent.

Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated Learning

Science.gov (United States)

2015-03-01

ARL-SR-0318 ● MAR 2015 US Army Research Laboratory Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated...Adaptive Intelligent Tutoring Systems for Self-Regulated Learning by Robert A Sottilare Human Research and Engineering Directorate, ARL...TITLE AND SUBTITLE Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated Learning 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

The sequence spectrum of frameshift reversions obtained with a novel adaptive mutation assay in Saccharomyces cerevisiae

Directory of Open Access Journals (Sweden)

Erich Heidenreich

2016-12-01

Full Text Available Research on the mechanisms of adaptive mutagenesis in resting, i.e. non-replicating cells relies on appropriate mutation assays. Here we provide a novel procedure for the detection of frameshift-reverting mutations in yeast. Proliferation of non-reverted cells in this assay is suppressed by the lack of a fermentable carbon source. The test allele was constructed in a way that the reversions mimic microsatellite instability, a condition often found in cancer cells. We show the cell numbers during these starvation conditions and provide a DNA sequence spectrum of a representative set of revertants. The data in this article support the publication "Glucose starvation as a selective tool for the study of adaptive mutations in Saccharomyces cerevisiae" (Heidenreich and Steinboeck, 2016 [1].

High mitochondrial mutation rates estimated from deep-rooting Costa Rican pedigrees

Science.gov (United States)

Madrigal, Lorena; Melendez-Obando, Mauricio; Villegas-Palma, Ramon; Barrantes, Ramiro; Raventos, Henrieta; Pereira, Reynaldo; Luiselli, Donata; Pettener, Davide; Barbujani, Guido

2012-01-01

Estimates of mutation rates for the noncoding hypervariable Region I (HVR-I) of mitochondrial DNA (mtDNA) vary widely, depending on whether they are inferred from phylogenies (assuming that molecular evolution is clock-like) or directly from pedigrees. All pedigree-based studies so far were conducted on populations of European origin. In this paper we analyzed 19 deep-rooting pedigrees in a population of mixed origin in Costa Rica. We calculated two estimates of the HVR-I mutation rate, one considering all apparent mutations, and one disregarding changes at sites known to be mutational hot spots and eliminating genealogy branches which might be suspected to include errors, or unrecognized adoptions along the female lines. At the end of this procedure, we still observed a mutation rate equal to 1.24 × 10−6, per site per year, i.e., at least three-fold as high as estimates derived from phylogenies. Our results confirm that mutation rates observed in pedigrees are much higher than estimated assuming a neutral model of long-term HVRI evolution. We argue that, until the cause of these discrepancies will be fully understood, both lower estimates (i.e., those derived from phylogenetic comparisons) and higher, direct estimates such as those obtained in this study, should be considered when modeling evolutionary and demographic processes. PMID:22460349

Rates of Mutation and Host Transmission for an Escherichia coli Clone over 3 Years

Science.gov (United States)

Reeves, Peter R.; Liu, Bin; Zhou, Zhemin; Li, Dan; Guo, Dan; Ren, Yan; Clabots, Connie; Lan, Ruiting; Johnson, James R.; Wang, Lei

2011-01-01

Although over 50 complete Escherichia coli/Shigella genome sequences are available, it is only for closely related strains, for example the O55:H7 and O157:H7 clones of E. coli, that we can assign differences to individual evolutionary events along specific lineages. Here we sequence the genomes of 14 isolates of a uropathogenic E. coli clone that persisted for 3 years within a household, including a dog, causing a urinary tract infection (UTI) in the dog after 2 years. The 20 mutations observed fit a single tree that allows us to estimate the mutation rate to be about 1.1 per genome per year, with minimal evidence for adaptive change, including in relation to the UTI episode. The host data also imply at least 6 host transfer events over the 3 years, with 2 lineages present over much of that period. To our knowledge, these are the first direct measurements for a clone in a well-defined host community that includes rates of mutation and host transmission. There is a concentration of non-synonymous mutations associated with 2 transfers to the dog, suggesting some selection pressure from the change of host. However, there are no changes to which we can attribute the UTI event in the dog, which suggests that this occurrence after 2 years of the clone being in the household may have been due to chance, or some unknown change in the host or environment. The ability of a UTI strain to persist for 2 years and also to transfer readily within a household has implications for epidemiology, diagnosis, and clinical intervention. PMID:22046404

How Large Asexual Populations Adapt

Science.gov (United States)

Desai, Michael

2007-03-01

We often think of beneficial mutations as being rare, and of adaptation as a sequence of selected substitutions: a beneficial mutation occurs, spreads through a population in a selective sweep, then later another beneficial mutation occurs, and so on. This simple picture is the basis for much of our intuition about adaptive evolution, and underlies a number of practical techniques for analyzing sequence data. Yet many large and mostly asexual populations -- including a wide variety of unicellular organisms and viruses -- live in a very different world. In these populations, beneficial mutations are common, and frequently interfere or cooperate with one another as they all attempt to sweep simultaneously. This radically changes the way these populations adapt: rather than an orderly sequence of selective sweeps, evolution is a constant swarm of competing and interfering mutations. I will describe some aspects of these dynamics, including why large asexual populations cannot evolve very quickly and the character of the diversity they maintain. I will explain how this changes our expectations of sequence data, how sex can help a population adapt, and the potential role of ``mutator'' phenotypes with abnormally high mutation rates. Finally, I will discuss comparisons of these predictions with evolution experiments in laboratory yeast populations.

A hydraulic hybrid propulsion method for automobiles with self-adaptive system

International Nuclear Information System (INIS)

Wu, Wei; Hu, Jibin; Yuan, Shihua; Di, Chongfeng

2016-01-01

A hydraulic hybrid vehicle with the self-adaptive system is proposed. The mode-switching between the driving mode and the hydraulic regenerative braking mode is realised by the pressure cross-feedback control. Extensive simulated and tested results are presented. The control parameters are reduced and the energy efficiency can be increased by the self-adaptive system. The mode-switching response is fast. The response time can be adjusted by changing the controlling spool diameter of the hydraulic operated check valve in the self-adaptive system. The closing of the valve becomes faster with a smaller controlling spool diameter. The hydraulic regenerative braking mode can be achieved by changing the hydraulic transformer controlled angle. Compared with the convention electric-hydraulic system, the self-adaptive system for the hydraulic hybrid vehicle mode-switching has a higher reliability and a lower cost. The efficiency of the hydraulic regenerative braking is also increased. - Highlights: • A new hybrid system with a self-adaptive system for automobiles is presented. • The mode-switching is realised by the pressure cross-feedback control. • The energy efficiency can be increased with the self-adaptive system. • The control parameters are reduced with the self-adaptive system.

Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

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Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

2004-11-22

There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

Non-homologous end joining dependency of γ-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

International Nuclear Information System (INIS)

Heidenreich, Erich; Eisler, Herfried

2004-01-01

There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by γ-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the γ-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development

MutS and MutL are dispensable for maintenance of the genomic mutation rate in the halophilic archaeon Halobacterium salinarum NRC-1.

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Courtney R Busch

Full Text Available BACKGROUND: The genome of the halophilic archaeon Halobacterium salinarum NRC-1 encodes for homologs of MutS and MutL, which are key proteins of a DNA mismatch repair pathway conserved in Bacteria and Eukarya. Mismatch repair is essential for retaining the fidelity of genetic information and defects in this pathway result in the deleterious accumulation of mutations and in hereditary diseases in humans. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the spontaneous genomic mutation rate of H. salinarum NRC-1 using fluctuation tests targeting genes of the uracil monophosphate biosynthesis pathway. We found that H. salinarum NRC-1 has a low incidence of mutation suggesting the presence of active mechanisms to control spontaneous mutations during replication. The spectrum of mutational changes found in H. salinarum NRC-1, and in other archaea, appears to be unique to this domain of life and might be a consequence of their adaption to extreme environmental conditions. In-frame targeted gene deletions of H. salinarum NRC-1 mismatch repair genes and phenotypic characterization of the mutants demonstrated that the mutS and mutL genes are not required for maintenance of the observed mutation rate. CONCLUSIONS/SIGNIFICANCE: We established that H. salinarum NRC-1 mutS and mutL genes are redundant to an alternative system that limits spontaneous mutation in this organism. This finding leads to the puzzling question of what mechanism is responsible for maintenance of the low genomic mutation rates observed in the Archaea, which for the most part do not have MutS and MutL homologs.

Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution

DEFF Research Database (Denmark)

Utrilla, José; O'Brien, Edward J.; Chen, Ke

2016-01-01

Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear se...

The allele-frequency spectrum in a decoupled Moran model with mutation, drift, and directional selection, assuming small mutation rates.

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Vogl, Claus; Clemente, Florian

2012-05-01

We analyze a decoupled Moran model with haploid population size N, a biallelic locus under mutation and drift with scaled forward and backward mutation rates θ(1)=μ(1)N and θ(0)=μ(0)N, and directional selection with scaled strength γ=sN. With small scaled mutation rates θ(0) and θ(1), which is appropriate for single nucleotide polymorphism data in highly recombining regions, we derive a simple approximate equilibrium distribution for polymorphic alleles with a constant of proportionality. We also put forth an even simpler model, where all mutations originate from monomorphic states. Using this model we derive the sojourn times, conditional on the ancestral and fixed allele, and under equilibrium the distributions of fixed and polymorphic alleles and fixation rates. Furthermore, we also derive the distribution of small samples in the diffusion limit and provide convenient recurrence relations for calculating this distribution. This enables us to give formulas analogous to the Ewens-Watterson estimator of θ for biased mutation rates and selection. We apply this theory to a polymorphism dataset of fourfold degenerate sites in Drosophila melanogaster. Copyright © 2012 Elsevier Inc. All rights reserved.

Self-adaptive strain-relaxation optimization for high-energy lithium storage material through crumpling of graphene.

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Zhao, Yunlong; Feng, Jiangang; Liu, Xue; Wang, Fengchao; Wang, Lifen; Shi, Changwei; Huang, Lei; Feng, Xi; Chen, Xiyuan; Xu, Lin; Yan, Mengyu; Zhang, Qingjie; Bai, Xuedong; Wu, Hengan; Mai, Liqiang

2014-08-01

High-energy lithium battery materials based on conversion/alloying reactions have tremendous potential applications in new generation energy storage devices. However, these applications are limited by inherent large volume variations and sluggish kinetics. Here we report a self-adaptive strain-relaxed electrode through crumpling of graphene to serve as high-stretchy protective shells on metal framework, to overcome these limitations. The graphene sheets are self-assembled and deeply crumpled into pinecone-like structure through a contraction-strain-driven crumpling method. The as-prepared electrode exhibits high specific capacity (2,165 mAh g(-1)), fast charge-discharge rate (20 A g(-1)) with no capacity fading in 1,000 cycles. This kind of crumpled graphene has self-adaptive behaviour of spontaneous unfolding-folding synchronized with cyclic expansion-contraction volumetric variation of core materials, which can release strain and maintain good electric contact simultaneously. It is expected that such findings will facilitate the applications of crumpled graphene and the self-adaptive materials.

From a distance: implications of spontaneous self-distancing for adaptive self-reflection.

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Ayduk, Ozlem; Kross, Ethan

2010-05-01

Although recent experimental work indicates that self-distancing facilitates adaptive self-reflection, it remains unclear (a) whether spontaneous self-distancing leads to similar adaptive outcomes, (b) how spontaneous self-distancing relates to avoidance, and (c) how this strategy impacts interpersonal behavior. Three studies examined these issues demonstrating that the more participants spontaneously self-distanced while reflecting on negative memories, the less emotional (Studies 1-3) and cardiovascular (Study 2) reactivity they displayed in the short term. Spontaneous self-distancing was also associated with lower emotional reactivity and intrusive ideation over time (Study 1). The negative association between spontaneous self-distancing and emotional reactivity was mediated by how participants construed their experience (i.e., less recounting relative to reconstruing) rather than avoidance (Studies 1-2). In addition, spontaneous self-distancing was associated with more problem-solving behavior and less reciprocation of negativity during conflicts among couples in ongoing relationships (Study 3). Although spontaneous self-distancing was empirically related to trait rumination, it explained unique variance in predicting key outcomes. 2010 APA, all rights reserved

A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates

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Shibata Darryl

2010-01-01

Full Text Available Abstract Background The purpose of this article is to present a relatively easy to understand cancer model where transformation occurs when the first cell, among many at risk within a colon, accumulates a set of driver mutations. The analysis of this model yields a simple algebraic equation, which takes as inputs the number of stem cells, mutation and division rates, and the number of driver mutations, and makes predictions about cancer epidemiology. Methods The equation [p = 1 - (1 - (1 - (1 - udkNm ] calculates the probability of cancer (p and contains five parameters: the number of divisions (d, the number of stem cells (N × m, the number of critical rate-limiting pathway driver mutations (k, and the mutation rate (u. In this model progression to cancer "starts" at conception and mutations accumulate with cell division. Transformation occurs when a critical number of rate-limiting pathway mutations first accumulates within a single stem cell. Results When applied to several colorectal cancer data sets, parameter values consistent with crypt stem cell biology and normal mutation rates were able to match the increase in cancer with aging, and the mutation frequencies found in cancer genomes. The equation can help explain how cancer risks may vary with age, height, germline mutations, and aspirin use. APC mutations may shorten pathways to cancer by effectively increasing the numbers of stem cells at risk. Conclusions The equation illustrates that age-related increases in cancer frequencies may result from relatively normal division and mutation rates. Although this equation does not encompass all of the known complexity of cancer, it may be useful, especially in a teaching setting, to help illustrate relationships between small and large cancer features.

Strong effects of ionizing radiation from Chernobyl on mutation rates

OpenAIRE

M?ller, Anders Pape; Mousseau, Timothy A.

2015-01-01

In this paper we use a meta-analysis to examine the relationship between radiation and mutation rates in Chernobyl across 45 published studies, covering 30 species. Overall effect size of radiation on mutation rates estimated as Pearson's product-moment correlation coefficient was very large (E = 0.67; 95% confidence intervals (CI) 0.59 to 0.73), accounting for 44.3% of the total variance in an unstructured random-effects model. Fail-safe calculations reflecting the number of unpublished null...

Smart Electrochemical Energy Storage Devices with Self-Protection and Self-Adaptation Abilities.

Science.gov (United States)

Yang, Yun; Yu, Dandan; Wang, Hua; Guo, Lin

2017-12-01

Currently, with booming development and worldwide usage of rechargeable electrochemical energy storage devices, their safety issues, operation stability, service life, and user experience are garnering special attention. Smart and intelligent energy storage devices with self-protection and self-adaptation abilities aiming to address these challenges are being developed with great urgency. In this Progress Report, we highlight recent achievements in the field of smart energy storage systems that could early-detect incoming internal short circuits and self-protect against thermal runaway. Moreover, intelligent devices that are able to take actions and self-adapt in response to external mechanical disruption or deformation, i.e., exhibiting self-healing or shape-memory behaviors, are discussed. Finally, insights into the future development of smart rechargeable energy storage devices are provided. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-adaptive phosphor coating technology for wafer-level scale chip packaging

International Nuclear Information System (INIS)

Zhou Linsong; Rao Haibo; Wang Wei; Wan Xianlong; Liao Junyuan; Wang Xuemei; Zhou Da; Lei Qiaolin

2013-01-01

A new self-adaptive phosphor coating technology has been successfully developed, which adopted a slurry method combined with a self-exposure process. A phosphor suspension in the water-soluble photoresist was applied and exposed to LED blue light itself and developed to form a conformal phosphor coating with self-adaptability to the angular distribution of intensity of blue light and better-performing spatial color uniformity. The self-adaptive phosphor coating technology had been successfully adopted in the wafer surface to realize a wafer-level scale phosphor conformal coating. The first-stage experiments show satisfying results and give an adequate demonstration of the flexibility of self-adaptive coating technology on application of WLSCP. (semiconductor devices)

The rate of spontaneous mutations in human myeloid cells

International Nuclear Information System (INIS)

Araten, David J.; Krejci, Ondrej; DiTata, Kimberly; Wunderlich, Mark; Sanders, Katie J.; Zamechek, Leah; Mulloy, James C.

2013-01-01

Highlights: • We provide the first measurement of the mutation rate (μ) in human myeloid cells. • μ is measured to be 3.6–23 × 10 −7 per cell division. • The AML-ETO and MLL-AF9 fusions do not seem to increase μ. • Cooperating mutations in NRAS, FLT3 and p53 not seem to increase μ. • Hypermutability may be required to explain leukemogenesis. - Abstract: The mutation rate (μ) is likely to be a key parameter in leukemogenesis, but historically, it has been difficult to measure in humans. The PIG-A gene has some advantages for the detection of spontaneous mutations because it is X-linked, and therefore only one mutation is required to disrupt its function. Furthermore, the PIG-A-null phenotype is readily detected by flow cytometry. Using PIG-A, we have now provided the first in vitro measurement of μ in myeloid cells, using cultures of CD34+ cells that are transduced with either the AML-ETO or the MLL-AF9 fusion genes and expanded with cytokines. For the AML-ETO cultures, the median μ value was ∼9.4 × 10 −7 (range ∼3.6–23 × 10 −7 ) per cell division. In contrast, few spontaneous mutations were observed in the MLL-AF9 cultures. Knockdown of p53 or introduction of mutant NRAS or FLT3 alleles did not have much of an effect on μ. Based on these data, we provide a model to predict whether hypermutability must occur in the process of leukemogenesis

Fixation probability of a nonmutator in a large population of asexual mutators.

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Jain, Kavita; James, Ananthu

2017-11-21

In an adapted population of mutators in which most mutations are deleterious, a nonmutator that lowers the mutation rate is under indirect selection and can sweep to fixation. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large population of asexual mutators. We show that when beneficial mutations are absent, the fixation probability is a nonmonotonic function of the mutation rate of the mutator: it first increases sublinearly and then decreases exponentially. We also find that beneficial mutations can enhance the fixation probability of a nonmutator. Our analysis is relevant to an understanding of recent experiments in which a reduction in the mutation rates has been observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation-induced cell mutations as a function of dose rate

International Nuclear Information System (INIS)

Kiefer, J.

1987-01-01

A brief review of the data in the literature is presented and forms the background of the experimental data given by the author obtained with exponential long-term cultures of V79 hamster cells exposed over a period of up to 35 days to different dose rates of gamma radiation. The experimental results show that at a dose rate of 40 mGy/hour the number of induced mutations is reduced, - which is in agreement with literature data - , but a dose rate of less than 30 mGy/hour makes the induced mutations leap to a value clearly higher than those induced by acute irradiation. As in addition to the mutations recombination is a significant factor of the radiation risk, experiments with a heterozygotic yeast strain have been made, as there is to date no reliable mammalian cell system available for this kind of research. Long-term radiation exposure of the yeast cells over a period of six weeks drastically increased the rate of recombinations, to a value higher by a factor of about 4 than that induced by acute irradiation. (orig.) [de

Frequent beneficial mutations during single-colony serial transfer of Streptococcus pneumoniae.

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Kathleen E Stevens

2011-08-01

Full Text Available The appearance of new mutations within a population provides the raw material for evolution. The consistent decline in fitness observed in classical mutation accumulation studies has provided support for the long-held view that deleterious mutations are more common than beneficial mutations. Here we present results of a study using a mutation accumulation design with the bacterium Streptococcus pneumoniae in which the fitness of the derived populations increased. This rise in fitness was associated specifically with adaptation to survival during brief stationary phase periods between single-colony population bottlenecks. To understand better the population dynamics behind this unanticipated adaptation, we developed a maximum likelihood model describing the processes of mutation and stationary-phase selection in the context of frequent population bottlenecks. Using this model, we estimate that the rate of beneficial mutations may be as high as 4.8×10(-4 events per genome for each time interval corresponding to the pneumococcal generation time. This rate is several orders of magnitude higher than earlier estimates of beneficial mutation rates in bacteria but supports recent results obtained through the propagation of small populations of Escherichia coli. Our findings indicate that beneficial mutations may be relatively frequent in bacteria and suggest that in S. pneumoniae, which develops natural competence for transformation, a steady supply of such mutations may be available for sampling by recombination.

Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations.

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Hsin-Hung Chou

2014-02-01

Full Text Available How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation.

Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

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Konstantin A Tsetsarkin

2009-08-01

Full Text Available Between 2005 and 2007 Chikungunya virus (CHIKV caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982 does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions

DySOA : Making service systems self-adaptive

NARCIS (Netherlands)

Siljee, J; Bosloper, [No Value; Nijhuis, J; Hammer, D; Benatallah, B; Casati, F; Traverso, P

2005-01-01

Service-centric systems exist in a very dynamic environment. This requires these systems to adapt at runtime in order to keep fulfilling their QoS. In order to create self-adaptive service systems, developers should not only design the service architecture, but also need to design the

Inter-disciplinary approach to selection in mutation breeding in local sorghums for adaptation and disease resistance

International Nuclear Information System (INIS)

Murty, B.R.; Taborda, F.; Reinoso, A.

1984-01-01

The present report of Mutational rectifications in local Sorghums involved improvement in adaptation and disease resistance. After seed treatment at 20, 30 and 40 kr the material now in the M 6 generation has given promising response to the above selection. Similarly, chemical mutagens with Na Azide + 5 kr γ-radiation of seeds also gave valuable mutants now in M 4 generation. More than 20 promising mutants are isolated with dwarf habit (100-125 cms), good head size, resistance to charcoal rot, good seed size and root development, more heads/unit area and yield increases (40%-100%) over the parents and much higher than the hybrids under cultivation. The mutants were also superior or equal to the parent in micronutrient uptake (Zn), protein content, nutrient uptake, light interception, photo-synthetic rate, and transfer to grain for N and P, root activities, regeneration capacity and disease resistance under artificial inoculation with better yield potential under close spacing (50 cm x 10 cm vs 75 cm x 10 cm). The multilocation test for wide adaptation in 3 locations revealed that at least 4 of the mutants have a wide range of adaptation. Biochemical studies of seed proteins by gel electrophoresis revealed distinct differences between the mutants and also the parents. Similar results were obtained for tannin content, Zn, phosphate (p 32 tracer) N uptake, indicating the presence of diverse mechanisms of adaptation and yield. Differences between the mutants in tillering, regeneration capacity rooting pattern, panicle no. and size, grain size and threshing % were observed. The integrated selection for the above attributes from M 3 to M 6 involved both field and laboratory testing demonstrating the utility of interdisciplinary approach in mutation breeding for effective selection in problem areas with complex ecological conditions and cropping patterns. The results of these studies are discussed with emphasis on selection methodology for the multiple traits involving

Indirect adaptive fuzzy wavelet neural network with self- recurrent consequent part for AC servo system.

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Hou, Runmin; Wang, Li; Gao, Qiang; Hou, Yuanglong; Wang, Chao

2017-09-01

This paper proposes a novel indirect adaptive fuzzy wavelet neural network (IAFWNN) to control the nonlinearity, wide variations in loads, time-variation and uncertain disturbance of the ac servo system. In the proposed approach, the self-recurrent wavelet neural network (SRWNN) is employed to construct an adaptive self-recurrent consequent part for each fuzzy rule of TSK fuzzy model. For the IAFWNN controller, the online learning algorithm is based on back propagation (BP) algorithm. Moreover, an improved particle swarm optimization (IPSO) is used to adapt the learning rate. The aid of an adaptive SRWNN identifier offers the real-time gradient information to the adaptive fuzzy wavelet neural controller to overcome the impact of parameter variations, load disturbances and other uncertainties effectively, and has a good dynamic. The asymptotical stability of the system is guaranteed by using the Lyapunov method. The result of the simulation and the prototype test prove that the proposed are effective and suitable. Copyright © 2017. Published by Elsevier Ltd.

Mutation rates at 42 Y chromosomal short tandem repeats in Chinese Han population in Eastern China.

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Wu, Weiwei; Ren, Wenyan; Hao, Honglei; Nan, Hailun; He, Xin; Liu, Qiuling; Lu, Dejian

2018-01-31

Mutation analysis of 42 Y chromosomal short tandem repeats (Y-STRs) loci was performed using a sample of 1160 father-son pairs from the Chinese Han population in Eastern China. The results showed that the average mutation rate across the 42 Y-STR loci was 0.0041 (95% CI 0.0036-0.0047) per locus per generation. The locus-specific mutation rates varied from 0.000 to 0.0190. No mutation was found at DYS388, DYS437, DYS448, DYS531, and GATA_H4. DYS627, DYS570, DYS576, and DYS449 could be classified as rapidly mutating Y-STRs, with mutation rates higher than 1.0 × 10 -2 . DYS458, DYS630, and DYS518 were moderately mutating Y-STRs, with mutation rates ranging from 8 × 10 -3 to 1 × 10 -2 . Although the characteristics of the Y-STR mutations were consistent with those in previous studies, mutation rate differences between our data and previous published data were found at some rapidly mutating Y-STRs. The single-copy loci located on the short arm of the Y chromosome (Yp) showed relatively higher mutation rates more frequently than the multi-copy loci. These results will not only extend the data for Y-STR mutations but also be important for kinship analysis, paternal lineage identification, and family relationship reconstruction in forensic Y-STR analysis.

A Convergent Differential Evolution Algorithm with Hidden Adaptation Selection for Engineering Optimization

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Zhongbo Hu

2014-01-01

Full Text Available Many improved differential Evolution (DE algorithms have emerged as a very competitive class of evolutionary computation more than a decade ago. However, few improved DE algorithms guarantee global convergence in theory. This paper developed a convergent DE algorithm in theory, which employs a self-adaptation scheme for the parameters and two operators, that is, uniform mutation and hidden adaptation selection (haS operators. The parameter self-adaptation and uniform mutation operator enhance the diversity of populations and guarantee ergodicity. The haS can automatically remove some inferior individuals in the process of the enhancing population diversity. The haS controls the proposed algorithm to break the loop of current generation with a small probability. The breaking probability is a hidden adaptation and proportional to the changes of the number of inferior individuals. The proposed algorithm is tested on ten engineering optimization problems taken from IEEE CEC2011.

Critical mutation rate has an exponential dependence on population size in haploid and diploid populations.

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Elizabeth Aston

Full Text Available Understanding the effect of population size on the key parameters of evolution is particularly important for populations nearing extinction. There are evolutionary pressures to evolve sequences that are both fit and robust. At high mutation rates, individuals with greater mutational robustness can outcompete those with higher fitness. This is survival-of-the-flattest, and has been observed in digital organisms, theoretically, in simulated RNA evolution, and in RNA viruses. We introduce an algorithmic method capable of determining the relationship between population size, the critical mutation rate at which individuals with greater robustness to mutation are favoured over individuals with greater fitness, and the error threshold. Verification for this method is provided against analytical models for the error threshold. We show that the critical mutation rate for increasing haploid population sizes can be approximated by an exponential function, with much lower mutation rates tolerated by small populations. This is in contrast to previous studies which identified that critical mutation rate was independent of population size. The algorithm is extended to diploid populations in a system modelled on the biological process of meiosis. The results confirm that the relationship remains exponential, but show that both the critical mutation rate and error threshold are lower for diploids, rather than higher as might have been expected. Analyzing the transition from critical mutation rate to error threshold provides an improved definition of critical mutation rate. Natural populations with their numbers in decline can be expected to lose genetic material in line with the exponential model, accelerating and potentially irreversibly advancing their decline, and this could potentially affect extinction, recovery and population management strategy. The effect of population size is particularly strong in small populations with 100 individuals or less; the

Adaptive threshold control for auto-rate fallback algorithm in IEEE 802.11 multi-rate WLANs

Science.gov (United States)

Wu, Qilin; Lu, Yang; Zhu, Xiaolin; Ge, Fangzhen

2012-03-01

The IEEE 802.11 standard supports multiple rates for data transmission in the physical layer. Nowadays, to improve network performance, a rate adaptation scheme called auto-rate fallback (ARF) is widely adopted in practice. However, ARF scheme suffers performance degradation in multiple contending nodes environments. In this article, we propose a novel rate adaptation scheme called ARF with adaptive threshold control. In multiple contending nodes environment, the proposed scheme can effectively mitigate the frame collision effect on rate adaptation decision by adaptively adjusting rate-up and rate-down threshold according to the current collision level. Simulation results show that the proposed scheme can achieve significantly higher throughput than the other existing rate adaptation schemes. Furthermore, the simulation results also demonstrate that the proposed scheme can effectively respond to the varying channel condition.

Parallel Monitors for Self-adaptive Sessions

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Mario Coppo

2016-06-01

Full Text Available The paper presents a data-driven model of self-adaptivity for multiparty sessions. System choreography is prescribed by a global type. Participants are incarnated by processes associated with monitors, which control their behaviour. Each participant can access and modify a set of global data, which are able to trigger adaptations in the presence of critical changes of values. The use of the parallel composition for building global types, monitors and processes enables a significant degree of flexibility: an adaptation step can dynamically reconfigure a set of participants only, without altering the remaining participants, even if the two groups communicate.

Bibliography. Examples of literature related to the use of induced mutations in cross-breeding

International Nuclear Information System (INIS)

Micke, A.

1976-01-01

The bibliography contains about 400 references arranged alphabetically under the following 20 headings: Genetic analysis of mutants; Mutant gene combination and interaction; Pleiotropy versus linkage; Genetic background; Heterosis and overdominance; Mutations in heterozygous plants such as vegetatively propagated plants; Mutations in hybrids of self-pollinators; Distant hybridization; Increasing recombination; Alteration in the reproductive system; Alteration of photoperiodic response; Self and cross-incompatibility; Male or female sterility; Adaptability of mutants and mutant hybrids; Mutation induction in cross pollinators; Dwarfing mutant genes in cross-breeding; Protein mutants in cross-breeding; Disease resistant mutants in cross-breeding; Practical cross-breeding programmes using mutants; Spontaneous versus induced genetic diversity

Non-uniform Mutation Rates for Problems with Unknown Solution Lengths

DEFF Research Database (Denmark)

Cathabard, Stephan; Lehre, Per Kristian; Yao, Xin

2011-01-01

Many practical optimisation problems allow candidate solu- tions of varying lengths, and where the length of the opti- mal solution is thereby a priori unknown. We suggest that non-uniform mutation rates can be beneficial when solving such problems. In particular, we consider a mutation oper- ator...... that flips each bit with a probability that is inversely proportional to the bit position, rather than the bitstring length. The runtime of the (1+1) EA using this mutation operator is analysed rigorously on standard example func- tions. Furthermore, the behaviour of the new mutation op- erator...... distribution, and show that the new operator can yield exponentially faster runtimes for some parameters of this distribution. The experimental results show that the new mutation operator leads to dramatically shorter runtimes on a class of instances of the software engi- neering problem that is conjectured...

A chaos wolf optimization algorithm with self-adaptive variable step-size

Science.gov (United States)

Zhu, Yong; Jiang, Wanlu; Kong, Xiangdong; Quan, Lingxiao; Zhang, Yongshun

2017-10-01

To explore the problem of parameter optimization for complex nonlinear function, a chaos wolf optimization algorithm (CWOA) with self-adaptive variable step-size was proposed. The algorithm was based on the swarm intelligence of wolf pack, which fully simulated the predation behavior and prey distribution way of wolves. It possessed three intelligent behaviors such as migration, summons and siege. And the competition rule as "winner-take-all" and the update mechanism as "survival of the fittest" were also the characteristics of the algorithm. Moreover, it combined the strategies of self-adaptive variable step-size search and chaos optimization. The CWOA was utilized in parameter optimization of twelve typical and complex nonlinear functions. And the obtained results were compared with many existing algorithms, including the classical genetic algorithm, the particle swarm optimization algorithm and the leader wolf pack search algorithm. The investigation results indicate that CWOA possess preferable optimization ability. There are advantages in optimization accuracy and convergence rate. Furthermore, it demonstrates high robustness and global searching ability.

Adaptation in the fuzzy self-organising controller

DEFF Research Database (Denmark)

Jantzen, Jan; Poulsen, Niels Kjølstad

2003-01-01

This simulation study provides an analysis of the adaptation mechanism in the self-organising fuzzy controller, SOC. The approach is to apply a traditional adaptive control viewpoint. A simplified performance measure in the SOC controller is used in a loss function, and thus the MIT rule implies...... an update mechanism similar to the SOC update mechanism. Two simulations of proportionally controlled systems show the behaviour of the proportional gain as it adapts to a specified behaviour....

Determinants of self-rated health: could health status explain the association between self-rated health and mortality?

Science.gov (United States)

Murata, Chiyoe; Kondo, Takaaki; Tamakoshi, Koji; Yatsuya, Hiroshi; Toyoshima, Hideaki

2006-01-01

The purpose of this study was to investigate factors related to self-rated health and to mortality among 2490 community-living elderly. Respondents were followed for 7.3 years for all-cause mortality. To compare the relative impact of each variable, we employed logistic regression analysis for self-rated health and Cox hazard analysis for mortality. Cox analysis stratified by gender, follow-up periods, age group, and functional status was also employed. Series of analysis found that factors associated with self-rated health and with mortality were not identical. Psychological factors such as perceived isolation at home or 'ikigai (one aspect of psychological well-being)' were associated with self-rated health only. Age, functional status, and social relations were associated both with self-rated health and mortality after controlling for possible confounders. Illnesses and functional status accounted for 35-40% of variances in the fair/poor self-rated health. Differences by gender and functional status were observed in the factors related to self-rated health. Overall, self-rated health effect on mortality was stronger for people with no functional impairment, for shorter follow-up period, and for young-old age group. Although, illnesses and functional status were major determinants of self-rated health, economical, psychological, and social factors were also related to self-rated health.

Effects of Germline Mutations in the Ras/MAPK Signaling Pathway on Adaptive Behavior: Cardiofaciocutaneous Syndrome and Noonan Syndrome

Science.gov (United States)

Pierpont, Elizabeth I.; Pierpont, Mary Ella; Mendelsohn, Nancy J.; Roberts, Amy E.; Tworog-Dube, Erica; Rauen, Katherine A.; Seidenberg, Mark S.

2011-01-01

Cardiofaciocutaneous syndrome (CFC) and Noonan syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1 and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS and RAF1 typically cause NS. Although both syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/MAPK pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive ability in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes. PMID:20186801

Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident

International Nuclear Information System (INIS)

Dubrova, Yuri E.; Buard, Jerome; Jeffreys, Alec J.; Nesterov, Valeri N.; Krouchinsky, Nicolay G.; Ostapenko, Vladislav A.; Vergnaud, Gilles; Giraudeau, Fabienne

1997-01-01

Analysis of germline mutation rate at human minisatellites among children born in areas of the Mogilev district of Belarus heavily polluted after the Chernobyl accident has been extended, both by recruiting more families from the affected region and by using five additional minisatellite probes, including multi-locus probe 33.6 and four hypervariable single-locus probes. These additional data confirmed a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. An elevated rate was seen at all three independent sets of minisatellites (detected separately by multi-locus probes 33.15, 33.6 and six single-locus probes), indicating a generalised increase in minisatellite germline mutation rate in the Belarus families. Within the Belarus cohort, mutation rate was significantly greater in families with higher parental radiation dose estimated for chronic external and internal exposure to caesium-137, consistent with radiation induction of germline mutation. The spectra of mutation seen in the unexposed and exposed families were indistinguishable, suggesting that increased mutation observed over multiple loci arises indirectly by some mechanism that enhances spontaneous minisatellite mutation

Molecular dynamics of mesophilic-like mutants of a cold-adapted enzyme: insights into distal effects induced by the mutations.

Directory of Open Access Journals (Sweden)

Elena Papaleo

Full Text Available Networks and clusters of intramolecular interactions, as well as their "communication" across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme.

Self-rated function, self-rated health, and postmortem evidence of brain infarcts: findings from the Nun Study.

Science.gov (United States)

Greiner, P A; Snowdon, D A; Greiner, L H

1999-07-01

Self-rated function is a new global measure. Previous findings suggest that self-rated function predicts future functional decline and is strongly associated with all-cause mortality. We hypothesized that the strength of the relationship of self-rated function to all-cause mortality was in part due to functional decline, such as would occur with brain infarcts. Self-ratings of function and health (on a 5-point scale, ranging from excellent to poor) were assessed annually on 630 participants in the Nun Study. Mortality surveillance extended from October 31, 1991 to March 1, 1998, and, among those who died, neuropathological examination determined postmortem evidence of brain infarcts. Cox regression modeling with self-rated function and health as time-dependent covariates and stratification by assessment period were used in these analyses. Self-rated function and health ratings of good, fair, and poor were significantly associated with doubling of the risk of mortality, compared with ratings of very good and excellent. Self-rated function ratings of fair or poor were associated with a threefold increase in the risk of mortality with brain infarcts, but self-rated function and health ratings of fair and poor were comparable in their association with all-cause mortality and mortality without brain infarcts. Self-rated function was significantly associated with mortality with brain infarcts, suggesting that brain infarcts may be experienced as functional loss but not recognized or labeled as disease. Our results suggest that self-rated function and health should be explored simultaneously in future research.

Single genome retrieval of context-dependent variability in mutation rates for human germline.

Science.gov (United States)

Sahakyan, Aleksandr B; Balasubramanian, Shankar

2017-01-13

Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database. Due to the nature of the method design and the imposed stringency criteria, we expect our rate constants to be good estimates for the rates of spontaneous mutations. Benefiting from such data, we study the short-range nucleotide (up to 7-mer) organisation and the germline basal substitution propensity (BSP) profile of the human genome; characterise novel, CpG-independent, substitution prone and resistant motifs; confirm a decreased tendency of moieties with low BSP to undergo somatic mutations in a number of cancer types; and, produce a Trek-based estimate of the overall mutation rate in human. The extended set of rate constants we report may enrich our resources and help advance our understanding of genome dynamics and evolution, with possible implications for the role of spontaneous mutations in the emergence of pathological genotypes and neutral evolution of proteomes.

Strong effects of ionizing radiation from Chernobyl on mutation rates.

Science.gov (United States)

Møller, Anders Pape; Mousseau, Timothy A

2015-02-10

In this paper we use a meta-analysis to examine the relationship between radiation and mutation rates in Chernobyl across 45 published studies, covering 30 species. Overall effect size of radiation on mutation rates estimated as Pearson's product-moment correlation coefficient was very large (E = 0.67; 95% confidence intervals (CI) 0.59 to 0.73), accounting for 44.3% of the total variance in an unstructured random-effects model. Fail-safe calculations reflecting the number of unpublished null results needed to eliminate this average effect size showed the extreme robustness of this finding (Rosenberg's method: 4135 at p = 0.05). Indirect tests did not provide any evidence of publication bias. The effect of radiation on mutations varied among taxa, with plants showing a larger effect than animals. Humans were shown to have intermediate sensitivity of mutations to radiation compared to other species. Effect size did not decrease over time, providing no evidence for an improvement in environmental conditions. The surprisingly high mean effect size suggests a strong impact of radioactive contamination on individual fitness in current and future generations, with potentially significant population-level consequences, even beyond the area contaminated with radioactive material.

Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection.

Directory of Open Access Journals (Sweden)

Irene Bianconi

2011-02-01

Full Text Available The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF patients. Persistent lifestyle is established with P. aeruginosa patho-adaptive variants, which are clonal with the initially-acquired strains. Several reports indicated that P. aeruginosa adapts by loss-of-function mutations which enhance fitness in CF airways and sustain its clonal expansion during chronic infection. To validate this model of P. aeruginosa adaptation to CF airways and to identify novel genes involved in this microevolution, we designed a novel approach of positive-selection screening by PCR-based signature-tagged mutagenesis (Pos-STM in a murine model of chronic airways infection. A systematic positive-selection scheme using sequential rounds of in vivo screenings for bacterial maintenance, as opposed to elimination, generated a list of genes whose inactivation increased the colonization and persistence in chronic airways infection. The phenotypes associated to these Pos-STM mutations reflect alterations in diverse aspects of P. aeruginosa biology which include lack of swimming and twitching motility, lack of production of the virulence factors such as pyocyanin, biofilm formation, and metabolic functions. In addition, Pos-STM mutants showed altered invasion and stimulation of immune response when tested in human respiratory epithelial cells, indicating that P. aeruginosa is prone to revise the interaction with its host during persistent lifestyle. Finally, sequence analysis of Pos-STM genes in longitudinally P. aeruginosa isolates from CF patients identified signs of patho-adaptive mutations within the genome. This novel Pos-STM approach identified bacterial functions that can have important clinical implications for the persistent lifestyle and disease progression of the airway chronic infection.

What does self rated mental health represent

Directory of Open Access Journals (Sweden)

Daphna Levinson

2014-12-01

Full Text Available Background. Unlike the widely used self rated health, the self rated mental health was found unsuitable as a proxy for mental illness. This paper analyses the relationships between the self ratings of physical health, mental health and overall health, and their association of with the objective indicators for physical and mental health. Design and methods. The study is a secondary analysis of data from a nationwide representative sample of the non-institutionalized adult residents of Israel in 2003 that was collected via computer-assisted personal interview methods [n=4859].Results. The self rated physical health and the self rated mental health were strongly related to each other yet the self rated mental health was not related to chronic physical conditions and the self rated physical health was not related to mental disorders. In a multiple logistic regression analysis, those with positive self rated mental health had 93 times the odds of reporting positive overall health whereas those with positive self rated physical health had 40 times the odds of reporting positive overall health. Conclusions. The self rating of mental health presents a qualitatively different dimension from mental illness. The self rated mental health is two times more important than the self rated physical health in predicting the self rated overall health

Multiplex fluorescence melting curve analysis for mutation detection with dual-labeled, self-quenched probes.

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Qiuying Huang

2011-04-01

Full Text Available Probe-based fluorescence melting curve analysis (FMCA is a powerful tool for mutation detection based on melting temperature generated by thermal denaturation of the probe-target hybrid. Nevertheless, the color multiplexing, probe design, and cross-platform compatibility remain to be limited by using existing probe chemistries. We hereby explored two dual-labeled, self-quenched probes, TaqMan and shared-stem molecular beacons, in their ability to conduct FMCA. Both probes could be directly used for FMCA and readily integrated with closed-tube amplicon hybridization under asymmetric PCR conditions. Improved flexibility of FMCA by using these probes was illustrated in three representative applications of FMCA: mutation scanning, mutation identification and mutation genotyping, all of which achieved improved color-multiplexing with easy probe design and versatile probe combination and all were validated with a large number of real clinical samples. The universal cross-platform compatibility of these probes-based FMCA was also demonstrated by a 4-color mutation genotyping assay performed on five different real-time PCR instruments. The dual-labeled, self-quenched probes offered unprecedented combined advantage of enhanced multiplexing, improved flexibility in probe design, and expanded cross-platform compatibility, which would substantially improve FMCA in mutation detection of various applications.

Predicting protein folding rate change upon point mutation using residue-level coevolutionary information.

Science.gov (United States)

Mallik, Saurav; Das, Smita; Kundu, Sudip

2016-01-01

Change in folding kinetics of globular proteins upon point mutation is crucial to a wide spectrum of biological research, such as protein misfolding, toxicity, and aggregations. Here we seek to address whether residue-level coevolutionary information of globular proteins can be informative to folding rate changes upon point mutations. Generating residue-level coevolutionary networks of globular proteins, we analyze three parameters: relative coevolution order (rCEO), network density (ND), and characteristic path length (CPL). A point mutation is considered to be equivalent to a node deletion of this network and respective percentage changes in rCEO, ND, CPL are found linearly correlated (0.84, 0.73, and -0.61, respectively) with experimental folding rate changes. The three parameters predict the folding rate change upon a point mutation with 0.031, 0.045, and 0.059 standard errors, respectively. © 2015 Wiley Periodicals, Inc.

The rate and effects of spontaneous mutation on fitness traits in the social amoeba, Dictyostelium discoideum.

Science.gov (United States)

Hall, David W; Fox, Sara; Kuzdzal-Fick, Jennie J; Strassmann, Joan E; Queller, David C

2013-07-08

We performed a mutation accumulation (MA) experiment in the social amoeba Dictyostelium discoideum to estimate the rate and distribution of effects of spontaneous mutations affecting eight putative fitness traits. We found that the per-generation mutation rate for most fitness components is 0.0019 mutations per haploid genome per generation or larger. This rate is an order of magnitude higher than estimates for fitness components in the unicellular eukaryote Saccharomyces cerevisiae, even though the base-pair substitution rate is two orders of magnitude lower. The high rate of fitness-altering mutations observed in this species may be partially explained by a large mutational target relative to S. cerevisiae. Fitness-altering mutations also may occur primarily at simple sequence repeats, which are common throughout the genome, including in coding regions, and may represent a target that is particularly likely to give fitness effects upon mutation. The majority of mutations had deleterious effects on fitness, but there was evidence for a substantial fraction, up to 40%, being beneficial for some of the putative fitness traits. Competitive ability within the multicellular slug appears to be under weak directional selection, perhaps reflecting the fact that slugs are sometimes, but not often, comprised of multiple clones in nature. Evidence for pleiotropy among fitness components across MA lines was absent, suggesting that mutations tend to act on single fitness components.

Body Image Distortion and Exposure to Extreme Body Types: Contingent Adaptation and Cross Adaptation for Self and Other.

Science.gov (United States)

Brooks, Kevin R; Mond, Jonathan M; Stevenson, Richard J; Stephen, Ian D

2016-01-01

Body size misperception is common amongst the general public and is a core component of eating disorders and related conditions. While perennial media exposure to the "thin ideal" has been blamed for this misperception, relatively little research has examined visual adaptation as a potential mechanism. We examined the extent to which the bodies of "self" and "other" are processed by common or separate mechanisms in young women. Using a contingent adaptation paradigm, experiment 1 gave participants prolonged exposure to images both of the self and of another female that had been distorted in opposite directions (e.g., expanded other/contracted self), and assessed the aftereffects using test images both of the self and other. The directions of the resulting perceptual biases were contingent on the test stimulus, establishing at least some separation between the mechanisms encoding these body types. Experiment 2 used a cross adaptation paradigm to further investigate the extent to which these mechanisms are independent. Participants were adapted either to expanded or to contracted images of their own body or that of another female. While adaptation effects were largest when adapting and testing with the same body type, confirming the separation of mechanisms reported in experiment 1, substantial misperceptions were also demonstrated for cross adaptation conditions, demonstrating a degree of overlap in the encoding of self and other. In addition, the evidence of misperception of one's own body following exposure to "thin" and to "fat" others demonstrates the viability of visual adaptation as a model of body image disturbance both for those who underestimate and those who overestimate their own size.

Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.

Directory of Open Access Journals (Sweden)

Nicole Forbes

Full Text Available The NS1 protein of influenza A virus (IAV is a multifunctional virulence factor. We have previously characterized gain-of-function mutations in the NS1 protein arising from the experimental adaptation of the human isolate A/Hong Kong/1/1968(H3N2 (HK to the mouse. The majority of these mouse adapted NS1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation specificity factor 30 (CPSF30. Because nuclear trafficking is a major genetic determinant of influenza virus host adaptation, we assessed subcellular localization and host gene expression of NS1 adaptive mutations. Recombinant HK viruses with adaptive mutations in the NS1 gene were assessed for NS1 protein subcellular localization in mouse and human cells using confocal microscopy and cellular fractionation. In human cells the HK wild-type (HK-wt virus NS1 protein partitioned equivalently between the cytoplasm and nucleus but was defective in cytoplasmic localization in mouse cells. Several adaptive mutations increased the proportion of NS1 in the cytoplasm of mouse cells with the greatest effects for mutations M106I and D125G. The host gene expression profile of the adaptive mutants was determined by microarray analysis of infected mouse cells to show either high or low extents of host-gene regulation (HGR or LGR phenotypes. While host genes were predominantly down regulated for the HGR group of mutants (D2N, V23A, F103L, M106I+L98S, L98S, M106V, and M106V+M124I, the LGR phenotype mutants (D125G, M106I, V180A, V226I, and R227K were characterized by a predominant up regulation of host genes. CPSF30 binding affinity of NS1 mutants did not predict effects on host gene expression. To our knowledge this is the first report of roles of adaptive NS1 mutations that impact intracellular localization and regulation of host gene expression.

Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

Science.gov (United States)

Fernández, Lucía

2012-01-01

Summary: The substantial use of antibiotics in the clinic, combined with a dearth of new antibiotic classes, has led to a gradual increase in the resistance of bacterial pathogens to these compounds. Among the various mechanisms by which bacteria endure the action of antibiotics, those affecting influx and efflux are of particular importance, as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. This review evaluates the impact of porins and efflux pumps on two major types of resistance, namely, mutational and adaptive types of resistance, both of which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms. In particular, we explain how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics. The identification of porins and pumps as major resistance markers has opened new possibilities for the development of novel therapeutic strategies directed specifically against these mechanisms. PMID:23034325

Research on a Pulmonary Nodule Segmentation Method Combining Fast Self-Adaptive FCM and Classification

Directory of Open Access Journals (Sweden)

Hui Liu

2015-01-01

Full Text Available The key problem of computer-aided diagnosis (CAD of lung cancer is to segment pathologically changed tissues fast and accurately. As pulmonary nodules are potential manifestation of lung cancer, we propose a fast and self-adaptive pulmonary nodules segmentation method based on a combination of FCM clustering and classification learning. The enhanced spatial function considers contributions to fuzzy membership from both the grayscale similarity between central pixels and single neighboring pixels and the spatial similarity between central pixels and neighborhood and improves effectively the convergence rate and self-adaptivity of the algorithm. Experimental results show that the proposed method can achieve more accurate segmentation of vascular adhesion, pleural adhesion, and ground glass opacity (GGO pulmonary nodules than other typical algorithms.

Beyond Reactive Planning: Self Adaptive Software and Self Modeling Software in Predictive Deliberation Management

National Research Council Canada - National Science Library

Lenahan, Jack; Nash, Michael P; Charles, Phil

2008-01-01

.... We present the following hypothesis: predictive deliberation management using self-adapting and self-modeling software will be required to provide mission planning adjustments after the start of a mission...

Adaptive transition rates in excitable membranes

Directory of Open Access Journals (Sweden)

Shimon Marom

2009-02-01

Full Text Available Adaptation of activity in excitable membranes occurs over a wide range of timescales. Standard computational approaches handle this wide temporal range in terms of multiple states and related reaction rates emanating from the complexity of ionic channels. The study described here takes a different (perhaps complementary approach, by interpreting ion channel kinetics in terms of population dynamics. I show that adaptation in excitable membranes is reducible to a simple Logistic-like equation in which the essential non-linearity is replaced by a feedback loop between the history of activation and an adaptive transition rate that is sensitive to a single dimension of the space of inactive states. This physiologically measurable dimension contributes to the stability of the system and serves as a powerful modulator of input-output relations that depends on the patterns of prior activity; an intrinsic scale free mechanism for cellular adaptation that emerges from the microscopic biophysical properties of ion channels of excitable membranes.

Body Image Distortion and Exposure to Extreme Body Types: Contingent Adaptation and Cross Adaptation for Self and Other

Directory of Open Access Journals (Sweden)

Kevin R. Brooks

2016-07-01

Full Text Available Body size misperception is common amongst the general public and is a core component of eating disorders and related conditions. While perennial media exposure to the thin ideal has been blamed for this misperception, relatively little research has examined visual adaptation as a potential mechanism. We examined the extent to which the bodies of self and other are processed by common or separate mechanisms in young women. Using a contingent adaptation paradigm, experiment 1 gave participants prolonged exposure to images both of the self and of another female that had been distorted in opposite directions (e.g. expanded other/contracted self, and assessed the aftereffects using test images both of the self and other. The directions of the resulting perceptual biases were contingent on the test stimulus, establishing at least some separation between the mechanisms encoding these body types. Experiment 2 used a cross adaptation paradigm to further investigate the extent to which these mechanisms are independent. Participants were adapted either to expanded or to contracted images of their own body or that of another female. While adaptation effects were largest when adapting and testing with the same body type, confirming the separation of mechanisms reported in experiment 1, substantial misperceptions were also demonstrated for cross adaptation conditions, demonstrating a degree of overlap in the encoding of self and other. In addition, the evidence of misperception of one’s own body following exposure to thin and to fat others demonstrates the viability of visual adaptation as a model of body image disturbance both for those who underestimate and those who overestimate their own size.

From bad to good: Fitness reversals and the ascent of deleterious mutations.

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Matthew C Cowperthwaite

2006-10-01

Full Text Available Deleterious mutations are considered a major impediment to adaptation, and there are straightforward expectations for the rate at which they accumulate as a function of population size and mutation rate. In a simulation model of an evolving population of asexually replicating RNA molecules, initially deleterious mutations accumulated at rates nearly equal to that of initially beneficial mutations, without impeding evolutionary progress. As the mutation rate was increased within a moderate range, deleterious mutation accumulation and mean fitness improvement both increased. The fixation rates were higher than predicted by many population-genetic models. This seemingly paradoxical result was resolved in part by the observation that, during the time to fixation, the selection coefficient (s of initially deleterious mutations reversed to confer a selective advantage. Significantly, more than half of the fixations of initially deleterious mutations involved fitness reversals. These fitness reversals had a substantial effect on the total fitness of the genome and thus contributed to its success in the population. Despite the relative importance of fitness reversals, however, the probabilities of fixation for both initially beneficial and initially deleterious mutations were exceedingly small (on the order of 10(-5 of all mutations.

Effects of Sublethal Fungicides on Mutation Rates and Genomic Variation in Fungal Plant Pathogen, Sclerotinia sclerotiorum.

Science.gov (United States)

Amaradasa, B Sajeewa; Everhart, Sydney E

2016-01-01

when repeated, only one isolate had higher EC50 while most isolates showed no difference. Results of this support the hypothesis that sublethal fungicide stress increases mutation rates in a largely clonal plant pathogen under in vitro conditions. Collectively, this work will aid our understanding how non-lethal fungicide exposure may affect genomic variation, which may be an important mechanism of novel trait emergence, adaptation, and evolution for clonal organisms.

Effects of Sublethal Fungicides on Mutation Rates and Genomic Variation in Fungal Plant Pathogen, Sclerotinia sclerotiorum.

Directory of Open Access Journals (Sweden)

B Sajeewa Amaradasa

experiment, and when repeated, only one isolate had higher EC50 while most isolates showed no difference. Results of this support the hypothesis that sublethal fungicide stress increases mutation rates in a largely clonal plant pathogen under in vitro conditions. Collectively, this work will aid our understanding how non-lethal fungicide exposure may affect genomic variation, which may be an important mechanism of novel trait emergence, adaptation, and evolution for clonal organisms.

Effects of Sublethal Fungicides on Mutation Rates and Genomic Variation in Fungal Plant Pathogen, Sclerotinia sclerotiorum

Science.gov (United States)

Amaradasa, B. Sajeewa

2016-01-01

, and when repeated, only one isolate had higher EC50 while most isolates showed no difference. Results of this support the hypothesis that sublethal fungicide stress increases mutation rates in a largely clonal plant pathogen under in vitro conditions. Collectively, this work will aid our understanding how non-lethal fungicide exposure may affect genomic variation, which may be an important mechanism of novel trait emergence, adaptation, and evolution for clonal organisms. PMID:27959950

Adaptive disengagement buffers self-esteem from negative social feedback.

Science.gov (United States)

Leitner, Jordan B; Hehman, Eric; Deegan, Matthew P; Jones, James M

2014-11-01

The degree to which self-esteem hinges on feedback in a domain is known as a contingency of self-worth, or engagement. Although previous research has conceptualized engagement as stable, it would be advantageous for individuals to dynamically regulate engagement. The current research examined whether the tendency to disengage from negative feedback accounts for variability in self-esteem. We created the Adaptive Disengagement Scale (ADS) to capture individual differences in the tendency to disengage self-esteem from negative outcomes. Results demonstrated that the ADS is reliable and valid (Studies 1 and 2). Furthermore, in response to negative social feedback, higher scores on the ADS predicted greater state self-esteem (Study 3), and this relationship was mediated by disengagement (Study 4). These findings demonstrate that adaptive disengagement protects self-esteem from negative outcomes and that the ADS is a valid measure of individual differences in the implementation of this process. © 2014 by the Society for Personality and Social Psychology, Inc.

A chaos wolf optimization algorithm with self-adaptive variable step-size

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Yong Zhu

2017-10-01

Full Text Available To explore the problem of parameter optimization for complex nonlinear function, a chaos wolf optimization algorithm (CWOA with self-adaptive variable step-size was proposed. The algorithm was based on the swarm intelligence of wolf pack, which fully simulated the predation behavior and prey distribution way of wolves. It possessed three intelligent behaviors such as migration, summons and siege. And the competition rule as “winner-take-all” and the update mechanism as “survival of the fittest” were also the characteristics of the algorithm. Moreover, it combined the strategies of self-adaptive variable step-size search and chaos optimization. The CWOA was utilized in parameter optimization of twelve typical and complex nonlinear functions. And the obtained results were compared with many existing algorithms, including the classical genetic algorithm, the particle swarm optimization algorithm and the leader wolf pack search algorithm. The investigation results indicate that CWOA possess preferable optimization ability. There are advantages in optimization accuracy and convergence rate. Furthermore, it demonstrates high robustness and global searching ability.

Graduate employability capacities, self-esteem and career adaptability among South African young adults

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Sadika Ismail

2017-08-01

Full Text Available Orientation: Employers expect young graduates to have a well-rounded sense of self, to display a range of graduate employability capacities and to adapt to constant changes they are faced with in order to obtain and maintain employment. Research purpose: The goals of this study are (1 to investigate whether a significant relationship exists between graduate employability capacities, self-esteem and career adaptability, (2 to ascertain if a set of graduate employability capacities, when combined with self-esteem, has a significant relationship with a set of career adaptability capacities and (3 to identify the major variables that contribute to this relationship. Motivation for the study: The potential for career adaptability, graduate employability capacities and self-esteem of young adults promotes employability among graduates, thereby addressing and possibly reducing youth unemployment in South Africa. Research approach, design and method: A quantitative, cross-sectional research design approach was utilised in which descriptive statistics, Pearson product-moment correlations and canonical correlation analysis were employed to accomplish the objectives of this study. Respondents (N = 332 were enrolled at further education and training (FET colleges and were predominantly black (98.5% and female (62% students between the ages of 18 and 29. Main findings: The results displayed positive multivariate relationships between the variables and furthermore showed that graduate employability capacities contributed the most in terms of clarifying the respondents’ career adaptability as compared to their self-esteem. Practical and managerial implications: This study proposes that young adults’ career adaptability can be enhanced through the development of their self-esteem and particularly their graduate employability capacities, thus making them more employable. Contributions: Theoretically, this study proves useful because of the significant

Neural predictors of sensorimotor adaptation rate and savings.

Science.gov (United States)

Cassady, Kaitlin; Ruitenberg, Marit; Koppelmans, Vincent; Reuter-Lorenz, Patricia; De Dios, Yiri; Gadd, Nichole; Wood, Scott; Riascos Castenada, Roy; Kofman, Igor; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

2018-04-01

In this study, we investigate whether individual variability in the rate of visuomotor adaptation and multiday savings is associated with differences in regional gray matter volume and resting-state functional connectivity. Thirty-four participants performed a manual adaptation task during two separate test sessions, on average 9 days apart. Functional connectivity strength between sensorimotor, dorsal cingulate, and temporoparietal regions of the brain was found to predict the rate of learning during the early phase of the adaptation task. In contrast, default mode network connectivity strength was found to predict both the rate of learning during the late adaptation phase and savings. As for structural predictors, greater gray matter volume in temporoparietal and occipital regions predicted faster early learning, whereas greater gray matter volume in superior posterior regions of the cerebellum predicted faster late learning. These findings suggest that the offline neural predictors of early adaptation may facilitate the cognitive aspects of sensorimotor adaptation, supported by the involvement of temporoparietal and cingulate networks. The offline neural predictors of late adaptation and savings, including the default mode network and the cerebellum, likely support the storage and modification of newly acquired sensorimotor representations. © 2017 Wiley Periodicals, Inc.

A novel pseudoderivative-based mutation operator for real-coded adaptive genetic algorithms [v2; ref status: indexed, http://f1000r.es/1td

OpenAIRE

Maxinder S Kanwal; Avinash S Ramesh; Lauren A Huang

2013-01-01

Recent development of large databases, especially those in genetics and proteomics, is pushing the development of novel computational algorithms that implement rapid and accurate search strategies. One successful approach has been to use artificial intelligence and methods, including pattern recognition (e.g. neural networks) and optimization techniques (e.g. genetic algorithms). The focus of this paper is on optimizing the design of genetic algorithms by using an adaptive mutation rate that ...

How much do genetic covariances alter the rate of adaptation?

Science.gov (United States)

Agrawal, Aneil F; Stinchcombe, John R

2009-03-22

Genetically correlated traits do not evolve independently, and the covariances between traits affect the rate at which a population adapts to a specified selection regime. To measure the impact of genetic covariances on the rate of adaptation, we compare the rate fitness increases given the observed G matrix to the expected rate if all the covariances in the G matrix are set to zero. Using data from the literature, we estimate the effect of genetic covariances in real populations. We find no net tendency for covariances to constrain the rate of adaptation, though the quality and heterogeneity of the data limit the certainty of this result. There are some examples in which covariances strongly constrain the rate of adaptation but these are balanced by counter examples in which covariances facilitate the rate of adaptation; in many cases, covariances have little or no effect. We also discuss how our metric can be used to identify traits or suites of traits whose genetic covariances to other traits have a particularly large impact on the rate of adaptation.

Low Base-Substitution Mutation Rate in the Germline Genome of the Ciliate Tetrahymena thermophila

Science.gov (United States)

2016-09-15

Tetrahymena thermophila, a model eukaryote. PLoS Biol. 4:e286. Farlow A, et al. 2015. The spontaneous mutation rate in the fission yeast Schizosaccharomyces...spontane- ous mutations in yeast . Proc Natl Acad Sci U S A. 105:9272–9277. Lynn DH, Doerder FP. 2012. The life and times of Tetrahymena. Methods Cell...Low Base-Substitution Mutation Rate in the Germline Genome of the Ciliate Tetrahymena thermophila Hongan Long1,2,y, David J. Winter3,*,y, Allan Y.-C

The impact of culture on adaptive versus maladaptive self-reflection.

Science.gov (United States)

Grossmann, Igor; Kross, Ethan

2010-08-01

Although recent findings indicate that people can reflect either adaptively or maladaptively over negative experiences, extant research has not examined how culture influences this process. We compared the self-reflective practices of Russians (members of an interdependent culture characterized by a tendency to brood) and Americans (members of an independent culture in which self-reflection has been studied extensively). We predicted that self-reflection would be associated with less-detrimental outcomes among Russians because they self-distance more when analyzing their feelings than Americans do. Findings from two studies supported these predictions. In Study 1, self-reflection was associated with fewer depressive symptoms among Russians than among Americans. In Study 2, Russians displayed less distress and a more adaptive pattern of construals than Americans after reflecting over a recent negative event. In addition, they self-distanced more than Americans while analyzing their feelings, and self-distancing mediated the cultural differences in self-reflection. These findings demonstrate how culture shapes the way people reflect over negative experiences.

An Adaptive Unified Differential Evolution Algorithm for Global Optimization

Energy Technology Data Exchange (ETDEWEB)

Qiang, Ji; Mitchell, Chad

2014-11-03

In this paper, we propose a new adaptive unified differential evolution algorithm for single-objective global optimization. Instead of the multiple mutation strate- gies proposed in conventional differential evolution algorithms, this algorithm employs a single equation unifying multiple strategies into one expression. It has the virtue of mathematical simplicity and also provides users the flexibility for broader exploration of the space of mutation operators. By making all control parameters in the proposed algorithm self-adaptively evolve during the process of optimization, it frees the application users from the burden of choosing appro- priate control parameters and also improves the performance of the algorithm. In numerical tests using thirteen basic unimodal and multimodal functions, the proposed adaptive unified algorithm shows promising performance in compari- son to several conventional differential evolution algorithms.

Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men: (specific-locus mutations/dose-rate effect/doubling dose/risk estimation)

International Nuclear Information System (INIS)

Russell, W.L.; Kelly, E.M.

1982-01-01

Estimation of the genetic hazards of ionizing radiation in men is based largely on the frequency of transmitted specific-locus mutations induced in mouse spermatogonial stem cells at low radiation dose rates. The publication of new data on this subject has permitted a fresh review of all the information available. The data continue to show no discrepancy from the interpretation that, although mutation frequency decreases markedly as dose rate is decreased from 90 to 0.8 R/min (1 R = 2.6 X 10 -4 coulombs/kg) there seems to be no further change below 0.8 R/min over the range from that dose rate to 0.0007 R/min. Simple mathematical models are used to compute: (a) a maximum likelihood estimate of the induced mutation frequency at the low dose rates, and (b) a maximum likelihood estimate of the ratio of this to the mutation frequency at high dose rates in the range of 72 to 90 R/min. In the application of these results to the estimation of genetic hazards of radiation in man, the former value can be used to calculate a doubling dose - i.e., the dose of radiation that induces a mutation frequency equal to the spontaneous frequency. The doubling dose based on the low-dose-rate data compiled here is 110 R. The ratio of the mutation frequency at low dose rate to that at high dose rate is useful when it becomes necessary to extrapolate from experimental determinations, or from human data, at high dose rates to the expected risk at low dose rates. The ratio derived from the present analysis is 0.33

Performance optimization of PM-16QAM transmission system enabled by real-time self-adaptive coding.

Science.gov (United States)

Qu, Zhen; Li, Yao; Mo, Weiyang; Yang, Mingwei; Zhu, Shengxiang; Kilper, Daniel C; Djordjevic, Ivan B

2017-10-15

We experimentally demonstrate self-adaptive coded 5×100  Gb/s WDM polarization multiplexed 16 quadrature amplitude modulation transmission over a 100 km fiber link, which is enabled by a real-time control plane. The real-time optical signal-to-noise ratio (OSNR) is measured using an optical performance monitoring device. The OSNR measurement is processed and fed back using control plane logic and messaging to the transmitter side for code adaptation, where the binary data are adaptively encoded with three types of low-density parity-check (LDPC) codes with code rates of 0.8, 0.75, and 0.7 of large girth. The total code-adaptation latency is measured to be 2273 ms. Compared with transmission without adaptation, average net capacity improvements of 102%, 36%, and 7.5% are obtained, respectively, by adaptive LDPC coding.

Rate-adaptive BCH codes for distributed source coding

DEFF Research Database (Denmark)

Salmistraro, Matteo; Larsen, Knud J.; Forchhammer, Søren

2013-01-01

This paper considers Bose-Chaudhuri-Hocquenghem (BCH) codes for distributed source coding. A feedback channel is employed to adapt the rate of the code during the decoding process. The focus is on codes with short block lengths for independently coding a binary source X and decoding it given its...... strategies for improving the reliability of the decoded result are analyzed, and methods for estimating the performance are proposed. In the analysis, noiseless feedback and noiseless communication are assumed. Simulation results show that rate-adaptive BCH codes achieve better performance than low...... correlated side information Y. The proposed codes have been analyzed in a high-correlation scenario, where the marginal probability of each symbol, Xi in X, given Y is highly skewed (unbalanced). Rate-adaptive BCH codes are presented and applied to distributed source coding. Adaptive and fixed checking...

Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

KAUST Repository

Patel, Trushar R.; Nikodemus, Denise; Besong, Tabot M.D.; Reuten, Raphael; Meier, Markus; Harding, Stephen E.; Winzor, Donald J.; Koch, Manuel; Stetefeld, Jö rg

2015-01-01

Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function.

Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

KAUST Repository

Patel, Trushar R.

2015-07-26

Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function.

Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum.

Directory of Open Access Journals (Sweden)

Nathaniel P Sharp

2016-03-01

Full Text Available Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.

Assessment of Adaptive Rate Response Provided by Accelerometer, Minute Ventilation and Dual Sensor Compared with Normal Sinus Rhythm During Exercise: A Self-controlled Study in Chronotropically Competent Subjects

Directory of Open Access Journals (Sweden)

Yuanyuan Cao

2015-01-01

Full Text Available Background: Dual sensor (DS for rate adaption was supposed to be more physiological. To evaluate its superiority, the DS (accelerometer [ACC] and minute ventilation [MV] and normal sinus rate response were compared in a self-controlled way during exercise treadmill testing. Methods: This self-controlled study was performed in atrioventricular block patients with normal sinus function who met the indications of pacemaker implant. Twenty-one patients came to the 1-month follow-up visit. Patients performed a treadmill test 1-month post implant while programmed in DDDR and sensor passive mode. For these patients, sensor response factors were left at default settings (ACC = 8, MV = 3 and sensor indicated rates (SIRs for DS, ACC and MV sensor were retrieved from the pacemaker memories, along with measured sinus node (SN rates from the beginning to 1-minute after the end of the treadmill test, and compared among study groups. Repeated measures analysis of variance and profile analysis, as well as variance analysis of randomized block designs, were used for statistical analysis. Results: Fifteen patients (15/21 were determined to be chronotropically competent. The mean differences between DS SIRs and intrinsic sinus rates during treadmill testing were smaller than those for ACC and MV sensor (mean difference between SIR and SN rate: ACC vs. SN, MV vs. SN, DS vs. SN, respectively, 34.84, 17.60, 16.15 beats/min, though no sensors could mimic sinus rates under the default settings for sensor response factor (ACC vs. SN P-adjusted < 0.001; MV vs. SN P-adjusted = 0.002; DS vs. SN P-adjusted = 0.005. However, both in the range of 1 st minute and first 3 minutes of exercise, only the DS SIR profile did not differ from sinus rates (P-adjusted = 0.09, 0.90, respectively. Conclusions: The DS under default settings provides more physiological rate response during physical activity than the corresponding single sensors (ACC or MV sensor. Further study is needed to

Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

Science.gov (United States)

Őri, Zsolt P

2017-05-01

A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

Kalman Filtered Bio Heat Transfer Model Based Self-adaptive Hybrid Magnetic Resonance Thermometry.

Science.gov (United States)

Zhang, Yuxin; Chen, Shuo; Deng, Kexin; Chen, Bingyao; Wei, Xing; Yang, Jiafei; Wang, Shi; Ying, Kui

2017-01-01

To develop a self-adaptive and fast thermometry method by combining the original hybrid magnetic resonance thermometry method and the bio heat transfer equation (BHTE) model. The proposed Kalman filtered Bio Heat Transfer Model Based Self-adaptive Hybrid Magnetic Resonance Thermometry, abbreviated as KalBHT hybrid method, introduced the BHTE model to synthesize a window on the regularization term of the hybrid algorithm, which leads to a self-adaptive regularization both spatially and temporally with change of temperature. Further, to decrease the sensitivity to accuracy of the BHTE model, Kalman filter is utilized to update the window at each iteration time. To investigate the effect of the proposed model, computer heating simulation, phantom microwave heating experiment and dynamic in-vivo model validation of liver and thoracic tumor were conducted in this study. The heating simulation indicates that the KalBHT hybrid algorithm achieves more accurate results without adjusting λ to a proper value in comparison to the hybrid algorithm. The results of the phantom heating experiment illustrate that the proposed model is able to follow temperature changes in the presence of motion and the temperature estimated also shows less noise in the background and surrounding the hot spot. The dynamic in-vivo model validation with heating simulation demonstrates that the proposed model has a higher convergence rate, more robustness to susceptibility problem surrounding the hot spot and more accuracy of temperature estimation. In the healthy liver experiment with heating simulation, the RMSE of the hot spot of the proposed model is reduced to about 50% compared to the RMSE of the original hybrid model and the convergence time becomes only about one fifth of the hybrid model. The proposed model is able to improve the accuracy of the original hybrid algorithm and accelerate the convergence rate of MR temperature estimation.

A neural learning classifier system with self-adaptive constructivism for mobile robot control.

Science.gov (United States)

Hurst, Jacob; Bull, Larry

2006-01-01

For artificial entities to achieve true autonomy and display complex lifelike behavior, they will need to exploit appropriate adaptable learning algorithms. In this context adaptability implies flexibility guided by the environment at any given time and an open-ended ability to learn appropriate behaviors. This article examines the use of constructivism-inspired mechanisms within a neural learning classifier system architecture that exploits parameter self-adaptation as an approach to realize such behavior. The system uses a rule structure in which each rule is represented by an artificial neural network. It is shown that appropriate internal rule complexity emerges during learning at a rate controlled by the learner and that the structure indicates underlying features of the task. Results are presented in simulated mazes before moving to a mobile robot platform.

Reliability of self-reported diagnostic radiation history in BRCA1/2 mutation carriers

International Nuclear Information System (INIS)

Pijpe, Anouk; Manders, Peggy; Mulder, Renee L.; Leeuwen, Flora E. van; Rookus, Matti A.

2010-01-01

We assessed reliability of self-reported diagnostic radiation history in BRCA1/2 mutation carriers with and without breast cancer. Within the frame-work of the HEBON study, 401 BRCA1/2 mutation carriers completed a baseline (1999-2004) and a follow-up questionnaire (2006-2007). Test-retest reliability of self-reported exposure to chest X-rays, fluoroscopies and mammograms was assessed for the entire study population and by case status. Overall proportion agreement on reporting ever/never exposure was good (> 75%), while the corresponding kappa coefficients were between 0.40 and 0.75, indicating at least moderate reliability beyond chance. Reliability of number of exposures was also good (> 75%). Proportion agreement on reporting age at first mammogram was low (40%) for exact consistency and moderate (60%) for consistency ± 1 year. Reliability of age at first mammogram was higher for cases than for unaffected carriers (P < 0.001) but this difference disappeared when excluding diagnostic mammograms (P = 0.60). In unaffected carriers proportion agreement on age at last mammogram was 50%. In general, the direction of disagreement on all items was equally distributed. More consistent reporting was mainly determined by a younger age at questionnaire completion. In conclusion, inconsistent self-report of diagnostic radiation by BRCA1/2 mutation carriers was mainly non-differential by disease status.

Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals.

Science.gov (United States)

Link, Vivian; Aguilar-Gómez, Diana; Ramírez-Suástegui, Ciro; Hurst, Laurence D; Cortez, Diego

2017-09-01

In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Male mutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12-3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain >68% of these variations in monotremes, and in control species, rodents, and primates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Y-chromosome-specific microsatellite mutation rates re-examined using a minisatellite, MSY1.

Science.gov (United States)

Jobling, M A; Heyer, E; Dieltjes, P; de Knijff, P

1999-10-01

Polymorphic Y-chromosome-specific microsatellites are becoming increasingly used in evolutionary and forensic studies and, in particular, in dating the origins of Y-chromosomal lineages. Previously, haplotyping of Y chromosomes from males belonging to a set of deep-rooting pedigrees was used to estimate a conservative average Y-chromosomal microsatellite mutation rate of 2.1 x 10(-3)per locus per generation. A number of males showed multiple differences in haplotypes compared with other males within their pedigrees, and these were excluded from the calculation of this estimate, on the grounds that non-paternity was a more probable explanation than multiple mutation within a lineage. Here we reanalyse the pedigrees using an independent highly polymorphic system, the Y-specific minisatellite, MSY1. This supports the hypothesis of non-paternity where more than one microsatellite difference was observed, provides further support for the previously deduced microsatellite mutation rate and throws light on the mutation dynamics of MSY1 itself, suggesting that single-step changes are not the only mode of mutation.

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

Directory of Open Access Journals (Sweden)

Arbel Harpak

2016-12-01

Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

Towards Self-adaptation for Dependable Service-Oriented Systems

Science.gov (United States)

Cardellini, Valeria; Casalicchio, Emiliano; Grassi, Vincenzo; Lo Presti, Francesco; Mirandola, Raffaela

Increasingly complex information systems operating in dynamic environments ask for management policies able to deal intelligently and autonomously with problems and tasks. An attempt to deal with these aspects can be found in the Service-Oriented Architecture (SOA) paradigm that foresees the creation of business applications from independently developed services, where services and applications build up complex dependencies. Therefore the dependability of SOA systems strongly depends on their ability to self-manage and adapt themselves to cope with changes in the operating conditions and to meet the required dependability with a minimum of resources. In this paper we propose a model-based approach to the realization of self-adaptable SOA systems, aimed at the fulfillment of dependability requirements. Specifically, we provide a methodology driving the system adaptation and we discuss the architectural issues related to its implementation. To bring this approach to fruition, we developed a prototype tool and we show the results that can be achieved with a simple example.

Adapting to rates versus amounts of climate change: a case of adaptation to sea-level rise

Science.gov (United States)

Shayegh, Soheil; Moreno-Cruz, Juan; Caldeira, Ken

2016-10-01

Adaptation is the process of adjusting to climate change in order to moderate harm or exploit beneficial opportunities associated with it. Most adaptation strategies are designed to adjust to a new climate state. However, despite our best efforts to curtail greenhouse gas emissions, climate is likely to continue changing far into the future. Here, we show how considering rates of change affects the projected optimal adaptation strategy. We ground our discussion with an example of optimal investment in the face of continued sea-level rise, presenting a quantitative model that illustrates the interplay among physical and economic factors governing coastal development decisions such as rate of sea-level rise, land slope, discount rate, and depreciation rate. This model shows that the determination of optimal investment strategies depends on taking into account future rates of sea-level rise, as well as social and political constraints. This general approach also applies to the development of improved strategies to adapt to ongoing trends in temperature, precipitation, and other climate variables. Adaptation to some amount of change instead of adaptation to ongoing rates of change may produce inaccurate estimates of damages to the social systems and their ability to respond to external pressures.

Adaptive control for a PWR using a self-tuning reference model concept

International Nuclear Information System (INIS)

Miley, G.H.; Park, G.T.; Kim, B.S.

1992-01-01

Possible applications of an adaptive control method to a pressurized-water reactor nuclear power plant are investigated. The self-tuning technique with a reference model concept is employed. This control algorithm is developed by combining the self-tuning controller with the model reference adaptive control. This approach overcomes the difficulties in choosing the appropriate weighting polynomials in the cost function of the self-tuning control

Beamspace Adaptive Beamforming for Hydrodynamic Towed Array Self-Noise Cancellation

National Research Council Canada - National Science Library

Premus, Vincent

2001-01-01

... against signal self-nulling associated with steering vector mismatch. Particular attention is paid to the definition of white noise gain as the metric that reflects the level of mainlobe adaptive nulling for an adaptive beamformer...

Beamspace Adaptive Beamforming for Hydrodynamic Towed Array Self-Noise Cancellation

National Research Council Canada - National Science Library

Premus, Vincent

2000-01-01

... against signal self-nulling associated with steering vector mismatch. Particular attention is paid to the definition of white noise gain as the metric that reflects the level of mainlobe adaptive nulling for an adaptive beamformer...

Translation and cross-cultural adaptation of the Rating Scale for Countertransference (RSCT to American English

Directory of Open Access Journals (Sweden)

Rafael Mondrzak

Full Text Available Abstract Introduction: The Rating Scale for Countertransference (RSCT - originally, Escala para Avaliação de Contratransferência (EACT - is a self-administered instrument comprising questions that assess 23 feelings (divided into three blocs, closeness, distance, and indifference that access conscious countertransferential emotions and sentiments. This paper describes the process of translation and cross-cultural adaptation of the RSCT into American English. Methods: This study employed the guidelines proposed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR Task Force for Translation and Cultural Adaptation which define 10 steps for translation and cross-cultural adaptation of self-report instruments. Additionally, semantic equivalence tools were employed to select the final versions of terms used. The author of the RSCT gave permission for translation and took part in the process. The instrument is available for use free of charge. Results: Analysis of the back-translation showed that just seven of the 23 terms needed to be adjusted to arrive at the final version in American English. Conclusions: This study applied rigorous standards to construct a version of the RSCT in American English. This version of the RSCT translated and adapted into American English should be of great use for accessing and researching countertransferential feelings that are part of psychodynamic treatment.

Prospects for DNA methods to measure human heritable mutation rates

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1985-01-01

A workshop cosponsored by ICPEMC and the US Department of Energy was held in Alta, Utah, December 9-13, 1984 to examine the extent to which DNA-oriented methods might provide new approaches to the important but intractable problem of measuring mutation rates in control and exposed human populations. The workshop identified and analyzed six DNA methods for detection of human heritable mutation, including several created at the meeting, and concluded that none of the methods combine sufficient feasibility and efficiency to be recommended for general application. 8 refs

Self-adapted thermocouple-diagnostic complex

International Nuclear Information System (INIS)

Alekseev, S.V.; Grankovskij, K.Eh.; Olejnikov, P.P.; Prijmak, S.V.; Shikalov, V.F.

2003-01-01

A self-adapted thermocouple-diagnostic complex (STDC) for obtaining the reliable data on the coolant temperature in the reactors of NPP is described. The STDC in based on the thermal pulse monitoring of a thermocouple in the measuring channel of a reactor. Measurement method and STDC composition are substantiated. It is shown that introduction of the developed STDC ensures realization of precise and reliable temperature monitoring in the reactors of all types [ru

Change in self-rated general health is associated with perceived illness burden

DEFF Research Database (Denmark)

Nielsen, Anni Brit Sternhagen; Jensen, Per; Gannik, Dorte Effersøe

2015-01-01

Background: iabetic patients’ lifestyle adaptations to improve glycaemic control are not always followed by improvements in self-rated general health (SRH). The perceived impact of diabetes on patients’ daily lives may influence changes in their SRH. This paper examines the association of illness...... diabetes-related symptoms, and cardiovascular disease were related to lower SRH ratings. On average SRH improved by 0.46 (95% CI: 0.37; 0.55) during the first year after diagnosis without inclusion of covariates. Mental and practical illness burden was the only factor associated with change in SRH...

Self-rated health and age

DEFF Research Database (Denmark)

Andersen, Frank Krarup; Christensen, Kaare; Frederiksen, Henrik

2007-01-01

AIMS: The aim of this study was to explore and describe self-rated health in middle-aged and elderly Danes using both a cross-sectional and a longitudinal design. Global and (age) comparative self-rated health are examined and compared. METHODS: This study is interview based and comprises data on...

Increase of the spontaneous mutation rate in a long-term experiment with Drosophila melanogaster.

Science.gov (United States)

Avila, Victoria; Chavarrías, David; Sánchez, Enrique; Manrique, Antonio; López-Fanjul, Carlos; García-Dorado, Aurora

2006-05-01

In a previous experiment, the effect of 255 generations of mutation accumulation (MA) on the second chromosome viability of Drosophila melanogaster was studied using 200 full-sib MA1 lines and a large C1 control, both derived from a genetically homogeneous base population. At generation 265, one of those MA1 lines was expanded to start 150 new full-sib MA2 lines and a new C2 large control. After 46 generations, the rate of decline in mean viability in MA2 was approximately 2.5 times that estimated in MA1, while the average degree of dominance of mutations was small and nonsignificant by generation 40 and moderate by generation 80. In parallel, the inbreeding depression rate for viability and the amount of additive variance for two bristle traits in C2 were 2-3 times larger than those in C1. The results are consistent with a mutation rate in the line from which MA2 and C2 were derived about 2.5 times larger than that in MA1. The mean viability of C2 remained roughly similar to that of C1, but the rate of MA2 line extinction increased progressively, leading to mutational collapse, which can be ascribed to accelerated mutation and/or synergy after important deleterious accumulation.

Correlation between self-differentiation and professional adaptability among undergraduate nursing students in China

Directory of Open Access Journals (Sweden)

Si-wei Liu

2016-12-01

Conclusion: The level of self-differentiation of undergraduate nursing studentsaffects their professional adaptability. Nursing educators should consider the characteristics of self-differentiation of undergraduate nursing students in developing measures to improve their professional adaptability.

Does self-employment really raise job satisfaction? Adaptation and anticipation effects on self-employment and general job changes

OpenAIRE

Hanglberger, Dominik; Merz, Joachim

2015-01-01

Empirical analyses using cross-sectional and panel data found significantly higher levels of job satisfaction for the self-employed than for employees. We argue that by neglecting anticipation and adaptation effects estimates in previous studies might be misleading. To test this, we specify models accounting for anticipation and adaptation to self-employment and general job changes. In contrast to recent literature we find no specific long-term effect of self-employment on job satisfaction. A...

Executive functioning independently predicts self-rated health and improvement in self-rated health over time among community-dwelling older adults.

Science.gov (United States)

McHugh, Joanna Edel; Lawlor, Brian A

2016-01-01

Self-rated health, as distinct from objective measures of health, is a clinically informative metric among older adults. The purpose of our study was to examine the cognitive and psychosocial factors associated with self-rated health. 624 participants over the age of 60 were assessed at baseline, and of these, 510 were contacted for a follow-up two years later. Measures of executive function and self-rated health were assessed at baseline, and self-rated health was assessed at follow-up. We employed multiple linear regression analyses to investigate the relationship between executive functioning and self-rated health, while controlling for demographic, psychosocial and biological variables. Controlling for other relevant variables, executive functioning independently and solely predicted self-rated health, both at a cross-sectional level, and also over time. Loneliness was also found to cross-sectionally predict self-rated health, although this relationship was not present at a longitudinal level. Older adults' self-rated health may be related to their executive functioning and to their loneliness. Self-rated health appeared to improve over time, and the extent of this improvement was also related to executive functioning at baseline. Self-rated health may be a judgement made of one's functioning, especially executive functioning, which changes with age and therefore may be particularly salient in the reflections of older adults.

Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

Science.gov (United States)

Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

2017-12-01

This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong

A Novel Self-Adaptive Harmony Search Algorithm

Directory of Open Access Journals (Sweden)

Kaiping Luo

2013-01-01

Full Text Available The harmony search algorithm is a music-inspired optimization technology and has been successfully applied to diverse scientific and engineering problems. However, like other metaheuristic algorithms, it still faces two difficulties: parameter setting and finding the optimal balance between diversity and intensity in searching. This paper proposes a novel, self-adaptive search mechanism for optimization problems with continuous variables. This new variant can automatically configure the evolutionary parameters in accordance with problem characteristics, such as the scale and the boundaries, and dynamically select evolutionary strategies in accordance with its search performance. The new variant simplifies the parameter setting and efficiently solves all types of optimization problems with continuous variables. Statistical test results show that this variant is considerably robust and outperforms the original harmony search (HS, improved harmony search (IHS, and other self-adaptive variants for large-scale optimization problems and constrained problems.

mHealth intervention to support asthma self-management in adolescents: the ADAPT study.

Science.gov (United States)

Kosse, Richelle C; Bouvy, Marcel L; de Vries, Tjalling W; Kaptein, Ad A; Geers, Harm Cj; van Dijk, Liset; Koster, Ellen S

2017-01-01

Poor medication adherence in adolescents with asthma results in poorly controlled disease and increased morbidity. The aim of the ADolescent Adherence Patient Tool (ADAPT) study is to develop an mHealth intervention to support self-management and to evaluate the effectiveness in improving medication adherence and asthma control. The ADAPT intervention consists of an interactive smartphone application (app) connected to a desktop application for health care providers, in this study, the community pharmacist. The app contains several functions to improve adherence as follows: 1) a questionnaire function to rate asthma symptoms and monitor these over time; 2) short movie clips with medication and disease information; 3) a medication reminder; 4) a chat function with peers; and 5) a chat function with the pharmacist. The pharmacist receives data from the patient's app through the desktop application, which enables the pharmacist to send information and feedback to the patient. The ADAPT intervention is tested in a community pharmacy-based cluster randomized controlled trial in the Netherlands, aiming to include 352 adolescents with asthma. The main outcome is adherence, measured by patient's self-report and refill adherence calculated from pharmacy dispensing records. In addition, asthma control, illness perceptions, medication beliefs, and asthma-related quality of life are measured. This study will provide in-depth knowledge on the effectiveness of an mHealth intervention to support asthma self-management in adolescents. These insights will also be useful for adolescents with other chronic diseases.

Evolution of Escherichia coli to 42 °C and Subsequent Genetic Engineering Reveals Adaptive Mechanisms and Novel Mutations

DEFF Research Database (Denmark)

Sandberg, Troy E.; Pedersen, Margit; LaCroix, Ryan A.

2014-01-01

Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation to a desired environment. Here, we performed ALE to 42 °C of ten parallel populations of Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental c...... targets for additional ameliorating mutations. Overall, the results of this study provide insight into the adaptation process and yield lessons important for the future implementation of ALE as a tool for scientific research and engineering....

Sex speeds adaptation by altering the dynamics of molecular evolution.

Science.gov (United States)

McDonald, Michael J; Rice, Daniel P; Desai, Michael M

2016-03-10

Sex and recombination are pervasive throughout nature despite their substantial costs. Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology. One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation. Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect) or by separating them from deleterious load (the ruby in the rubbish effect). Previous experiments confirm that sex can increase the rate of adaptation, but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.

A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data.

Science.gov (United States)

Bertl, Johanna; Guo, Qianyun; Juul, Malene; Besenbacher, Søren; Nielsen, Morten Muhlig; Hornshøj, Henrik; Pedersen, Jakob Skou; Hobolth, Asger

2018-04-19

Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration. To take into account the fine scale of the explanatory variables, we model the probabilities of different types of mutations for each position in the genome by multinomial logistic regression. We analyse 505 cancer genomes from 14 different cancer types and compare the performance in predicting mutation rate for both regional based models and site-specific models. We show that for 1000 randomly selected genomic positions, the site-specific model predicts the mutation rate much better than regional based models. We use a forward selection procedure to identify the most important explanatory variables. The procedure identifies site-specific conservation (phyloP), replication timing, and expression level as the best predictors for the mutation rate. Finally, our model confirms and quantifies certain well-known mutational signatures. We find that our site-specific multinomial regression model outperforms the regional based models. The possibility of including genomic variables on different scales and patient specific variables makes it a versatile framework for studying different mutational mechanisms. Our model can serve as the neutral null model

Genome-Wide Mutation Rate Response to pH Change in the Coral Reef Pathogen Vibrio shilonii AK1.

Science.gov (United States)

Strauss, Chloe; Long, Hongan; Patterson, Caitlyn E; Te, Ronald; Lynch, Michael

2017-08-22

Recent application of mutation accumulation techniques combined with whole-genome sequencing (MA/WGS) has greatly promoted studies of spontaneous mutation. However, such explorations have rarely been conducted on marine organisms, and it is unclear how marine habitats have influenced genome stability. This report resolves the mutation rate and spectrum of the coral reef pathogen Vibrio shilonii , which causes coral bleaching and endangers the biodiversity maintained by coral reefs. We found that its mutation rate and spectrum are highly similar to those of other studied bacteria from various habitats, despite the saline environment. The mutational properties of this marine bacterium are thus controlled by other general evolutionary forces such as natural selection and genetic drift. We also found that as pH drops, the mutation rate decreases and the mutation spectrum is biased in the direction of generating G/C nucleotides. This implies that evolutionary features of this organism and perhaps other marine microbes might be altered by the increasingly acidic ocean water caused by excess CO 2 emission. Nonetheless, further exploration is needed as the pH range tested in this study was rather narrow and many other possible mutation determinants, such as carbonate increase, are associated with ocean acidification. IMPORTANCE This study explored the pH dependence of a bacterial genome-wide mutation rate. We discovered that the genome-wide rates of appearance of most mutation types decrease linearly and that the mutation spectrum is biased in generating more G/C nucleotides with pH drop in the coral reef pathogen V. shilonii . Copyright © 2017 Strauss et al.

An approximate stationary solution for multi-allele neutral diffusion with low mutation rates.

Science.gov (United States)

Burden, Conrad J; Tang, Yurong

2016-12-01

We address the problem of determining the stationary distribution of the multi-allelic, neutral-evolution Wright-Fisher model in the diffusion limit. A full solution to this problem for an arbitrary K×K mutation rate matrix involves solving for the stationary solution of a forward Kolmogorov equation over a (K-1)-dimensional simplex, and remains intractable. In most practical situations mutations rates are slow on the scale of the diffusion limit and the solution is heavily concentrated on the corners and edges of the simplex. In this paper we present a practical approximate solution for slow mutation rates in the form of a set of line densities along the edges of the simplex. The method of solution relies on parameterising the general non-reversible rate matrix as the sum of a reversible part and a set of (K-1)(K-2)/2 independent terms corresponding to fluxes of probability along closed paths around faces of the simplex. The solution is potentially a first step in estimating non-reversible evolutionary rate matrices from observed allele frequency spectra. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae

NARCIS (Netherlands)

Zeyl, C.; Visser, de J.A.G.M.

2001-01-01

The per-genome, per-generation rate of spontaneous mutation affecting fitness (U) and the mean fitness cost per mutation (s) are important parameters in evolutionary genetics, but have been estimated for few species. We estimated U and sh (the heterozygous effect of mutations) for two diploid yeast

The effects of MSH2 deficiency on spontaneous and radiation-induced mutation rates in the mouse germline

International Nuclear Information System (INIS)

Burr, Karen L-A.; Duyn-Goedhart, Annemarie van; Hickenbotham, Peter; Monger, Karen; Buul, Paul P.W. van; Dubrova, Yuri E.

2007-01-01

Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of mismatch repair deficient Msh2 knock-out mice. Spontaneous mutation rates in homozygous Msh2 -/- males were significantly higher than those in isogenic wild-type (Msh2 +/+ ) and heterozygous (Msh2 +/- ) mice. In contrast, the irradiated Msh2 -/- mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated Msh2 +/+ and Msh2 +/- animals. Considering these data and the results of other publications, we propose that the Msh2-deficient mice possess a mutator phenotype in their germline and somatic tissues while the loss of a single Msh2 allele does not affect the stability of heterozygotes

Quantitative evaluation of DNA damage and mutation rate by atmospheric and room-temperature plasma (ARTP) and conventional mutagenesis.

Science.gov (United States)

Zhang, Xue; Zhang, Chong; Zhou, Qian-Qian; Zhang, Xiao-Fei; Wang, Li-Yan; Chang, Hai-Bo; Li, He-Ping; Oda, Yoshimitsu; Xing, Xin-Hui

2015-07-01

DNA damage is the dominant source of mutation, which is the driving force of evolution. Therefore, it is important to quantitatively analyze the DNA damage caused by different mutagenesis methods, the subsequent mutation rates, and their relationship. Atmospheric and room temperature plasma (ARTP) mutagenesis has been used for the mutation breeding of more than 40 microorganisms. However, ARTP mutagenesis has not been quantitatively compared with conventional mutation methods. In this study, the umu test using a flow-cytometric analysis was developed to quantify the DNA damage in individual viable cells using Salmonella typhimurium NM2009 as the model strain and to determine the mutation rate. The newly developed method was used to evaluate four different mutagenesis systems: a new ARTP tool, ultraviolet radiation, 4-nitroquinoline-1-oxide (4-NQO), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutagenesis. The mutation rate was proportional to the corresponding SOS response induced by DNA damage. ARTP caused greater DNA damage to individual living cells than the other conventional mutagenesis methods, and the mutation rate was also higher. By quantitatively comparing the DNA damage and consequent mutation rate after different types of mutagenesis, we have shown that ARTP is a potentially powerful mutagenesis tool with which to improve the characteristics of microbial cell factories.

Divergence times in Caenorhabditis and Drosophila inferred from direct estimates of the neutral mutation rate.

Science.gov (United States)

Cutter, Asher D

2008-04-01

Accurate inference of the dates of common ancestry among species forms a central problem in understanding the evolutionary history of organisms. Molecular estimates of divergence time rely on the molecular evolutionary prediction that neutral mutations and substitutions occur at the same constant rate in genomes of related species. This underlies the notion of a molecular clock. Most implementations of this idea depend on paleontological calibration to infer dates of common ancestry, but taxa with poor fossil records must rely on external, potentially inappropriate, calibration with distantly related species. The classic biological models Caenorhabditis and Drosophila are examples of such problem taxa. Here, I illustrate internal calibration in these groups with direct estimates of the mutation rate from contemporary populations that are corrected for interfering effects of selection on the assumption of neutrality of substitutions. Divergence times are inferred among 6 species each of Caenorhabditis and Drosophila, based on thousands of orthologous groups of genes. I propose that the 2 closest known species of Caenorhabditis shared a common ancestor <24 MYA (Caenorhabditis briggsae and Caenorhabditis sp. 5) and that Caenorhabditis elegans diverged from its closest known relatives <30 MYA, assuming that these species pass through at least 6 generations per year; these estimates are much more recent than reported previously with molecular clock calibrations from non-nematode phyla. Dates inferred for the common ancestor of Drosophila melanogaster and Drosophila simulans are roughly concordant with previous studies. These revised dates have important implications for rates of genome evolution and the origin of self-fertilization in Caenorhabditis.

Relationship between adaptation and self-esteem in addicted female prisoners in the south east of Iran.

Science.gov (United States)

Torkaman, Mahya; Miri, Sakineh; Farokhzadian, Jamileh

2018-02-12

Background Reduction of the adaptation and self-esteem can be the consequence of opium addiction and imprisonment. Drug use causes inappropriate behaviors in women, which are quite different from those in men. Social deviations, prostitution, high-risk sexual behaviors, abortion, divorce and imprisonment followed by loss of self-esteem are the consequences of women's addiction. The present study was conducted to assess the relationship between adaptation and self-esteem in addicted female prisoners. Methods In this descriptive analytical study, 130 addicted female prisoners were selected from a prison in the south east of Iran using census sampling. The data were collected by a demographic questionnaire, the Rosenberg's self-esteem scale and the bell adjustment inventory (BAI). Results According to the results, women's adaptation fell into the 'very unsatisfactory' range. The highest mean was related to the emotional dimension, while the lowest mean was in terms of the health dimension. In total, 96.4% of the participating women had low adaptation. The mean total self-esteem fell into the low range; in fact, 84.6% of the women had a low self-esteem. The results showed no significant relationships between adaptation and self-esteem in these women; however, self-esteem was significantly and inversely related to health and emotional adaptation. Conclusion The findings showed that the majority of the women had unsatisfactory adaptation as well as poor self-esteem. No significant relationships were observed between adaptation and self-esteem in the addicted female prisoners.

Microsatellite frequencies vary with body mass and body temperature in mammals, suggesting correlated variation in mutation rate

Directory of Open Access Journals (Sweden)

William Amos

2014-11-01

Full Text Available Substitution rate is often found to correlate with life history traits such as body mass, a predictor of population size and longevity, and body temperature. The underlying mechanism is unclear but most models invoke either natural selection or factors such as generation length that change the number of mutation opportunities per unit time. Here we use published genome sequences from 69 mammals to ask whether life history traits impact another form of genetic mutation, the high rates of predominantly neutral slippage in microsatellites. We find that the length-frequency distributions of three common dinucleotide motifs differ greatly between even closely related species. These frequency differences correlate with body mass and body temperature and can be used to predict the phenotype of an unknown species. Importantly, different length microsatellites show complicated patterns of excess and deficit that cannot be explained by a simple model where species with short generation lengths have experienced more mutations. Instead, the patterns probably require changes in mutation rate that impact alleles of different length to different extents. Body temperature plausibly influences mutation rate by modulating the propensity for slippage. Existing hypotheses struggle to account for a link between body mass and mutation rate. However, body mass correlates inversely with population size, which in turn predicts heterozygosity. We suggest that heterozygote instability, HI, the idea that heterozygous sites show increased mutability, could provide a plausible link between body mass and mutation rate.

The role of disability self-concept in adaptation to congenital or acquired disability.

Science.gov (United States)

Bogart, Kathleen R

2014-02-01

Current theories of adaptation to disability do not address differences in adaptation to congenital or acquired disability. Although people with congenital disabilities are generally assumed to be better adapted than people with acquired disabilities, few studies have tested this, and even fewer have attempted to explain the mechanisms behind these differences. This study tested the proposition that whether a disability is congenital or acquired plays an important role in the development of the disability self-concept (consisting of disability identity and disability self-efficacy), which in turn, affects satisfaction with life. It was predicted that disability self-concept would be better developed among people with congenital, compared with acquired disabilities, predicting greater satisfaction with life in those with acquired conditions. 226 participants with congenital and acquired mobility disabilities completed a cross-sectional online questionnaire measuring satisfaction with life, self-esteem, disability identity, disability self-efficacy, and demographic information. Self-esteem, disability identity, disability self-efficacy, and income were significant predictors of satisfaction with life. Congenital onset predicted higher satisfaction with life; disability identity and disability self-efficacy, but not self-esteem, partially mediated the relationship. Findings highlight the distinction between adaptation to congenital versus acquired disability and the importance of disability self-concept, which are underresearched constructs. Results suggest that rather than attempting to "normalize" individuals with disabilities, health care professionals should foster their disability self-concept. Possible ways to improve disability self-concept are discussed, such as involvement in the disability community and disability pride. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Interfering Waves of Adaptation Promote Spatial Mixing

DEFF Research Database (Denmark)

Martens, Erik Andreas; Hallatschek, Oskar

2011-01-01

A fundamental problem of asexual adaptation is that beneficial substitutions are not efficiently accumulated in large populations: Beneficial mutations often go extinct because they compete with one another in going to fixation. It has been argued that such clonal interference may have led...... to the evolution of sex and recombination in well-mixed populations. Here, we study clonal interference, and mechanisms of its mitigation, in an evolutionary model of spatially structured populations with uniform selection pressure. Clonal interference is much more prevalent with spatial structure than without......, due to the slow wave-like spread of beneficial mutations through space. We find that the adaptation speed of asexuals saturates when the linear habitat size exceeds a characteristic interference length, which becomes shorter with smaller migration and larger mutation rate. The limiting speed...

Engaging a moving target: Adapting to rates of climate change

Science.gov (United States)

Shayegh, S.; Caldeira, K.; Moreno-Cruz, J.

2015-12-01

Climate change is affecting the planet and its human and natural systems at an increasing rate. As temperatures continue to rise, the international community has increasingly been considering adaptation measures to prepare for future climate change. However, most discussion around adaptation strategies has focused on preparedness for some expected amount of climate change impacts, e.g. 2 meters sea level rise. In this study, we discuss adaptation to rates of change as an alternative conceptual framework for thinking about adaptation. Adaptation is not only about adapting to amounts of change, but the rate at which these changes occur is also critically important. We ground our discussion with an example of optimal coastal investment in the face of ongoing sea level rise. Sea level rise threatens coastal assets. Finite resources could be devoted to building infrastructure further inland or to building coastal defense systems. A possible policy response could be to create a "no-build" coastal buffer zone that anticipates a future higher sea level. We present a quantitative model that illustrates the interplay among various important factors (rate of sea level rise, discount rate, capital depreciation rate, attractiveness of coastal land, etc). For some cases, strategies that combine periodic defensive investments (e.g. dikes) with planned retreat can maximize welfare when adapting to rates of climate change. In other cases, planned retreat may be optimal. It is important to prepare for ongoing increasing amounts of climate change. Preparing for a fixed amount of climate change can lead to a suboptimal solution. Climate is likely to continue changing throughout this century and beyond. To reduce adverse climate impacts, ecosystems and human systems will need to continuously adapt to a moving target.

Parameters identification of photovoltaic models using self-adaptive teaching-learning-based optimization

International Nuclear Information System (INIS)

Yu, Kunjie; Chen, Xu; Wang, Xin; Wang, Zhenlei

2017-01-01

Highlights: • SATLBO is proposed to identify the PV model parameters efficiently. • In SATLBO, the learners self-adaptively select different learning phases. • An elite learning is developed in teacher phase to perform local searching. • A diversity learning is proposed in learner phase to maintain population diversity. • SATLBO achieves the first in ranking on overall performance among nine algorithms. - Abstract: Parameters identification of photovoltaic (PV) model based on measured current-voltage characteristic curves plays an important role in the simulation and evaluation of PV systems. To accurately and reliably identify the PV model parameters, a self-adaptive teaching-learning-based optimization (SATLBO) is proposed in this paper. In SATLBO, the learners can self-adaptively select different learning phases based on their knowledge level. The better learners are more likely to choose the learner phase for improving the population diversity, while the worse learners tend to choose the teacher phase to enhance the convergence rate. Thus, learners at different levels focus on different searching abilities to efficiently enhance the performance of algorithm. In addition, to improve the searching ability of different learning phases, an elite learning strategy and a diversity learning method are introduced into the teacher phase and learner phase, respectively. The performance of SATLBO is firstly evaluated on 34 benchmark functions, and experimental results show that SATLBO achieves the first in ranking on the overall performance among nine algorithms. Then, SATLBO is employed to identify parameters of different PV models, i.e., single diode, double diode, and PV module. Experimental results indicate that SATLBO exhibits high accuracy and reliability compared with other parameter extraction methods.

Determinants of self-rated health of Warsaw inhabitants.

Science.gov (United States)

Supranowicz, Piotr; Wysocki, Mirosław J; Car, Justyna; Debska, Anna; Gebska-Kuczerowska, Anita

2012-01-01

Self-rated health is a one-point measure commonly used for recognising subjectively perceived health and covering a wide range of individual's health aspects. The aim of our study was to examine the extent to which self-rated health reflects the differences due to demographic characteristics, physical, psychical and social well-being, health disorders, occurrence of chronic disease and negative life events in Polish social and cultural conditions. Data were collected by non-addressed questionnaire methods from 402 Warsaw inhabitants. The questionnaire contained the questions concerning self-rated health, physical, psychical and social well-being, the use of health care services, occurrence of chronic disease and contact with negative life events. The analysis showed that worse self-rated health increased exponentially with age and less sharply with lower level of education. Pensioners were more likely to assess their own health worse then employed or students. Such difference was not found for unemployed. Compared to married, the self-rated health of divorced or widowed respondents was lower. Gender does not differentiate self-rated health. In regard to well-being, self-rated health linearly decreased for physical well-being, for social and, especially, for psychical well-being the differences were significant, but more complicated. Hospitalisation, especially repeated, strongly determined worse self-rated health. In contrast, relationship between self-rated health and sickness absence or frequency of contact with physician were lower. Chronic diseases substantially increased the risk of poorer self-rated health, and their co-morbidity increased the risk exponentially. The patients with cancer were the group, in which the risk several times exceeded that reported for the patients of other diseases. Regarding negative life events, only experience with violence and financial difficulties were resulted in worse self-rated health. Our findings confirmed the usefulness

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.

Fast maximum likelihood estimation of mutation rates using a birth-death process.

Science.gov (United States)

Wu, Xiaowei; Zhu, Hongxiao

2015-02-07

Since fluctuation analysis was first introduced by Luria and Delbrück in 1943, it has been widely used to make inference about spontaneous mutation rates in cultured cells. Under certain model assumptions, the probability distribution of the number of mutants that appear in a fluctuation experiment can be derived explicitly, which provides the basis of mutation rate estimation. It has been shown that, among various existing estimators, the maximum likelihood estimator usually demonstrates some desirable properties such as consistency and lower mean squared error. However, its application in real experimental data is often hindered by slow computation of likelihood due to the recursive form of the mutant-count distribution. We propose a fast maximum likelihood estimator of mutation rates, MLE-BD, based on a birth-death process model with non-differential growth assumption. Simulation studies demonstrate that, compared with the conventional maximum likelihood estimator derived from the Luria-Delbrück distribution, MLE-BD achieves substantial improvement on computational speed and is applicable to arbitrarily large number of mutants. In addition, it still retains good accuracy on point estimation. Published by Elsevier Ltd.

Reduced Mutation Rate and Increased Transformability of Transposon-Free Acinetobacter baylyi ADP1-ISx.

Science.gov (United States)

Suárez, Gabriel A; Renda, Brian A; Dasgupta, Aurko; Barrick, Jeffrey E

2017-09-01

The genomes of most bacteria contain mobile DNA elements that can contribute to undesirable genetic instability in engineered cells. In particular, transposable insertion sequence (IS) elements can rapidly inactivate genes that are important for a designed function. We deleted all six copies of IS 1236 from the genome of the naturally transformable bacterium Acinetobacter baylyi ADP1. The natural competence of ADP1 made it possible to rapidly repair deleterious point mutations that arose during strain construction. In the resulting ADP1-ISx strain, the rates of mutations inactivating a reporter gene were reduced by 7- to 21-fold. This reduction was higher than expected from the incidence of new IS 1236 insertions found during a 300-day mutation accumulation experiment with wild-type ADP1 that was used to estimate spontaneous mutation rates in the strain. The extra improvement appears to be due in part to eliminating large deletions caused by IS 1236 activity, as the point mutation rate was unchanged in ADP1-ISx. Deletion of an error-prone polymerase ( dinP ) and a DNA damage response regulator ( umuD Ab [the umuD gene of A. baylyi ]) from the ADP1-ISx genome did not further reduce mutation rates. Surprisingly, ADP1-ISx exhibited increased transformability. This improvement may be due to less autolysis and aggregation of the engineered cells than of the wild type. Thus, deleting IS elements from the ADP1 genome led to a greater than expected increase in evolutionary reliability and unexpectedly enhanced other key strain properties, as has been observed for other clean-genome bacterial strains. ADP1-ISx is an improved chassis for metabolic engineering and other applications. IMPORTANCE Acinetobacter baylyi ADP1 has been proposed as a next-generation bacterial host for synthetic biology and genome engineering due to its ability to efficiently take up DNA from its environment during normal growth. We deleted transposable elements that are capable of copying themselves

Population carrier rates of pathogenic ARSA gene mutations: is metachromatic leukodystrophy underdiagnosed?

Directory of Open Access Journals (Sweden)

Agnieszka Ługowska

Full Text Available BACKGROUND: Metachromatic leukodystrophy (MLD is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100,000 live births varied from 0.6 to 2.5. Our purpose was to estimate the birth prevalence of MLD in Poland by determining population frequency of the common pathogenic ARSA gene mutations and to compare this estimate with epidemiological data. METHODOLOGY: We studied two independently ascertained cohorts from the Polish background population (N∼3000 each and determined carrier rates of common ARSA gene mutations: c.459+1G>A, p.P426L, p.I179S (cohort 1 and c.459+1G>A, p.I179S (cohort 2. PRINCIPAL FINDINGS: Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses was estimated as 4.0/100,000 and 4.1/100,000, respectively for the 1(st and the 2(nd cohort with a pooled estimate of 4.1/100,000 (CI: 1.8-9.4 which was higher than the estimate of 0.38 per 100,000 live births based on diagnosed cases. The p.I179S mutation was relatively more prevalent among controls than patients (OR = 3.6, P = 0.0082, for a comparison of p.I179S frequency relative to c.459+1G>A between controls vs. patients. CONCLUSIONS/SIGNIFICANCE: The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population. The underdiagnosis rate may be particularly high among patients with p.I179S mutation whose disease is characterized mainly by psychotic symptoms.

Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

KAUST Repository

Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

2012-01-01

Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

KAUST Repository

Cui, Peng

2012-03-23

Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

Chronical influence of radiation and lead on mutation rates in plants of Arabidopsis Thaliana (L.) Heynh

International Nuclear Information System (INIS)

Kryukov, V.I.; Shishkin, V.A.; Sokolenko, S.F.

1996-01-01

Plants of Arabidopsis thaliana were grown in a laboratory conditions on the soil (black earth, chernozem) which was polluted with a radioactive isotopes of cesium, 134+137 Cs. Increase in specific activity of samples from 217 to 1025 and 2529 Bq/kg resulted in increase of embryonic mutation rate in Arabidopsis from 8.2 to 20.2 and 51.6 % respectively. Bringing Pb 2+ in a dose of 16 mg into the soil resulted in statistically significant decrease in mutation rate. Further increase of lead concentration in radioactive soils to 32, 64, 96, 160 and 320 mg/kg resulted in growth of the mutation rates in the plants which were grown on the soil with low and middle specific activity of cesium, and in decrease of the mutation rates in the plants which were grown on the soil with high specific radioactivity. The last process apparently was connected with the intensive growth in the number of sterile seeds in the pods. 19 refs.; 2 figs.; 4 tabs

Optimization of an Autonomous Car Controller Using a Self-Adaptive Evolutionary Strategy

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Tae Seong Kim

2012-09-01

Full Text Available Autonomous cars control the steering wheel, acceleration and the brake pedal, the gears and the clutch using sensory information from multiple sources. Like a human driver, it understands the current situation on the roads from the live streaming of sensory values. The decision-making module often suffers from the limited range of sensors and complexity due to the large number of sensors and actuators. Because it is tedious and difficult to design the controller manually from trial-and-error, it is desirable to use intelligent optimization algorithms. In this work, we propose optimizing the parameters of an autonomous car controller using self-adaptive evolutionary strategies (SAESs which co-evolve solutions and mutation steps for each parameter. We also describe how the most generalized parameter set can be retrieved from the process of optimization. Open-source car racing simulation software (TORCS is used to test the goodness of the proposed methods on 6 different tracks. Experimental results show that the SAES is competitive with the manual design of authors and a simple ES.

Programming adaptive control to evolve increased metabolite production.

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Chou, Howard H; Keasling, Jay D

2013-01-01

The complexity inherent in biological systems challenges efforts to rationally engineer novel phenotypes, especially those not amenable to high-throughput screens and selections. In nature, increased mutation rates generate diversity in a population that can lead to the evolution of new phenotypes. Here we construct an adaptive control system that increases the mutation rate in order to generate diversity in the population, and decreases the mutation rate as the concentration of a target metabolite increases. This system is called feedback-regulated evolution of phenotype (FREP), and is implemented with a sensor to gauge the concentration of a metabolite and an actuator to alter the mutation rate. To evolve certain novel traits that have no known natural sensors, we develop a framework to assemble synthetic transcription factors using metabolic enzymes and construct four different sensors that recognize isopentenyl diphosphate in bacteria and yeast. We verify FREP by evolving increased tyrosine and isoprenoid production.

Genetic Adaptation to Growth Under Laboratory Conditions in Escherichia coli and Salmonella enterica

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Anna Knöppel

2018-04-01

Full Text Available Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation, but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

Experimental estimation of mutation rates in a wheat population with a gene genealogy approach.

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Raquin, Anne-Laure; Depaulis, Frantz; Lambert, Amaury; Galic, Nathalie; Brabant, Philippe; Goldringer, Isabelle

2008-08-01

Microsatellite markers are extensively used to evaluate genetic diversity in natural or experimental evolving populations. Their high degree of polymorphism reflects their high mutation rates. Estimates of the mutation rates are therefore necessary when characterizing diversity in populations. As a complement to the classical experimental designs, we propose to use experimental populations, where the initial state is entirely known and some intermediate states have been thoroughly surveyed, thus providing a short timescale estimation together with a large number of cumulated meioses. In this article, we derived four original gene genealogy-based methods to assess mutation rates with limited bias due to relevant model assumptions incorporating the initial state, the number of new alleles, and the genetic effective population size. We studied the evolution of genetic diversity at 21 microsatellite markers, after 15 generations in an experimental wheat population. Compared to the parents, 23 new alleles were found in generation 15 at 9 of the 21 loci studied. We provide evidence that they arose by mutation. Corresponding estimates of the mutation rates ranged from 0 to 4.97 x 10(-3) per generation (i.e., year). Sequences of several alleles revealed that length polymorphism was only due to variation in the core of the microsatellite. Among different microsatellite characteristics, both the motif repeat number and an independent estimation of the Nei diversity were correlated with the novel diversity. Despite a reduced genetic effective size, global diversity at microsatellite markers increased in this population, suggesting that microsatellite diversity should be used with caution as an indicator in biodiversity conservation issues.

Self-Esteem and Social Adaptation Development in Children

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Alicia Lamia

2011-12-01

Full Text Available Self-esteem is the self-evaluation each individual makes from the representations it has of itself and from the representations constructed by the others. The sense of personal worth appears in a process of identity construction. This is associated with the assessment that people make about the social adaptation of the child. The present study concerns the development of self-image and self-esteem of children in school age. The sample consisted of 180 children. The results demonstrated a difference in the responses of children in relation to age and gender. The boys were evaluated more positively than girls. There has been the same results in younger children compared to the older ones.

PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a mammalian host.

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Czudai-Matwich, Volker; Otte, Anna; Matrosovich, Mikhail; Gabriel, Gülsah; Klenk, Hans-Dieter

2014-08-01

Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about the nearby mutations S714I and S714R, which have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine, and arginine at position 714 and compared them for polymerase activity and virus growth in avian and mammalian cells, as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote the adaptation of an H5N1 virus to a mammalian host. Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms that determine the host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study, we show that mutation S714R is also involved in adaptation and that it cooperates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus, where virus replication and transcription take place. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Characterization of a mutated Geobacillus stearothermophilus L-arabinose isomerase that increases the production rate of D-tagatose.

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Kim, H-J; Kim, J-H; Oh, H-J; Oh, D-K

2006-07-01

Characterization of a mutated Geobacillus stearothermophilus L-arabinose isomerase used to increase the production rate of D-tagatose. A mutated gene was obtained by an error-prone polymerase chain reaction using L-arabinose isomerase gene from G. stearothermophilus as a template and the gene was expressed in Escherichia coli. The expressed mutated L-arabinose isomerase exhibited the change of three amino acids (Met322-->Val, Ser393-->Thr, and Val408-->Ala), compared with the wild-type enzyme and was then purified to homogeneity. The mutated enzyme had a maximum galactose isomerization activity at pH 8.0, 65 degrees C, and 1.0 mM Co2+, while the wild-type enzyme had a maximum activity at pH 8.0, 60 degrees C, and 1.0-mM Mn2+. The mutated L-arabinose isomerase exhibited increases in D-galactose isomerization activity, optimum temperature, catalytic efficiency (kcat/Km) for D-galactose, and the production rate of D-tagatose from D-galactose. The mutated L-arabinose isomerase from G. stearothermophilus is valuable for the commercial production of D-tagatose. This work contributes knowledge on the characterization of a mutated L-arabinose isomerase, and allows an increased production rate for D-tagatose from D-galactose using the mutated enzyme.

The effect of a change in mutation rate on the incidence of dominant and X-linked recessive disorders in man

International Nuclear Information System (INIS)

Childs, J.D.

1981-01-01

In order to assess the impact on man of a sustained change in mutation rate that might be caused by ionizing radiation or a chemical mutagen in the environment, it is important to determine the current incidence of genetic disease, the rate at which deleterious mutations arise and the number of generations that mutations persist before eliminated by selection. From these data it should be possible to estimate both the increase in genetic disease in the first generation following the increase in mutation rate, and the rate at which a new equilibrium between mutation and selection would occur. In this paper the results of a survey to determine birth frequency, mutation rate and reproductive fitness for each of the important dominant and X-linked recessive disorders are described. It is estimated that these disorders affect about 0.6% of live-born individuals, including 0.1% of live-borns who carry a newly-arising mutation. (orig.)

Executive Function and Adaptive Behavior in Muenke Syndrome.

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Yarnell, Colin M P; Addissie, Yonit A; Hadley, Donald W; Guillen Sacoto, Maria J; Agochukwu, Nneamaka B; Hart, Rachel A; Wiggs, Edythe A; Platte, Petra; Paelecke, Yvonne; Collmann, Hartmut; Schweitzer, Tilmann; Kruszka, Paul; Muenke, Maximilian

2015-08-01

To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (General Executive Composite and the ABAS-II General Adaptive Composite. Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings. Published by Elsevier Inc.

Spontaneous mutation rate in Chinese hamster cell clones differing in UV-sensitivity

International Nuclear Information System (INIS)

Manuilova, E.S.; Bagrova, A.M.; Moskovskij Gosudarstvennyj Univ.

1983-01-01

The spontaneous rate of appearance of mutations to 6-mercaptopurine (6 MP) resistence in the cells of CHR2 and CHs2 clones dofferent in sensitivity to lethal and matagenous effect of UV-rays, is investigated. Increased UV-sensitivity of CHs2 clone is caused by the violation of postreplicative DNA reparation. It is established that the purity of spontaneously occuring mutations in both clones turns out to be similar, i.e. (1.5-1.8)x10 -5 for the cell pergeneration. It is shown that the effect of postreplicative DNA reparation in the cells of chinese hamster is not connected with the increase of spontaneous mutation ability. The problem on the possible role of reparation in the mechanism of appearance of spontaneous and induced mutations in the cells of Chinese hamster with increased UV-sensitivity is discussed

Selection and adaptation in irradiated plant and animal populations: a review

International Nuclear Information System (INIS)

Hart, D.R.

1981-03-01

Available literature on the effects of ionizing radiation on mutation rates, variability and adaptive responses to selection in exposed plant and animal populations is reviewed. Accumulated variability, and hence potential selection differentials, may be increased by many times due to induced mutation. The radiation dose that maximizes induced mutation varies greatly among species, strains and genetic systems. Induced variability tends to enhance the respose to selection, but this effect may be delayed or prevented by an initial reduction in the heritability of induced variation. Significantly, the detrimental effects of harmful mutations in irradiated populations may exceed the beneficial effects of selection for adaptive characteristics. Selection for radioresistance may occur at lethal or sub-lethal radiation doses but dose relationships are highly variable. (author)

Nanostructural self-organization and dynamic adaptation of metal-polymer tribosystems

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Mashkov, Yu. K.

2017-02-01

The results of investigating the effect of nanosize modifiers of a polymer matrix on the nanostructural self-organization of polymer composites and dynamic adaptation of metal-polymer tribosystems, which considerably affect the wear resistance of polymer composite materials, have been analyzed. It has been shown that the physicochemical nanostructural self-organization processes are developed in metal-polymer tribosystems with the formation of thermotropic liquid-crystal structures of the polymer matrix, followed by the transition of the system to the stationary state with a negative feedback that ensures dynamic adaptation of the tribosystem to given operating conditions.

The relationship of self-rated function and self-rated health to concurrent functional ability, functional decline, and mortality: findings from the Nun Study.

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Greiner, P A; Snowdon, D A; Greiner, L H

1996-09-01

We investigated the relationship of self-rated function (i.e., the ability to take care of oneself) and self-rated health to concurrent functional ability, functional decline, and mortality in participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. A total of 629 of the 678 study participants self-rated their function and health and completed an initial functional assessment in 1991-93. Survivors completed a second assessment in 1993-94. Overall, self-rated function had a stronger relationship to functional ability at the first assessment and to functional decline between the first and second assessments than did self-rated health. Self-rated function also had a stronger relationship to mortality than did self-rated health. Self-rated function may be a better marker of global function than is self-rated health and may be a useful addition to clinical assessment and scientific investigation of the relationships among function, health, and disease.

RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

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Perfeito, L; Sousa, A; Bataillon, T; Gordo, I

2014-01-01

Unraveling the factors that determine the rate of adaptation is a major question in evolutionary biology. One key parameter is the effect of a new mutation on fitness, which invariably depends on the environment and genetic background. The fate of a mutation also depends on population size, which determines the amount of drift it will experience. Here, we manipulate both population size and genotype composition and follow adaptation of 23 distinct Escherichia coli genotypes. These have previously accumulated mutations under intense genetic drift and encompass a substantial fitness variation. A simple rule is uncovered: the net fitness change is negatively correlated with the fitness of the genotype in which new mutations appear—a signature of epistasis. We find that Fisher's geometrical model can account for the observed patterns of fitness change and infer the parameters of this model that best fit the data, using Approximate Bayesian Computation. We estimate a genomic mutation rate of 0.01 per generation for fitness altering mutations, albeit with a large confidence interval, a mean fitness effect of mutations of −0.01, and an effective number of traits nine in mutS− E. coli. This framework can be extended to confront a broader range of models with data and test different classes of fitness landscape models. PMID:24372601

Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene.

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Pep Charusanti

2010-11-01

Full Text Available Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi by adaptively evolving ten replicates of E. coli lacking pgi for 50 days in glucose M9 minimal medium and by characterizing endpoint clones through whole-genome re-sequencing and phenotype profiling. We found that 1 the growth rates for all ten endpoint clones increased approximately 3-fold over the 50-day period; 2 two to five mutations arose during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and pntAB and in the stress-associated sigma factor rpoS; and 3 despite similar growth rates, at least three distinct endpoint phenotypes developed as defined by different rates of acetate and formate secretion. These results demonstrate that E. coli can adapt to the loss of a major metabolic gene product with only a handful of mutations and that adaptation can result in multiple, alternative phenotypes.

Rapid Genetic Adaptation during the First Four Months of Survival under Resource Exhaustion.

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Avrani, Sarit; Bolotin, Evgeni; Katz, Sophia; Hershberg, Ruth

2017-07-01

Many bacteria, including the model bacterium Escherichia coli can survive for years within spent media, following resource exhaustion. We carried out evolutionary experiments, followed by whole genome sequencing of hundreds of evolved clones to study the dynamics by which E. coli adapts during the first 4 months of survival under resource exhaustion. Our results reveal that bacteria evolving under resource exhaustion are subject to intense selection, manifesting in rapid mutation accumulation, enrichment in functional mutation categories and extremely convergent adaptation. In the most striking example of convergent adaptation, we found that across five independent populations adaptation to conditions of resource exhaustion occurs through mutations to the three same specific positions of the RNA polymerase core enzyme. Mutations to these three sites are strongly antagonistically pleiotropic, in that they sharply reduce exponential growth rates in fresh media. Such antagonistically pleiotropic mutations, combined with the accumulation of additional mutations, severely reduce the ability of bacteria surviving under resource exhaustion to grow exponentially in fresh media. We further demonstrate that the three positions at which these resource exhaustion mutations occur are conserved for the ancestral E. coli allele, across bacterial phyla, with the exception of nonculturable bacteria that carry the resource exhaustion allele at one of these positions, at very high frequencies. Finally, our results demonstrate that adaptation to resource exhaustion is not limited by mutational input and that bacteria are able to rapidly adapt under resource exhaustion in a temporally precise manner through allele frequency fluctuations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Adapting to Adaptations: Behavioural Strategies that are Robust to Mutations and Other Organisational-Transformations

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Egbert, Matthew D.; Pérez-Mercader, Juan

2016-01-01

Genetic mutations, infection by parasites or symbionts, and other events can transform the way that an organism’s internal state changes in response to a given environment. We use a minimalistic computational model to support an argument that by behaving “interoceptively,” i.e. responding to internal state rather than to the environment, organisms can be robust to these organisational-transformations. We suggest that the robustness of interoceptive behaviour is due, in part, to the asymmetrical relationship between an organism and its environment, where the latter more substantially influences the former than vice versa. This relationship means that interoceptive behaviour can respond to the environment, the internal state and the interaction between the two, while exteroceptive behaviour can only respond to the environment. We discuss the possibilities that (i) interoceptive behaviour may play an important role of facilitating adaptive evolution (especially in the early evolution of primitive life) and (ii) interoceptive mechanisms could prove useful in efforts to create more robust synthetic life-forms. PMID:26743579

Self-Reported Sleep Duration and Self-Rated Health in Young Adults.

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Štefan, Lovro; Juranko, Dora; Prosoli, Rebeka; Barić, Renata; Sporiš, Goran

2017-07-15

This study aimed to determine the associations between the self-reported sleep duration and self-rated health in young adults. In this cross-sectional study, participants were 689 young adults (mean age 20 ± 1.35 years, 49.8% female). Sleep duration and self-rated health, as the main outcome of interest, were measured as self-reported. As potential covariates, we included sex, age, smoking status, alcohol consumption, physical activity, sedentary behavior, psychological distress, and body mass index. Approximately 30% of participants slept 7-8 hours, 17.4% were short sleepers (categories 10 hours of sleep). In an unadjusted model, compared with the reference category (7-8 hours of sleep), those who slept health. In an adjusted model, short (sleep (> 10 hours) were both associated with poor self-rated health. Our results suggest that both short ( 10 hours) sleepers have lower odds of having good self-rated health after adjusting for potential covariates. Health professionals should pay more attention to young adults, who have both short and long period of sleep, in order to prevent health problems and potential acute or chronic diseases. © 2017 American Academy of Sleep Medicine

A Rate Adaptation Scheme According to Channel Conditions in Wireless LANs

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Numoto, Daisuke; Inai, Hiroshi

Rate adaptation in wireless LANs is to select the most suitable transmission rate automatically according to channel condition. If the channel condition is good, a station can choose a higher transmission rate, otherwise, it should choose a lower but noise-resistant transmission rate. Since IEEE 802.11 does not specify any rate adaptation scheme, several schemes have been proposed. However those schemes provide low throughput or unfair transmission opportunities among stations especially when the number of stations increases. In this paper, we propose a rate adaptation scheme under which the transmission rate quickly closes and then stays around an optimum rate even in the presence of a large number of stations. Via simulation, our scheme provides higher throughput than existing ones and almost equal fairness.

Effects of Self-Rated Health and Self-Rated Economic Situation on Depressed Mood Via Life Satisfaction Among Older Adults in Costa Rica

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Reyes Fernández, Benjamín; Rosero-Bixby, Luis; Koivumaa-Honkanen, Heli

2016-01-01

Objective: The study examined the relationship of self-rated health and self-rated economic situation with depressed mood, and life satisfaction as mediator of this relationship among older adults in Costa Rica. Method: A longitudinal study was conducted with a subsample (N = 1,618) from the Costa Rican Longevity and Healthy Aging Study (CRELES). Self-rated health, self-rated economic situation, depressed mood, and life satisfaction were measured at baseline, and depressed mood was reassessed 18 months later. Putative mechanisms for changes in depressed mood were examined by means of conditional process analysis. Results: Self-rated health was negatively associated to depressed mood. This effect took place via life satisfaction. An interaction showed that better economic situation compensated the effect of a low self-rated health on life satisfaction. Discussion: This study suggests that subjective variables such as self-rated health, economic situation, and life satisfaction should be considered when addressing the onset of depressed mood. PMID:26092651

Can models of self-management support be adapted across cancer types? A comparison of unmet self-management needs for patients with breast or colorectal cancer.

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Mansfield, Elise; Mackenzie, Lisa; Carey, Mariko; Peek, Kerry; Shepherd, Jan; Evans, Tiffany-Jane

2018-03-01

There is an increased focus on supporting patients with cancer to actively participate in their healthcare, an approach commonly termed 'self-management'. Comparing unmet self-management needs across cancer types may reveal opportunities to adapt effective self-management support strategies from one cancer type to another. Given that breast and colorectal cancers are prevalent, and have high survival rates, we compared these patients' recent need for help with self-management. Data on multiple aspects of self-management were collected from 717 patients with breast cancer and 336 patients with colorectal cancer attending one of 13 Australian medical oncology treatment centres. There was no significant difference between the proportion of patients with breast or colorectal cancer who reported a need for help with at least one aspect of self-management. Patients with breast cancer were significantly more likely to report needing help with exercising more, while patients with colorectal cancer were more likely to report needing help with reducing alcohol consumption. When controlling for treatment centre, patients who were younger, experiencing distress or had not received chemotherapy were more likely to report needing help with at least one aspect of self-management. A substantial minority of patients reported an unmet need for self-management support. This indicates that high-quality intervention research is needed to identify effective self-management support strategies, as well as implementation trials to identify approaches to translating these strategies into practice. Future research should continue to explore whether self-management support strategies could be adapted across cancer types.

Characteristics of self-rating and rating by others of safety behavior

International Nuclear Information System (INIS)

Fukui, Hirokazu; Yoshida, Michio; Sugiman, Toshio; Watanabe, Toshie

2002-01-01

It is known that in questionnaire surveys in general, behavior that are recognized as socially desirable are more highly rated by the actors themselves than by others. Safety behavior can be viewed as behavior closely related to social desirability. Therefore, in the present study, multiple regression analysis was conducted to examine how the self-rating and rating by others of 'safety confirmation/report', which serves as one of the rating scales of safety climate and criterion for safety behavior rating, are related to other factors of safety climate. The analysis results reveal that the self-rating of 'safety confirmation/report' tends to give better scores than rating by others and is more strongly related to individual factors than organizational environmental factors. Meanwhile, the rating by others of safety confirmation/report' is strongly related to organizational environmental factors and demonstrates little or no link with individual factors. It can be said, therefore, that the rating by others of 'safety confirmation/report' reflects more accurately the influence of the organizational environment concerned than self-rating, and hence is more appropriate as a rating scale for safety climate. (author)

Characteristics of self-rating and rating by others of safety behavior

Energy Technology Data Exchange (ETDEWEB)

Fukui, Hirokazu [Institute of Nuclear Safety System, Inc., Mihama, Fukui (Japan); Yoshida, Michio; Sugiman, Toshio; Watanabe, Toshie [Japan Institute for Group Dynamics, Fukuoka (Japan)

2002-09-01

It is known that in questionnaire surveys in general, behavior that are recognized as socially desirable are more highly rated by the actors themselves than by others. Safety behavior can be viewed as behavior closely related to social desirability. Therefore, in the present study, multiple regression analysis was conducted to examine how the self-rating and rating by others of 'safety confirmation/report', which serves as one of the rating scales of safety climate and criterion for safety behavior rating, are related to other factors of safety climate. The analysis results reveal that the self-rating of 'safety confirmation/report' tends to give better scores than rating by others and is more strongly related to individual factors than organizational environmental factors. Meanwhile, the rating by others of safety confirmation/report' is strongly related to organizational environmental factors and demonstrates little or no link with individual factors. It can be said, therefore, that the rating by others of 'safety confirmation/report' reflects more accurately the influence of the organizational environment concerned than self-rating, and hence is more appropriate as a rating scale for safety climate. (author)

Self-Rated Competences Questionnaires from a Design Perspective

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Braun, Edith; Woodley, Alan; Richardson, John T. E.; Leidner, Bernhard

2012-01-01

This paper provides a theoretical review of self-rated competences questionnaires. This topic is influenced by the ongoing world-wide reform of higher education, which has led to a focus on the learner outcomes of higher education. Consequently, questionnaires on self-rated competences have increasingly been employed. However, self-ratings are…

Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

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Kyleen Luhrs

2017-01-01

Full Text Available The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62, de novo deletion copy number variations (DEL, n=74, de novo likely gene-disrupting mutations (LGDM, n=267, and children without a known genetic etiology (NON, n=2111. Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact

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Taylor, Jared F.; Khattab, Omar S.; Chen, Yu-Han; Chen, Yumay; Jacobsen, Steven E.; Wang, Ping H.

2015-01-01

Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer. PMID:26308346

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

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Puya G Yazdi

Full Text Available Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp and end (115 bp of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

Adapting to an initial self-regulatory task cancels the ego depletion effect.

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Dang, Junhua; Dewitte, Siegfried; Mao, Lihua; Xiao, Shanshan; Shi, Yucai

2013-09-01

The resource-based model of self-regulation provides a pessimistic view of self-regulation that people are destined to lose their self-control after having engaged in any act of self-regulation because these acts deplete the limited resource that people need for successful self-regulation. The cognitive control theory, however, offers an alternative explanation and suggests that the depletion effect reflects switch costs between different cognitive control processes recruited to deal with demanding tasks. This account implies that the depletion effect will not occur once people have had the opportunity to adapt to the self-regulatory task initially engaged in. Consistent with this idea, the present study showed that engaging in a demanding task led to performance deficits on a subsequent self-regulatory task (i.e. the depletion effect) only when the initial demanding task was relatively short but not when it was long enough for participants to adapt. Our results were unrelated to self-efficacy, mood, and motivation. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutational jackpot events generate effective frequency-dependent selection in adapting populations

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Hallatschek, Oskar

The site-frequency spectrum is one the most easily measurable quantities that characterize the genetic diversity of a population. While most neutral models predict that site frequency spectra should decay with increasing frequency, a high-frequency uptick has been reported in many populations. Anomalies in the high-frequency tail are particularly unsettling because the highest frequencies can be measured with greatest accuracy. Here, we show that an uptick in the spectrum of neutral mutations generally arises when mutant frequencies are dominated by rare jackpot events, mutational events with large descendant numbers. This leads to an effective pattern of frequency-dependent selection (or unstable internal equilibrium at one half frequency) that causes an accumulation of high-frequency polymorphic sites. We reproduce the known uptick occurring for recurrent hitchhiking (genetic draft) as well as rapid adaptation, and (in the future) generalize the shape of the high-frequency tail to other scenarios that are dominated by jackpot events, such as frequent range expansions. We also tackle (in the future) the inverse approach to use the high-frequency uptick for learning about the tail of the offspring number distribution. Positively selected alleles need to surpass, typically, an u NSF Career Award (PoLS), NIH NIGMS R01, Simons Foundation.

Optimal Mutation Rates for the (1+lambda) EA on OneMax Through Asymptotically Tight Drift Analysis

DEFF Research Database (Denmark)

Gießen, Christian; Witt, Carsten

2018-01-01

We study the (1+) EA, a classical population-based evolutionary algorithm, with mutation probability c / n, where and are constant, on the benchmark function OneMax, which counts the number of 1-bits in a bitstring. We improve a well-established result that allows to determine the first hitting t...... that mutation rates up to 10% larger than the asymptotically optimal rate 1 / n minimize the expected runtime. However, in absolute terms the expected runtime does not change by much when replacing 1 / n with the optimal mutation rate....... drift is known. This reduces the analysis of expected optimization time to finding an exact expression for the drift. We then give an exact closed-form expression for the drift and develop a method to approximate it very efficiently, enabling us to determine approximate optimal mutation rates for the (1......+) EA for various parameter settings of c and and also for moderate sizes of n. This makes the need for potentially lengthy and costly experiments in order to optimize c for fixed n and for the optimization of OneMax unnecessary. Interestingly, even for moderate n and not too small it turns out...

Adaptive complementary fuzzy self-recurrent wavelet neural network controller for the electric load simulator system

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Wang Chao

2016-03-01

Full Text Available Due to the complexities existing in the electric load simulator, this article develops a high-performance nonlinear adaptive controller to improve the torque tracking performance of the electric load simulator, which mainly consists of an adaptive fuzzy self-recurrent wavelet neural network controller with variable structure (VSFSWC and a complementary controller. The VSFSWC is clearly and easily used for real-time systems and greatly improves the convergence rate and control precision. The complementary controller is designed to eliminate the effect of the approximation error between the proposed neural network controller and the ideal feedback controller without chattering phenomena. Moreover, adaptive learning laws are derived to guarantee the system stability in the sense of the Lyapunov theory. Finally, the hardware-in-the-loop simulations are carried out to verify the feasibility and effectiveness of the proposed algorithms in different working styles.

Age-related increase in the rate of spontaneou and γ-ray-induced hprt mutations in mouse spleen lymphocytes

International Nuclear Information System (INIS)

Gazlev, A.I.; Podlutskii, A.Ya.; Bradbury, R.

1994-01-01

Endogenous and exogenous factors continually afflict DNA of cells of organisms. A certain amount of the damage is accumulated causing mutations, increasing the risk of malignacies, impairing cell functions, and upsetting the body's homeostasis. The research reported here studies the rates of spontaneous hprt nmutationsand those induced you ggammairradiation in the splenocytes of mice at various ages. The rate of spontaneous and induced hprt gene mutations increases with aging. In gamma irradiated mice the rate of radiation-induced mutations depended on the absorbed dose and age, with the rate 2.3-3.0 fold higher in 104-110 week old mice than in younger pups. 15 refs., 1 tab

Parent and Self-Report Ratings on the Perceived Levels of Social Vulnerability of Adults with Williams Syndrome

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Lough, Emma; Fisher, Marisa H.

2016-01-01

The current study took a multi-informant approach to compare parent to self-report ratings of social vulnerability of adults with Williams syndrome (WS). Participants included 102 pairs of adults with WS and their parents. Parents completed the "Social Vulnerability Questionnaire" and adults with WS completed an adapted version of the…

Cancer-specific self-efficacy and psychosocial and functional adaptation to early stage breast cancer.

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Manne, Sharon L; Ostroff, Jamie S; Norton, Tina R; Fox, Kevin; Grana, Generosa; Goldstein, Lori

2006-04-01

Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer. To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of self-efficacy and specific psychological, relationship, and functional outcomes. Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later. Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy-(a) Activity Management and (b) Self-Satisfaction-evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later. Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

Self: an adaptive pressure arising from self-organization, chaotic dynamics, and neural Darwinism.

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Bruzzo, Angela Alessia; Vimal, Ram Lakhan Pandey

2007-12-01

In this article, we establish a model to delineate the emergence of "self" in the brain making recourse to the theory of chaos. Self is considered as the subjective experience of a subject. As essential ingredients of subjective experiences, our model includes wakefulness, re-entry, attention, memory, and proto-experiences. The stability as stated by chaos theory can potentially describe the non-linear function of "self" as sensitive to initial conditions and can characterize it as underlying order from apparently random signals. Self-similarity is discussed as a latent menace of a pathological confusion between "self" and "others". Our test hypothesis is that (1) consciousness might have emerged and evolved from a primordial potential or proto-experience in matter, such as the physical attractions and repulsions experienced by electrons, and (2) "self" arises from chaotic dynamics, self-organization and selective mechanisms during ontogenesis, while emerging post-ontogenically as an adaptive pressure driven by both volume and synaptic-neural transmission and influencing the functional connectivity of neural nets (structure).

Self-rated Driving and Driving Safety in Older Adults

OpenAIRE

Ross, Lesley A.; Dodson, Joan; Edwards, Jerri D.; Ackerman, Michelle L.; Ball, Karlene

2012-01-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults’ self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving...

Self-esteem, stress and self-rated health in family planning clinic patients

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Young Rodney

2004-06-01

Full Text Available Abstract Background The independent effects of stress on the health of primary care patients might be different for different types of clinic populations. This study examines these relationships in a low-income female population of patients attending a family planning clinic. Methods This study investigated the relevance of different sources of personal stress and social support to self-rated health, adjusting for mental health, health behavior and demographic characteristics of subjects. Five hundred women who attended family planning clinics were surveyed and 345 completed the form for a response rate of 72 percent. Results Multiple logistic regression analysis revealed that liking oneself was related to good self-rated health (Odds ratio = 7.11, but stress or support from children, parents, friends, churches or spouses were not significant. White non-Hispanic and non-white non-Hispanic respondents had lower odds of reporting good self-rated health than Hispanic respondents (odds ratios were 2.87 and 2.81, respectively. Exercising five or more days per week also was related to good self-rated health. Smoking 20 or more cigarettes per day, and obese III were negatively related to good self-rated health (odds ratios were .19 and .22, respectively with corresponding p-values equal to .0043 and .0332. Conclusions Among younger low-income women, addressing low self-esteem might improve health status.

Chronic condition self-management support for Aboriginal people: Adapting tools and training.

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Battersby, Malcolm; Lawn, Sharon; Kowanko, Inge; Bertossa, Sue; Trowbridge, Coral; Liddicoat, Raylene

2018-04-22

Chronic conditions are major health problems for Australian Aboriginal people. Self-management programs can improve health outcomes. However, few health workers are skilled in self-management support and existing programs are not always appropriate in Australian Aboriginal contexts. The goal was to increase the capacity of the Australian health workforce to support Australian Aboriginal people to self-manage their chronic conditions by adapting the Flinders Program of chronic condition self-management support for Australian Aboriginal clients and develop and deliver training for health professionals to implement the program. Feedback from health professionals highlighted that the Flinders Program assessment and care planning tools needed to be adapted to suit Australian Aboriginal contexts. Through consultation with Australian Aboriginal Elders and other experts, the tools were condensed into an illustrated booklet called 'My Health Story'. Associated training courses and resources focusing on cultural safety and effective engagement were developed. A total of 825 health professionals  across Australia was trained and 61 people qualified as accredited trainers in the program, ensuring sustainability. The capacity and skills of the Australian health workforce to engage with and support Australian Aboriginal people to self-manage their chronic health problems significantly increased as a result of this project. The adapted tools and training were popular and appreciated by the health care organisations, health professionals and clients involved. The adapted tools have widespread appeal for cultures that do not have Western models of health care and where there are health literacy challenges. My Health Story has already been used internationally. © 2018 National Rural Health Alliance Ltd.

Control of beam halo-chaos using neural network self-adaptation method

International Nuclear Information System (INIS)

Fang Jinqing; Huang Guoxian; Luo Xiaoshu

2004-11-01

Taking the advantages of neural network control method for nonlinear complex systems, control of beam halo-chaos in the periodic focusing channels (network) of high intensity accelerators is studied by feed-forward back-propagating neural network self-adaptation method. The envelope radius of high-intensity proton beam is reached to the matching beam radius by suitably selecting the control structure of neural network and the linear feedback coefficient, adjusted the right-coefficient of neural network. The beam halo-chaos is obviously suppressed and shaking size is much largely reduced after the neural network self-adaptation control is applied. (authors)

Genetic influence of radiation measured by the effect on the mutation rate of human minisatellite genes

International Nuclear Information System (INIS)

Kodaira, Mieko

2002-01-01

Human minisatellite genes are composed from 0.1-30 kb with a high frequency of polymorphism. The genes exist in mammalian genomes and mice's ones are well studied after irradiation of their gonad cells by X-ray and γ-ray. Following five reports concerning the significant and/or insignificant increases of the mutation rate of the genes post A-bomb exposure, Chernobyl accident and nuclear weapons test in Semipalatinsk are reviewed and discussed on the subject number, exposed dose, problems of the control group, regions examined of loci and exposure conditions. Genetic influences of radiation examined by the author's facility are not recognized in the mutation rate (3.21% vs 4.94% in the control) of minisatellite genes in children of A-bomb survivors and their parents. The mutation rates are 4.27 vs 2.52% (positive influence) and 4.2-6.01% vs 3.5-6.34% in Chernobyl, and 4.3 (parents) and 3.8% (F 1 ) vs 2.5% (positive). Mutation of human minisatellite genes can be an important measure of genetic influences at the medical level. (K.H.)

Psychological Adaptation, Marital Satisfaction, and Academic Self-Efficacy of International Students

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Bulgan, Gökçe; Çiftçi, Ayse

2017-01-01

The authors investigated marital satisfaction and academic self-efficacy in relation to psychological adaptation (i.e., psychological well-being, life satisfaction) in a sample of 198 married international students. Results of multiple regression analyses indicated that marital satisfaction and academic self-efficacy accounted for 45.9% of…

Measuring the prevalence of regional mutation rates: an analysis of silent substitutions in mammals, fungi, and insects

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Tuch Brian B

2008-06-01

Full Text Available Abstract Background The patterns of mutation vary both within and across genomes. It has been shown for a few mammals that mutation rates vary within the genome, while for unknown reasons, the sensu stricto yeasts have uniform rates instead. The generality of these observations has been unknown. Here we examine silent site substitutions in a more expansive set (20 mammals, 27 fungi, 4 insects to determine why some genomes demonstrate this mosaic distribution and why others are uniform. Results We applied several intragene and intergene correlation tests to measure regional substitution patterns. Assuming that silent sites are a reasonable approximation to neutrally mutating sequence, our results show that all multicellular eukaryotes exhibit mutational heterogeneity. In striking contrast, all fungi are mutationally uniform – with the exception of three Candida species: C. albicans, C. dubliniensis, and C. tropicalis. We speculate that aspects of replication timing may be responsible for distinguishing these species. Our analysis also reveals classes of genes whose silent sites behave anomalously with respect to the mutational background in many species, indicating prevalent selective pressures. Genes associated with nucleotide binding or gene regulation have consistently low silent substitution rates in every mammalian species, as well as multiple fungi. On the other hand, receptor genes repeatedly exhibit high silent substitution rates, suggesting they have been influenced by diversifying selection. Conclusion Our findings provide a framework for understanding the regional mutational properties of eukaryotes, revealing a sharp difference between fungi and multicellular species. They also elucidate common selective pressures acting on eukaryotic silent sites, with frequent evidence for both purifying and diversifying selection.

Background Selection in Partially Selfing Populations

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Roze, Denis

2016-01-01

Self-fertilizing species often present lower levels of neutral polymorphism than their outcrossing relatives. Indeed, selfing automatically increases the rate of coalescence per generation, but also enhances the effects of background selection and genetic hitchhiking by reducing the efficiency of recombination. Approximations for the effect of background selection in partially selfing populations have been derived previously, assuming tight linkage between deleterious alleles and neutral loci. However, loosely linked deleterious mutations may have important effects on neutral diversity in highly selfing populations. In this article, I use a general method based on multilocus population genetics theory to express the effect of a deleterious allele on diversity at a linked neutral locus in terms of moments of genetic associations between loci. Expressions for these genetic moments at equilibrium are then computed for arbitrary rates of selfing and recombination. An extrapolation of the results to the case where deleterious alleles segregate at multiple loci is checked using individual-based simulations. At high selfing rates, the tight linkage approximation underestimates the effect of background selection in genomes with moderate to high map length; however, another simple approximation can be obtained for this situation and provides accurate predictions as long as the deleterious mutation rate is not too high. PMID:27075726

Genetic Adaptation to Salt Stress in Experimental Evolution of Desulfovibrio vulgaris Hildenborough

Energy Technology Data Exchange (ETDEWEB)

Zhou, Aifen; Hillesland, Kristina; He, Zhili; Joachimiak, Marcin; Zane, Grant; Dehal, Paramvir; Arkin, Adam; Stahl, David; Wall, Judy; Hazen, Terry; Zhou, Jizhong; Baidoo, Edward; Benke, Peter; Mukhopadhyay, Aindrila

2010-05-17

High salinity is one of the most common environmental stressors. In order to understand how environmental organisms adapt to salty environment, an experiment evolution with sulfate reducing bacteria Desulfovibrio vugaris Hildenborough was conducted. Control lines and salt-stressed lines (6 lines each) grown in minimal medium LS4D or LS4D + 100 mM NaCl were transferred for 1200 generations. The salt tolerance was tested with LS4D supplemented with 250 mM NaCl. Statistical analysis of the growth data suggested that all lines adapted to their evolutionary environment. In addition, the control lines performed better than the ancestor with faster growth rate, higher biomass yield and shorter lag phase under salty environment they did not evolve in. However, the salt-adapted lines performed better than the control lines on measures of growth rate and yield under salty environment, suggesting that the salt?evolved lines acquired mutations specific to having extra salt in LS4D. Growth data and gene transcription data suggested that populations tended to improve till 1000 generations and active mutations tended to be fixed at the stage of 1000 generations. Point mutations and insertion/deletions were identified in isolated colonies from salt-adapted and control lines via whole genome sequencing. Glu, Gln and Ala appears to be the major osmoprotectant in evolved salt-stressed line. Ongoing studies are now characterizing the contribution of specific mutations identified in the salt-evolved D. vulgaris.

Predicting Career Adaptability through Self-Esteem and Social Support: A Research on Young Adults

Science.gov (United States)

Ataç, Lale Oral; Dirik, Deniz; Tetik, Hilmiye Türesin

2018-01-01

The purpose of this study is to investigate the relationship between career adaptability and self-esteem, and analyze the moderating role of social support in this relationship on a sample of 313 young adults. The results of the study confirm that career adaptability is significantly predicted by self-esteem. Moreover, findings suggest that (1)…

Self-rated driving and driving safety in older adults.

Science.gov (United States)

Ross, Lesley A; Dodson, Joan E; Edwards, Jerri D; Ackerman, Michelle L; Ball, Karlene

2012-09-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults' self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older adults (n=350; mean age 73.9, SD=5.25, range 65-91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14-0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>0.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults

A case study of evolutionary computation of biochemical adaptation

International Nuclear Information System (INIS)

François, Paul; Siggia, Eric D

2008-01-01

Simulations of evolution have a long history, but their relation to biology is questioned because of the perceived contingency of evolution. Here we provide an example of a biological process, adaptation, where simulations are argued to approach closer to biology. Adaptation is a common feature of sensory systems, and a plausible component of other biochemical networks because it rescales upstream signals to facilitate downstream processing. We create random gene networks numerically, by linking genes with interactions that model transcription, phosphorylation and protein–protein association. We define a fitness function for adaptation in terms of two functional metrics, and show that any reasonable combination of them will yield the same adaptive networks after repeated rounds of mutation and selection. Convergence to these networks is driven by positive selection and thus fast. There is always a path in parameter space of continuously improving fitness that leads to perfect adaptation, implying that the actual mutation rates we use in the simulation do not bias the results. Our results imply a kinetic view of evolution, i.e., it favors gene networks that can be learned quickly from the random examples supplied by mutation. This formulation allows for deductive predictions of the networks realized in nature

Population data and mutation rates of 20 autosomal STR loci in a Chinese Han population from Yunnan Province, Southwest China.

Science.gov (United States)

Zhang, Xiufeng; Liu, Linlin; Xie, Runfang; Wang, Guiyi; Shi, Yuan; Gu, Tao; Hu, Liping; Nie, Shengjie

2018-07-01

The genetic polymorphisms of 20 autosomal short tandem repeat (STR) loci included in the PowerPlex® 21 kit were evaluated from 2068 unrelated, healthy individuals from the Chinese Han population of Yunnan Province in southwest China. All of the loci reached Hardy-Weinberg equilibrium. These loci were examined to determine allele frequencies and forensic statistical parameters. The genetic relationships among the Yunnan Han and other Chinese populations were also estimated. The combined discrimination power and probability of excluding paternity of the 20 STR loci were 0.99999999999999999999999126 and 0.999999975, respectively. In addition, mutation rates from 4363 parentage cases (2215 trios and 2148 duos) were investigated in this study. A total of 164 mutations were observed in 6578 meioses from the 20 loci. The highest mutation rate was observed in D12S391 (0.30%), and the lowest mutation rates were observed in D13S317 (0.03%) and TPOX (0.03%). The average mutation rate for the 20 loci was estimated to be 1.246 × 10 -3 per meiosis. The mutations were primarily single-step and paternal mutations.

Quasi-CW diode-pumped self-starting adaptive laser with self-Q-switched output.

Science.gov (United States)

Smith, G; Damzen, M J

2007-05-14

An investigation is made into a quasi-CW (QCW) diode-pumped holographic adaptive laser utilising an ultra high gain (approximately 10(4)) Nd:YVO(4) bounce amplifier. The laser produces pulses at 1064 nm with energy approximately 0.6 mJ, duration laser configuration, the output was amplified to obtain pulses of approximately 5.6 mJ energy, approximately 7 ns duration and approximately 1 MW peak power. The output spatial quality is also M(2)diode-pumped self-adaptive holographic lasers can provide a useful source of high peak power, short duration pulses with excellent spatial quality and narrow linewidth spectrum.

Design optimization and analysis of selected thermal devices using self-adaptive Jaya algorithm

International Nuclear Information System (INIS)

Rao, R.V.; More, K.C.

2017-01-01

Highlights: • Self-adaptive Jaya algorithm is proposed for optimal design of thermal devices. • Optimization of heat pipe, cooling tower, heat sink and thermo-acoustic prime mover is presented. • Results of the proposed algorithm are better than the other optimization techniques. • The proposed algorithm may be conveniently used for the optimization of other devices. - Abstract: The present study explores the use of an improved Jaya algorithm called self-adaptive Jaya algorithm for optimal design of selected thermal devices viz; heat pipe, cooling tower, honeycomb heat sink and thermo-acoustic prime mover. Four different optimization case studies of the selected thermal devices are presented. The researchers had attempted the same design problems in the past using niched pareto genetic algorithm (NPGA), response surface method (RSM), leap-frog optimization program with constraints (LFOPC) algorithm, teaching-learning based optimization (TLBO) algorithm, grenade explosion method (GEM) and multi-objective genetic algorithm (MOGA). The results achieved by using self-adaptive Jaya algorithm are compared with those achieved by using the NPGA, RSM, LFOPC, TLBO, GEM and MOGA algorithms. The self-adaptive Jaya algorithm is proved superior as compared to the other optimization methods in terms of the results, computational effort and function evalutions.

Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309).

Science.gov (United States)

May, C A; Jeffreys, A J; Armour, J A

1996-11-01

Many tandemly repeated minisatellite loci display extreme levels of length variation as a consequence of high rates of spontaneous germline mutation altering repeat copy number. Direct screening for new allele lengths by small-pool PCR has shown that instability at the human minisatellite locus MS205 (D16S309) is largely germline specific and usually results in the gain or loss of just a few repeat units. Structural analysis of the order of variant repeats has shown that these events occur preferentially at one end of the tandem array and can result in complex rearrangements including the inter-allelic transfer of repeat units. In contrast, putative mutants recovered from somatic DNA occur at a substantially lower rate and are simple and non-polar in nature. Germline mutation rates vary considerably between alleles, consistent with regulation occurring in cis. Although examination of DNA sequence polymorphisms immediately flanking the minisatellite reveals no definitive associations with germline mutation rate variation, differences in rate may be paralleled by changes in mutation spectrum. These findings help to explain the diversity of MS205 allele structures in modern humans and suggest a common mutation pathway with some other minisatellites.

Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases.

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He, Xin; Chen, Zhigang; Jiang, Yangyan; Qiu, Xi; Zhao, Xiaoying

2013-01-25

The human c-mpl gene (MPL) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. However, numerous MPL mutations have been identified in haematopoietic diseases. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signalling deficiencies. In this review, we summarise 59 different MPL mutations and classify these mutations into four different groups according to the associated diseases and mutation rates. Using this classification, we clearly distinguish four diverse types of MPL mutations and obtain a deep understand of their clinical significance. This will prove to be useful for both disease diagnosis and the design of individual therapy regimens based on the type of MPL mutations.

Adaptation to the edge of chaos in a self-starting Kerr-lens mode-locked laser

Science.gov (United States)

Hsu, C. C.; Lin, J. H.; Hsieh, W. F.

2009-08-01

We experimentally and numerically demonstrated that self-focusing acts as a slow-varying control parameter that suppresses the transient chaos to reach a stable mode-locking (ML) state in a self-starting Kerr-lens mode-locked Ti:sapphire laser without external modulation and feedback control. Based on Fox-Li’s approach, including the self-focusing effect, the theoretical simulation reveals that the self-focusing effect is responsible for the self-adaptation. The self-adaptation occurs at the boundary between the chaotic and continuous output regions in which the laser system begins with a transient chaotic state with fractal correlation dimension, and then evolves with reducing dimension into the stable ML state.

Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

Science.gov (United States)

McCraty, Rollin; Shaffer, Fred

2015-01-01

Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

The dynamics of diverse segmental amplifications in populations of Saccharomyces cerevisiae adapting to strong selection.

Science.gov (United States)

Payen, Celia; Di Rienzi, Sara C; Ong, Giang T; Pogachar, Jamie L; Sanchez, Joseph C; Sunshine, Anna B; Raghuraman, M K; Brewer, Bonita J; Dunham, Maitreya J

2014-03-20

Population adaptation to strong selection can occur through the sequential or parallel accumulation of competing beneficial mutations. The dynamics, diversity, and rate of fixation of beneficial mutations within and between populations are still poorly understood. To study how the mutational landscape varies across populations during adaptation, we performed experimental evolution on seven parallel populations of Saccharomyces cerevisiae continuously cultured in limiting sulfate medium. By combining quantitative polymerase chain reaction, array comparative genomic hybridization, restriction digestion and contour-clamped homogeneous electric field gel electrophoresis, and whole-genome sequencing, we followed the trajectory of evolution to determine the identity and fate of beneficial mutations. During a period of 200 generations, the yeast populations displayed parallel evolutionary dynamics that were driven by the coexistence of independent beneficial mutations. Selective amplifications rapidly evolved under this selection pressure, in particular common inverted amplifications containing the sulfate transporter gene SUL1. Compared with single clones, detailed analysis of the populations uncovers a greater complexity whereby multiple subpopulations arise and compete despite a strong selection. The most common evolutionary adaptation to strong selection in these populations grown in sulfate limitation is determined by clonal interference, with adaptive variants both persisting and replacing one another.

Architecture and Knowledge-Driven Self-Adaptive Security in Smart Space

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Antti Evesti

2013-03-01

Full Text Available Dynamic and heterogeneous smart spaces cause challenges for security because it is impossible to anticipate all the possible changes at design-time. Self-adaptive security is an applicable solution for this challenge. This paper presents an architectural approach for security adaptation in smart spaces. The approach combines an adaptation loop, Information Security Measuring Ontology (ISMO and a smart space security-control model. The adaptation loop includes phases to monitor, analyze, plan and execute changes in the smart space. The ISMO offers input knowledge for the adaptation loop and the security-control model enforces dynamic access control policies. The approach is novel because it defines the whole adaptation loop and knowledge required in each phase of the adaptation. The contributions are validated as a part of the smart space pilot implementation. The approach offers reusable and extensible means to achieve adaptive security in smart spaces and up-to-date access control for devices that appear in the space. Hence, the approach supports the work of smart space application developers.

Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein.

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Benjamin Mänz

2013-03-01

Full Text Available The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP of pandemic strains A/Brevig Mission/1/1918 (1918 and A/Hamburg/4/2009 (pH1N1 that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1/04 (H5N1 resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

Effects of Rating Purpose and Rater Self-Esteem on Performance Ratings.

Science.gov (United States)

1983-03-01

examined in a laboratory study, using a 2x2 analysis of variance design. Results indicate that low self - esteem raters assign significantly higher...design. Results indicate that low self - esteem raters assign significantly higher performance ratings when performance appraisal information will be used...studies indicated that individuals low in self - esteem have less self -confidence, feel less competent, and rely more on others’ opinions than do individuals

Location-Based Self-Adaptive Routing Algorithm for Wireless Sensor Networks in Home Automation

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Hong SeungHo

2011-01-01

Full Text Available The use of wireless sensor networks in home automation (WSNHA is attractive due to their characteristics of self-organization, high sensing fidelity, low cost, and potential for rapid deployment. Although the AODVjr routing algorithm in IEEE 802.15.4/ZigBee and other routing algorithms have been designed for wireless sensor networks, not all are suitable for WSNHA. In this paper, we propose a location-based self-adaptive routing algorithm for WSNHA called WSNHA-LBAR. It confines route discovery flooding to a cylindrical request zone, which reduces the routing overhead and decreases broadcast storm problems in the MAC layer. It also automatically adjusts the size of the request zone using a self-adaptive algorithm based on Bayes' theorem. This makes WSNHA-LBAR more adaptable to the changes of the network state and easier to implement. Simulation results show improved network reliability as well as reduced routing overhead.

SAGE - MULTIDIMENSIONAL SELF-ADAPTIVE GRID CODE

Science.gov (United States)

Davies, C. B.

1994-01-01

SAGE, Self Adaptive Grid codE, is a flexible tool for adapting and restructuring both 2D and 3D grids. Solution-adaptive grid methods are useful tools for efficient and accurate flow predictions. In supersonic and hypersonic flows, strong gradient regions such as shocks, contact discontinuities, shear layers, etc., require careful distribution of grid points to minimize grid error and produce accurate flow-field predictions. SAGE helps the user obtain more accurate solutions by intelligently redistributing (i.e. adapting) the original grid points based on an initial or interim flow-field solution. The user then computes a new solution using the adapted grid as input to the flow solver. The adaptive-grid methodology poses the problem in an algebraic, unidirectional manner for multi-dimensional adaptations. The procedure is analogous to applying tension and torsion spring forces proportional to the local flow gradient at every grid point and finding the equilibrium position of the resulting system of grid points. The multi-dimensional problem of grid adaption is split into a series of one-dimensional problems along the computational coordinate lines. The reduced one dimensional problem then requires a tridiagonal solver to find the location of grid points along a coordinate line. Multi-directional adaption is achieved by the sequential application of the method in each coordinate direction. The tension forces direct the redistribution of points to the strong gradient region. To maintain smoothness and a measure of orthogonality of grid lines, torsional forces are introduced that relate information between the family of lines adjacent to one another. The smoothness and orthogonality constraints are direction-dependent, since they relate only the coordinate lines that are being adapted to the neighboring lines that have already been adapted. Therefore the solutions are non-unique and depend on the order and direction of adaption. Non-uniqueness of the adapted grid is

Differences of adaptation to school and self-resilience before and after sleep education for adolescent

OpenAIRE

Lee, So-Mi; Kim, Jong-Hee

2016-01-01

This study aims to verify the effectiveness of sleep education by identifying the differences of adaption to school and self-resilience of the high school students before and after sleep education for a certain period of time. The conclusion of this study is presented below: First, there were differences in adaptation to school and self-resilience of the high school students before and after sleep education for the high school students. After sleep education, adaptation to school environment ...

Unveiling adaptation using high-resolution lineage tracking

Science.gov (United States)

Blundell, Jamie; Levy, Sasha; Fisher, Daniel; Petrov, Dmitri; Sherlock, Gavin

2013-03-01

Human diseases such as cancer and microbial infections are adaptive processes inside the human body with enormous population sizes: between 106 -1012 cells. In spite of this our understanding of adaptation in large populations is limited. The key problem is the difficulty in identifying anything more than a handful of rare, large-effect beneficial mutations. The development and use of molecular barcodes allows us to uniquely tag hundreds of thousands of cells and enable us to track tens of thousands of adaptive mutations in large yeast populations. We use this system to test some of the key theories on which our understanding of adaptation in large populations is based. We (i) measure the fitness distribution in an evolving population at different times, (ii) identify when an appreciable fraction of clones in the population have at most a single adaptive mutation and isolate a large number of clones with independent single adaptive mutations, and (iii) use this clone collection to determine the distribution of fitness effects of single beneficial mutations.

Simulating the Emergence and Survival of Mutations Using a Self Regulating Multitype Branching Processes

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Charles J. Mode

2011-01-01

Full Text Available It is difficult for an experimenter to study the emergence and survival of mutations, because mutations are rare events so that large experimental population must be maintained to ensure a reasonable chance that a mutation will be observed. In his famous book, The Genetical Theory of Natural Selection, Sir R. A. Fisher introduced branching processes into evolutionary genetics as a framework for studying the emergence and survival of mutations in an evolving population. During the lifespan of Fisher, computer technology had not advanced to a point at which it became an effective tool for simulating the phenomenon of the emergence and survival of mutations, but given the wide availability of personal desktop and laptop computers, it is now possible and financially feasible for investigators to perform Monte Carlo Simulation experiments. In this paper all computer simulation experiments were carried out within a framework of self regulating multitype branching processes, which are part of a stochastic working paradigm. Emergence and survival of mutations could also be studied within a deterministic paradigm, which raises the issue as to what sense are predictions based on the stochastic and deterministic models are consistent. To come to grips with this issue, a technique was used such that a deterministic model could be embedded in a branching process so that the predictions of both the stochastic and deterministic compared based on the same assigned values of parameters.

The Effect of Coexistence of a Pair of Mutated Oncogenes on the Survival Rate of Invasive Breast Carcinoma Patients

Science.gov (United States)

Nair, D. R.

2017-12-01

The purpose of this project was to determine the effect of two mutated oncogenes on the survival rate from invasive breast carcinoma when in comparison to the mutation of a single oncogene on the survival rate. An oncogene is defined as a gene, that when mutated, can lead to cancer. The two oncogenes used in this project were human epidermal growth factor receptor 2 (HER2) and c-myc (MYC). HER2 and MYC are both oncogenes that contribute to the formation of cancer. HER2 proteins are receptors on breast cells, and when the HER2 gene is mutated, there is an overexpression of HER2 protein on the breast cell. This makes the breast cells proliferate uncontrollably. MYC is a gene that codes for a transcription factor that plays a role in cell cycle progression. The overexpression of MYC also leads to the proliferation of cells. I hypothesized that if there is a mutation in both the MYC and HER2 genes, then the survival rate of invasive breast carcinoma patients will be lower compared to patients with the mutations of only MYC or HER2. To test this hypothesis, we conducted individual gene searches in CBioPortal for HER2 in the datasets from the studies titled TCGA Nature 2012, TCGA Cell 2015, and TCGA Provisional. We conducted individual gene searches in CBioPortal for MYC in the same datasets. The survival rate data was then exported and analyzed for patients with mutations of either HER2 or MYC and with mutations of both genes. To determine the cases that had both HER2 and MYC mutations, we found the overlapping cases in both HER2 and MYC groups for all three datasets. We calculated the median of the survival data for cases where either HER2 or MYC was mutated and cases where both MYC and HER2 were mutated. From the first dataset, the median of MYC data was 95.53, HER2 data was 95.83, and both HER2 and MYC data was 91.24. In the second dataset, the median of MYC data was 92.17 , HER2 data was 93.5, and both HER2 and MYC data was 87.95 . In the third dataset, the median

Self-Adaptive On-Chip System Based on Cross-Layer Adaptation Approach

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Kais Loukil

2013-01-01

Full Text Available The emergence of mobile and battery operated multimedia systems and the diversity of supported applications mount new challenges in terms of design efficiency of these systems which must provide a maximum application quality of service (QoS in the presence of a dynamically varying environment. These optimization problems cannot be entirely solved at design time and some efficiency gains can be obtained at run-time by means of self-adaptivity. In this paper, we propose a new cross-layer hardware (HW/software (SW adaptation solution for embedded mobile systems. It supports application QoS under real-time and lifetime constraints via coordinated adaptation in the hardware, operating system (OS, and application layers. Our method relies on an original middleware solution used on both global and local managers. The global manager (GM handles large, long-term variations whereas the local manager (LM is used to guarantee real-time constraints. The GM acts in three layers whereas the LM acts in application and OS layers only. The main role of GM is to select the best configuration for each application to meet the constraints of the system and respect the preferences of the user. The proposed approach has been applied to a 3D graphics application and successfully implemented on an Altera FPGA.

Dimensions of self-rated health in older adults

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Flávia Silva Arbex Borim

2014-10-01

Full Text Available OBJECTIVE To analyze the association between negative self-rated health and indicators of health, wellbeing and sociodemographic variables in older adults. METHODS Cross-sectional study that used data from a population-based health survey with a probability cluster sample that was carried out in Campinas, SP, Southeastern Brazil,, in 2008 and 2009. The participants were older adults (≥ 60 years and the dependent variable was self-rated health, categorized as: excellent, very good, good, bad and very bad. The adjusted prevalence ratios were estimated by means of Poisson multiple regression. RESULTS The highest prevalences of bad/very bad self-rated health were observed in the individuals who never attended school, in those with lower level of schooling, with monthly per capita family income lower than one minimum salary. Individuals who scored five or more in the physical health indicator also had bad self-rated health, as well as those who scored five or more in the Self-Reporting Questionnaire 20 and those who did not refer feeling happiness all the time. CONCLUSIONS The independent effects of material life conditions, physical and mental health and subjective wellbeing, observed in self-rated health, suggest that older adults can benefit by health policies supported by a global and integrative view of old age.

Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

Science.gov (United States)

Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

2010-01-01

The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030

Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

Energy Technology Data Exchange (ETDEWEB)

Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

1996-08-09

Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

Functional annotation of the mesophilic-like character of mutants in a cold-adapted enzyme by self-organising map analysis of their molecular dynamics.

Science.gov (United States)

Fraccalvieri, Domenico; Tiberti, Matteo; Pandini, Alessandro; Bonati, Laura; Papaleo, Elena

2012-10-01

Multiple comparison of the Molecular Dynamics (MD) trajectories of mutants in a cold-adapted α-amylase (AHA) could be used to elucidate functional features required to restore mesophilic-like activity. Unfortunately it is challenging to identify the different dynamic behaviors and correctly relate them to functional activity by routine analysis. We here employed a previously developed and robust two-stage approach that combines Self-Organising Maps (SOMs) and hierarchical clustering to compare conformational ensembles of proteins. Moreover, we designed a novel strategy to identify the specific mutations that more efficiently convert the dynamic signature of the psychrophilic enzyme (AHA) to that of the mesophilic counterpart (PPA). The SOM trained on AHA and its variants was used to classify a PPA MD ensemble and successfully highlighted the relationships between the flexibilities of the target enzyme and of the different mutants. Moreover the local features of the mutants that mostly influence their global flexibility in a mesophilic-like direction were detected. It turns out that mutations of the cold-adapted enzyme to hydrophobic and aromatic residues are the most effective in restoring the PPA dynamic features and could guide the design of more mesophilic-like mutants. In conclusion, our strategy can efficiently extract specific dynamic signatures related to function from multiple comparisons of MD conformational ensembles. Therefore, it can be a promising tool for protein engineering.

Adolescent Girls' Self-Concept and Its Related Factors Based on Roy Adaptation Model

OpenAIRE

M. Basiri Moghadam; SH. Khosravan; L. Sadeghmoghadam; N. Ebrahimi Senoo

2017-01-01

Aims: One of the most important factors of individual health in the adolescents is the self-concept. As a nursing model, the Roy adaptation model mainly investigates the factor. The aim of the study was to investigate the self-concept and its related factors in the adolescent girls in Gonabad Township, based on the Roy adaptation model. Instrument & Methods: In the descriptive cross-sectional study, 270 adolescent girls were studied in Gonabad Township, Iran, in 2015. The subjects were s...

Adaptive Backstepping Self-balancing Control of a Two-wheel Electric Scooter

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Nguyen Ngoc Son

2014-10-01

Full Text Available This paper introduces an adaptive backstepping control law for a two-wheel electric scooter (eScooter with a nonlinear uncertain model. Adaptive backstepping control is integrated with feedback control that satisfies Lyapunov stability. By using the recursive structure to find the controlled function and estimate uncertain parameters, an adaptive backstepping method allows us to build a feedback control law that efficiently controls a self-balancing controller of the eScooter. Additionally, a controller area network (CAN bus with high reliability is applied for communicating between the modules of the eScooter. Simulation and experimental results demonstrate the robustness and good performance of the proposed adaptive backstepping control.

An Efficient and Self-Adapting Localization in Static Wireless Sensor Networks

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Wei Dong

2009-08-01

Full Text Available Localization is one of the most important subjects in Wireless Sensor Networks (WSNs. To reduce the number of beacons and adopt probabilistic methods, some particle filter-based mobile beacon-assisted localization approaches have been proposed, such as Mobile Beacon-assisted Localization (MBL, Adapting MBL (A-MBL, and the method proposed by Hang et al. Some new significant problems arise in these approaches, however. The first question is which probability distribution should be selected as the dynamic model in the prediction stage. The second is whether the unknown node adopts neighbors’ observation in the update stage. The third is how to find a self-adapting mechanism to achieve more flexibility in the adapting stage. In this paper, we give the theoretical analysis and experimental evaluations to suggest which probability distribution in the dynamic model should be adopted to improve the efficiency in the prediction stage. We also give the condition for whether the unknown node should use the observations from its neighbors to improve the accuracy. Finally, we propose a Self-Adapting Mobile Beacon-assisted Localization (SA-MBL approach to achieve more flexibility and achieve almost the same performance with A-MBL.

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving s......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

Self-adapted sliding scale spectroscopy ADC

International Nuclear Information System (INIS)

Xu Qichun; Wang Jingjin

1992-01-01

The traditional sliding scale technique causes a disabled range that is equal to the sliding length, thus reduces the analysis range of a MCA. A method for reduce ADC's DNL, which is called self-adapted sliding scale method, has been designed and tested. With this method, the disabled range caused by a traditional sliding scale method can be eliminated by a random trial scale and there is no need of an additional amplitude discriminator with swing threshold. A special trial-and-correct logic is presented. The tested DNL of the spectroscopy ADC described here is less than 0.5%

Finite element method for solving Kohn-Sham equations based on self-adaptive tetrahedral mesh

International Nuclear Information System (INIS)

Zhang Dier; Shen Lihua; Zhou Aihui; Gong Xingao

2008-01-01

A finite element (FE) method with self-adaptive mesh-refinement technique is developed for solving the density functional Kohn-Sham equations. The FE method adopts local piecewise polynomials basis functions, which produces sparsely structured matrices of Hamiltonian. The method is well suitable for parallel implementation without using Fourier transform. In addition, the self-adaptive mesh-refinement technique can control the computational accuracy and efficiency with optimal mesh density in different regions

Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers

DEFF Research Database (Denmark)

Eskildsen, Simon F; Østergaard, Lasse R; Rodell, Anders B

2008-01-01

with a mean interval of 16 months and surface based cortical segmentation we measured cortical thickness and volume, and quantified atrophy rates. Cortical thickness and atrophy rates were averaged within major lobes and focal effects were determined by parametric statistical maps. The volumetric atrophy...... in the frontal and occipital lobes, and in the left temporal lobe. Results indicated that cortical thickness has a higher sensitivity for detecting small changes than whole-brain volumetric measures. Comparing mutation carriers with non-carriers revealed increased atrophy rates in mutation carriers bilaterally...

Adaptive change in self-concept and well-being during conjugal loss in later life.

Science.gov (United States)

Montpetit, Mignon A; Bergeman, C S; Bisconti, Toni L; Rausch, Joseph R

2006-01-01

The present study examines the association between the self-concept and adaptation to conjugal loss; the primary aim was to explore whether those individuals high in self-esteem, environmental mastery, and optimism have more adaptive resources with which to ameliorate the detrimental sequelae of bereavement. Analyses were conducted on data collected from 58 widows every four months over a two-year period. One goal of the research was to explore the adequacy of the theoretically chosen operational definition of the self-concept; another goal was to analyze how changes in the level of self-concept components correlated with changes in levels of depression, health, and grief resolution as individuals adjusted to their losses. Analyses revealed that trajectories of depression and grief resolution were more highly related than health to changes in self-concept.

Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages

Science.gov (United States)

Vieira, Marcos C; Zinder, Daniel; Cobey, Sarah

2018-01-01

Abstract High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable “hotspot” motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza. PMID:29688540

Correlation of mycelial growth rate with other characters in evolved genotypes of Aspergillus nidulans

NARCIS (Netherlands)

Schoustra, S.E.; Punzalan, D.

2012-01-01

Fungal populations can adapt to their environment by the generation and fixation of spontaneous beneficial mutations. In this study we examined whether adaptation, measured as an increased mycelial growth rate, has correlated responses in the filamentous fungus Aspergillus nidulans with several

Erratum Haldane and the first estimates of the human mutation rate

Indian Academy of Sciences (India)

Published on the Web: 1 December 2008. Erratum. Haldane and the first estimates of the human mutation rate. (A commentary on J.B.S. Haldane 1935 J. Genet. 31, 317–326; reprinted in volume 83, 235–244 as a J. Genet. classic). Michael W. Nachman. J. Genet. 83, 231–233. Page 1, right column, para 1, line 6 from ...

Cross-cultural Adaptation of the Self-care of Hypertension Inventory Into Brazilian Portuguese.

Science.gov (United States)

Silveira, Luana Claudia Jacoby; Rabelo-Silva, Eneida Rejane; Ávila, Christiane Whast; Beltrami Moreira, Leila; Dickson, Victoria Vaughan; Riegel, Barbara

Lifestyle changes and treatment adherence still constitute a challenge to healthcare providers involved in the care of persons with hypertension. The lack of validated instruments measuring the ability of hypertensive patients to manage their disease has slowed research progress in this area. The Self-care of Hypertension Inventory, originally developed in the United States, consists of 23 items divided across 3 scales: Self-care Maintenance, Self-care Management, and Self-care Confidence. These scales measure how well patients with hypertension adhere to treatment and manage elevated blood pressure, as well as their confidence in their ability to perform self-care. A rigorous cross-cultural adaptation and validation process is required before this instrument can be used in other countries. The aims of this study were to translate the Self-care of Hypertension Inventory into Brazilian Portuguese with cross-cultural adaptation and to evaluate interobserver reliability and temporal stability. This methodological study involved forward translation, synthesis of forward translations, back-translation, synthesis of back-translations, expert committee review, and pretesting. Interobserver agreement and the temporal stability of the scales were assessed. The expert committee proposed semantic and cultural modifications to some items and the addition of guidance statements to facilitate administration of the scale. Interobserver analysis demonstrated substantial agreement. Analysis of temporal stability showed near-perfect agreement. Cross-cultural adaptation of the Self-care of Hypertension Inventory successfully produced a Portuguese-language version of the instrument for further evaluation of psychometric properties. Once that step is completed, the scale can be used in Brazil.

The study of human mutation rates

International Nuclear Information System (INIS)

Neel, J.V.

1992-01-01

We will describe recent developments regarding the question of induced mutations in the survivors of the atomic bombings of Hiroshima and Nagasaki. As part of that work we, describe some developments with respect to the Amerindian blood samples collected under DoE sponsorship between 1964 and 1982. Then developments regarding the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to the study of genetic variation and mutation affecting protein characteristics. In particular, we will report on the identification and isolation of genes of especial interest as reflected in the behavior of the proteins which they encode

Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia.

Science.gov (United States)

Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela; Wong, Wesley; Daniels, Rachel; Demas, Allison; Schaffner, Stephen; Amaratunga, Chanaki; Lim, Pharath; Dhorda, Mehul; Miotto, Olivo; Woodrow, Charles; Ashley, Elizabeth A; Dondorp, Arjen M; White, Nicholas J; Wirth, Dyann; Fairhurst, Rick; Volkman, Sarah K

2017-05-12

Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance. Sixty-eight parasites isolates with in vivo clearance data were obtained from two Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture-adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy number; and the RSA 0-3h survival rates and response to antimalarial drugs in vitro were measured for 36 of these isolates. Among these 36 parasites one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation (D584V, RSA 0-3h  = 8%), previously associated with slow clearance but not yet tested in vitro. Several parasites exhibited increased ring-stage survival, yet lack pfkelch13 mutations, and one isolate showed evidence for piperaquine resistance. This study of 68 culture-adapted Plasmodium falciparum clinical isolates from Cambodia with known clearance values, associated the D584V PfKelch13 mutation with increased ring-stage survival and identified parasites that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These data suggest mutations other than those found in pfkelch13 may be involved in conferring artemisinin resistance in P. falciparum. Piperaquine resistance was also detected among the same Cambodian samples, consistent with reports of emerging piperaquine resistance in the field. These culture-adapted parasites permit further investigation of mechanisms of both artemisinin and piperaquine

mHealth intervention to support asthma self-management in adolescents: the ADAPT study

Directory of Open Access Journals (Sweden)

Kosse RC

2017-03-01

Full Text Available Richelle C Kosse,1 Marcel L Bouvy,1 Tjalling W de Vries,2 Ad A Kaptein,3 Harm CJ Geers,1 Liset van Dijk,4 Ellen S Koster1 1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, 2Department of Paediatrics, Medical Center Leeuwarden, Leeuwarden, 3Medical Psychology, Leiden University Medical Center, Leiden, 4NIVEL, the Netherlands Institute for Health Services Research, Utrecht, the Netherlands Purpose: Poor medication adherence in adolescents with asthma results in poorly controlled disease and increased morbidity. The aim of the ADolescent Adherence Patient Tool (ADAPT study is to develop an mHealth intervention to support self-management and to evaluate the effectiveness in improving medication adherence and asthma control. Intervention: The ADAPT intervention consists of an interactive smartphone application (app connected to a desktop application for health care providers, in this study, the community pharmacist. The app contains several functions to improve adherence as follows: 1 a questionnaire function to rate asthma symptoms and monitor these over time; 2 short movie clips with medication and disease information; 3 a medication reminder; 4 a chat function with peers; and 5 a chat function with the pharmacist. The pharmacist receives data from the patient’s app through the desktop application, which enables the pharmacist to send information and feedback to the patient. Study design: The ADAPT intervention is tested in a community pharmacy-based cluster randomized controlled trial in the Netherlands, aiming to include 352 adolescents with asthma. The main outcome is adherence, measured by patient’s self-report and refill adherence calculated from pharmacy dispensing records. In addition, asthma control, illness perceptions, medication beliefs, and asthma-related quality of life are measured. Conclusion: This study will provide in

Self-adaptive demodulation for polarization extinction ratio in distributed polarization coupling.

Science.gov (United States)

Zhang, Hongxia; Ren, Yaguang; Liu, Tiegen; Jia, Dagong; Zhang, Yimo

2013-06-20

A self-adaptive method for distributed polarization extinction ratio (PER) demodulation is demonstrated. It is characterized by dynamic PER threshold coupling intensity (TCI) and nonuniform PER iteration step length (ISL). Based on the preset PER calculation accuracy and original distribution coupling intensity, TCI and ISL can be made self-adaptive to determine contributing coupling points inside the polarizing devices. Distributed PER is calculated by accumulating those coupling points automatically and selectively. Two different kinds of polarization-maintaining fibers are tested, and PERs are obtained after merely 3-5 iterations using the proposed method. Comparison experiments with Thorlabs commercial instrument are also conducted, and results show high consistency. In addition, the optimum preset PER calculation accuracy of 0.05 dB is obtained through many repeated experiments.

Age and sex effects on human mutation rates. An old problem with new complexities

International Nuclear Information System (INIS)

Crow, James F.

2006-01-01

Base substitution mutations are far more common in human males than in females, and the frequency increases with paternal age. Both can be accounted for by the greater number of pre-meiotic cell divisions in males, especially old ones. In contrast, small deletions do not show any important age effect and occur with approximately equal frequency in the two sexes. Mutations in most genes include both types, and the sex and paternal age effect depends on the proportion of the two types. A few traits, of which Apert Syndrome is best understood, are mutation hot spots with all the mutations occurring in one or two codons, usually at one nucleotide. They occur with very high frequency almost exclusively in males and the frequency increases rapidly with paternal age. It has been suggested that the mutant cells have a selective advantage in the male germ-line prior to meiosis. Evidence for this surprising, but important, hypothesis is discussed. A possible mechanism is the conversion of asymmetrical stem-cell divisions into symmetric ones. Some traits with complex etiology show a slight paternal age effect. There is also a short discussion of the high deleterious mutation rate and the role of sexual reproduction in reducing the consequent mutation load. (author)

The relationships of social support, uncertainty, self-efficacy, and commitment to prenatal psychosocial adaptation.

Science.gov (United States)

Hui Choi, W H; Lee, G L; Chan, Celia H Y; Cheung, Ray Y H; Lee, Irene L Y; Chan, Cecilia L W

2012-12-01

To report a study of the relations of prenatal psychosocial adaptation, social support, demographic and obstetric characteristics, uncertainty, information-seeking behaviour, motherhood normalization, self-efficacy, and commitment to pregnancy. Prenatal psychosocial assessment is recommended to identify psychosocial risk factors early to prevent psychiatric morbidities of mothers and children. However, knowledge on psychosocial adaptation and its explanatory variables is inconclusive. This study was non-experimental, with a cross-sectional, correlational, prospective design. The study investigated Hong Kong Chinese women during late pregnancy. Convenience sampling methods were used, with 550 women recruited from the low-risk clinics of three public hospitals. Data was collected between January-April 2007. A self-reported questionnaire was used, consisting of a number of measurements derived from an integrated framework of the Life Transition Theory and Theory of Uncertainty in Illness. Explanatory variables of psychosocial adaptation were identified using a structural equation modelling programme. The four explanatory variables of the psychosocial adaptation were social support, uncertainty, self-efficacy, and commitment to pregnancy. In the established model, which had good fit indices, greater psychosocial adaptation was associated with higher social support, higher self-efficacy, higher commitment to pregnancy, and lower uncertainty. The findings give clinicians and midwives guidance in the aspects to focus on when providing psychosocial assessment in routine prenatal screening. Since there are insufficient reliable screening tools to assist that assessment, midwives should receive adequate training, and effective screening instruments have to be identified. The explanatory role of uncertainty found in this study should encourage inquiries into the relationship between uncertainty and psychosocial adaptation in pregnancy. © 2012 Blackwell Publishing Ltd.

The association between physical activity, cardiorespiratory fitness and self-rated health

DEFF Research Database (Denmark)

Eriksen, Louise; Curtis, Tine; Grønbæk, Morten

2013-01-01

OBJECTIVE: To investigate the joint association between self-reported physical activity as well as cardiorespiratory fitness and self-rated health among healthy women and men. METHOD: Data from 10,416 participants in The Danish Health Examination Survey 2007-2008 which took part in 13 Danish...... municipalities were analyzed. Leisure time physical activity level and self-rated health were based on self-reported questionnaire data. Optimal self-rated health was defined as "very good" or "good" self-rated health. Cardiorespiratory fitness (mL O2·min(-1)·kg(-1)) was estimated from maximal power output...... in a maximal cycle exercise test. RESULTS: A strong dose-response relation between cardiorespiratory fitness and self-rated health as well as between physical activity level and self-rated health among both women and men was found. Within categories of physical activity, odds ratios for optimal self...

Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients

DEFF Research Database (Denmark)

Vahlquist, Anders; Bygum, Anette; Gånemo, Agneta

2010-01-01

Infants born with autosomal recessive congenital ichthyosis (ARCI) are often encapsulated in a collodion membrane, which shows a lamellar or erythrodermic type of ichthyosis upon shedding. However, some babies show a nearly normal underlying skin after several weeks, a phenotype called "self...... scaling, palmar hyperlinearity with keratoderma, and a frequent appearance of red cheeks and anhidrosis. Thus, we propose replacing SHCB with the term "self-improving collodion ichthyosis" (SICI). In conclusion, ALOX12B mutations are the leading cause of SICI in Scandinavia, followed by ALOXE3 mutations...

Genotypic and Clinical Spectrum of Self-Improving Collodion Ichthyosis: ALOX12B, ALOXE3, and TGM1 Mutations in Scandinavian Patients

DEFF Research Database (Denmark)

Vahlquist, Anders; Bygum, Anette; Gånemo, Agneta

2009-01-01

Infants born with autosomal recessive congenital ichthyosis (ARCI) are often encapsulated in a collodion membrane, which shows a lamellar or erythrodermic type of ichthyosis upon shedding. However, some babies show a nearly normal underlying skin after several weeks, a phenotype called "self...... scaling, palmar hyperlinearity with keratoderma, and a frequent appearance of red cheeks and anhidrosis. Thus, we propose replacing SHCB with the term "self-improving collodion ichthyosis" (SICI). In conclusion, ALOX12B mutations are the leading cause of SICI in Scandinavia, followed by ALOXE3 mutations...

Adaptation of Self-Control and Self-Management Scale (SCMS) into Turkish Culture: A Study on Reliability and Validity

Science.gov (United States)

Ercoskun, Muhammet Hanifi

2016-01-01

The aim of this study is to adapt self-control and self-management scale (SCMS) developed by Mezo into Turkish and to test it considering gender and academic achievement variables. The scale was translated from English to Turkish for linguistic validity and then this scale was translated into English using back translation. The original and…

Genetic polymorphisms and mutation rates of 27 Y-chromosomal STRs in a Han population from Guangdong Province, Southern China.

Science.gov (United States)

Wang, Ying; Zhang, Yong-Ji; Zhang, Chu-chu; Li, Ran; Yang, Yang; Ou, Xue-Ling; Tong, Da-yue; Sun, Hong-Yu

2016-03-01

In this study, we collected blood samples from 1033 father-son pairs of a Han population from Guangdong Province, Southern China, of which 1007 fathers were unrelated male individuals. All together, 2040 male individuals were analyzed at 27 Y-chromosomal short tandem repeats (Y-STRs) with Yfiler(®) Plus system. A total of 1003 different haplotypes were observed among 1007 unrelated fathers, with the overall haplotype diversity (HD) 0.999992 and discrimination capacity (DC) 0.996. The gene diversity (GD) values for the 27 Y-STR loci ranged from 0.4400 at DYS438 to 0.9597 at DYS385a/b. 11 off-ladder alleles and 25 copy number variants were detected in 1007 males. Population relationships were analyzed by comparison with 19 other worldwide populations. With 27,920 allele transfers in 1033 father-son pairs, 124 mutation events occurred, of which 118 were one-step mutations and 6 were two-step mutations. Eleven father-son pairs were found to have mutations at two loci, while one pair at three loci. The estimated locus-specific mutation rates varied from 0 to 1.74×10(-2), with an average estimated mutation rate 4.4×10(-3) (95%CI: 3.7×10(-3) to 5.3×10(-3)). Mutations were most frequently observed at three rapidly mutating Y-STRs (RM Y-STRs), DYS576, DYS518 and DYS627. However, at DYS570, DYS449 and DYF387S1 loci, which were also described as RM Y-STRs, the mutation rates in Guangdong Han population were not as high as estimated in other populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pathoadaptation of a Human Pathogen Through Non-Coding Intergenic Mutations

DEFF Research Database (Denmark)

Khademi, Seyed Mohammad Hossein

in CF adaptation of P. aeruginosa and their expressions are altered by the mutation. It was established that mutations upstream ampR increased tolerance of P. aeruginosa to some β-lactam antibiotics. Mutations in promoter of phuR, encoding receptor of pseudomonas heme uptake system, conferred growth...... advantage in the presence of hemoglobin demonstrating that P. aeruginosa has adapted towards utilization of iron from hemoglobin. Further investigation of phuR promoter mutation revealed pleiotropic effects on expression of many other genes. The pleiotropic effect by this mutation was contingent...

Population data and mutation rates of 19 STR loci in seven provinces from China based on Goldeneye™ DNA ID System 20A.

Science.gov (United States)

Liu, Qiu-Ling; Chen, Ye-Fei; Huang, Xiao-Ling; Liu, Kai-Yan; Zhao, Hu; Lu, De-Jian

2017-05-01

Short tandem repeat (STR) analysis is a primary tool in forensic casework. Population data and mutation rates of STRs are very important for paternity testing and forensic genetics. However, the population data and mutation rates of STRs in Han nationality based on large samples have still not been fully described in China. In this study, the allelic frequencies, forensic parameters, and mutation rate of 19 STR loci (D19S433, D5S818, D21S11, D18S51, D6S1043, D3S1358, D13S317, D7S820, D16S539, CSFIPO, PentaD, vWA, D8S1179, TPOX, Penta E, TH01, D12S391, D2S1338, and FGA) based on the Goldeneye™ DNA ID System 20A in Southern China Han nationality among seven provinces were investigated. Furthermore, population stratification of Southern China Han nationality among seven provinces was established. The multidimensional scaling (MDS) plot based on genetic distances (Fst) showed that the studied populations can be clustered into two major groups. However, relationships among populations were weak (Fst < 0.0043). A total of 376 cases of mutation were detected from the 19 selected loci in 15,396 meioses. The average mutation rate for the 19 loci was estimated to be 1.3 × 10 -3 per meiosis. The mutation was mainly single step; the paternal mutation rate was higher than the maternal; and paternal mutation rate increases with paternal age.

Self-adapting the success rate when practicing math

NARCIS (Netherlands)

Jansen, B.R.J.; Hofman, A.D.; Savi, A.; Visser, I.; van der Maas, H.L.J.

2016-01-01

Use and benefits of the possibility to choose a success rate are studied in a math-practice application that is used by a considerable percentage of Dutch primary school children. Study 1 uses data that were collected with the application, using children's practice data (N = 40,329; grades 1–6).

Are adaptations self-organized, autonomous, and harmonious? Assessing the social-ecological resilience literature

Directory of Open Access Journals (Sweden)

Thomas Hahn

2017-03-01

Full Text Available The paper analyzes how adaptability (adaptive capacity and adaptations is constructed in the literature on resilience of social-ecological systems (SES. According to some critics, this literature views adaptability as the capacity of SES to self-organize in an autonomous harmonious consensus-building process, ignoring strategies, conflicting goals, and power issues. We assessed 183 papers, coding two dimensions of adaptability: autonomous vs. intentional and descriptive vs. normative. We found a plurality of framings, where 51% of the papers perceived adaptability as autonomous, but one-third constructed adaptability as intentional processes driven by stakeholders; where social learning and networking are often used as strategies for changing power structures and achieving sustainability transformations. For the other dimension, adaptability was used normatively in 59% of the assessed papers, but one-third used descriptive framings. We found no evidence that the SES literature in general assumes a priori that adaptations are harmonious consensus-building processes. It is, rather, conflicts that are assumed, not spelled out, and assertions of "desirable" that are often not clarified by reference to policy documents or explicit normative frameworks. We discuss alternative definitions of adaptability and transformability to clarify or avoid the notion of desirability. Complex adaptive systems framing often precludes analysis of agency, but lately self-organization and emergence have been used to study actors with intentions, strategies, and conflicting interests. Transformations and power structures are increasingly being addressed in the SES literature. We conclude that ontological clashes between social science and SES research have resulted in multiple constructive pathways.

Self-adapting metal-ceramic coating for biomass and waste incineration plants

Energy Technology Data Exchange (ETDEWEB)

Faulstich, Martin [Technische Univ. Muenchen (Germany); Fehr, Karl Thomas; Ye, Ya-Ping [Ludwig-Maximilians-Univ., Muenchen (Germany); Loeh, Ingrid; Mocker, Mario; Wolf, Gerhard [ATZ Entwicklungszentrum, Sulzbach-Rosenberg (Germany)

2010-07-01

Thermally sprayed coatings might become a reasonable alternative to cost-intensive cladding of heat exchangers in biomass and waste incineration. Shortcomings of these coatings might be overcome by a double-layer system, consisting of Alloy 625 covered with yttria-stabilized zirconia. Under appropriate conditions, re-crystallized zirconium oxide and chromium oxide form a dense, self-adapting and self-healing barrier against further infiltration of gaseous species. (orig.)

Prediction of adaptive self-regulatory responses to arthritis pain anxiety in exercising adults: does pain acceptance matter?

Science.gov (United States)

Cary, Miranda Ashley; Gyurcsik, Nancy C; Brawley, Lawrence R

2015-01-01

Exercising for ≥ 150 min/week is a recommended strategy for self-managing arthritis. However, exercise nonadherence is a problem. Arthritis pain anxiety may interfere with regular exercise. According to the fear-avoidance model, individuals may confront their pain anxiety by using adaptive self-regulatory responses (eg, changing exercise type or duration). Furthermore, the anxiety-self-regulatory responses relationship may vary as a function of individuals' pain acceptance levels. To investigate pain acceptance as a moderator of the pain anxiety-adaptive self-regulatory responses relationship. The secondary objective was to examine whether groups of patients who differed in meeting exercise recommendations also differed in pain-related and self-regulatory responses. Adults (mean [± SD] age 49.75 ± 13.88 years) with medically diagnosed arthritis completed online measures of arthritis pain-related variables and self-regulatory responses at baseline, and exercise participation two weeks later. Individuals meeting (n=87) and not meeting (n=49) exercise recommendations were identified. Hierarchical multiple regression analysis revealed that pain acceptance moderated the anxiety-adaptive self-regulatory responses relationship. When pain anxiety was lower, greater pain acceptance was associated with less frequent use of adaptive responses. When anxiety was higher, adaptive responses were used regardless of pain acceptance level. MANOVA findings revealed that participants meeting the recommended exercise dose reported significantly lower pain and pain anxiety, and greater pain acceptance (Pself-regulatory capacity to cope with additional challenges to exercise adherence (eg, busy schedule).

The association between physical activity, cardiorespiratory fitness and self-rated health.

Science.gov (United States)

Eriksen, Louise; Curtis, Tine; Grønbæk, Morten; Helge, Jørn W; Tolstrup, Janne S

2013-12-01

To investigate the joint association between self-reported physical activity as well as cardiorespiratory fitness and self-rated health among healthy women and men. Data from 10,416 participants in The Danish Health Examination Survey 2007-2008 which took part in 13 Danish municipalities were analyzed. Leisure time physical activity level and self-rated health were based on self-reported questionnaire data. Optimal self-rated health was defined as "very good" or "good" self-rated health. Cardiorespiratory fitness (mL O2·min(-1)·kg(-1)) was estimated from maximal power output in a maximal cycle exercise test. A strong dose-response relation between cardiorespiratory fitness and self-rated health as well as between physical activity level and self-rated health among both women and men was found. Within categories of physical activity, odds ratios for optimal self-rated health increased with increasing categories of cardiorespiratory fitness, and vice versa. Hence, participants who were moderately/vigorously physically active and had a high cardiorespiratory fitness had the highest odds ratio for optimal self-rated health compared with sedentary participants with low cardiorespiratory fitness (odds ratio=12.2, 95% confidence interval: 9.3-16.1). Although reluctant to conclude on causality, this study suggests that an active lifestyle as well as good cardiorespiratory fitness probably increase self-rated health. © 2013.

Teachers' Definitions of Self-Esteem When Rating Preschool Children.

Science.gov (United States)

Bell, Nancy J.; And Others

1980-01-01

Female teachers rated 107 preschool boys and girls on their self-esteem and on a sex role rating scale. Although the validity of such ratings remains an issue, it appears that children rated high in self-esteem by their teachers are those perceived as assertive, active, athletic--stereotypically masculine traits. (Author/SJL)

Social capital and self-rated health among older Korean immigrants.

Science.gov (United States)

Kim, Bum Jung; Harris, Lesley Maradik

2013-12-01

The objective of this article is to investigate determinants of self-rated health and describe their association with social capital and socioeconomic characteristics among older Korean immigrants. A cross-sectional study of 205 older Korean immigrants (aged 60 years and older) was conducted in Los Angeles county. Independent variables included age, gender, marital status, income of the older Koreans, and social capital included social norms, trust, partnership with the community, information sharing, and political participation. Self-rated health was the dependent variable. Descriptive analyses were done to show group differences in self-rated health and logistic regression analyses to identify determinants of self-rated health. Gender (male), high income, and high levels of information sharing were significant determinants of high self-rated health status among older Korean immigrants. This population-based study provides empirical evidence that gender, income, and information sharing are directly associated with the self-rated health status of older Korean immigrants.

A single-rate context-dependent learning process underlies rapid adaptation to familiar object dynamics.

Science.gov (United States)

Ingram, James N; Howard, Ian S; Flanagan, J Randall; Wolpert, Daniel M

2011-09-01

Motor learning has been extensively studied using dynamic (force-field) perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple-context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar object dynamics

A single-rate context-dependent learning process underlies rapid adaptation to familiar object dynamics.

Directory of Open Access Journals (Sweden)

James N Ingram

2011-09-01

Full Text Available Motor learning has been extensively studied using dynamic (force-field perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple-context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar

Study on the pressure self-adaptive water-tight junction box in underwater vehicle

Directory of Open Access Journals (Sweden)

Haocai Huang

2012-09-01

Full Text Available Underwater vehicles play a very important role in underwater engineering. Water-tight junction box (WJB is one of the key components in underwater vehicle. This paper puts forward a pressure self-adaptive water-tight junction box (PSAWJB which improves the reliability of the WJB significantly by solving the sealing and pressure problems in conventional WJB design. By redundancy design method, the pressure self-adaptive equalizer (PSAE is designed in such a way that it consists of a piston pressure-adaptive compensator (PPAC and a titanium film pressure-adaptive compensator (TFPAC. According to hydro-mechanical simulations, the operating volume of the PSAE is more than or equal to 11.6 % of the volume of WJB liquid system. Furthermore, the required operating volume of the PSAE also increases as the gas content of oil, hydrostatic pressure or temperature difference increases. The reliability of the PSAWJB is proved by hyperbaric chamber tests.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process

OpenAIRE

Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

2015-01-01

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution e...

Development of the Self-Esteem Rating Scale for Children (Revised).

Science.gov (United States)

Chiu, Lian-Hwang

1987-01-01

Developed a teacher's rating scale of self-esteem for children. Participants were 231 school children in grades K-7. Used sociometric measures, popularity ranking by teachers, and the Coopersmith Self-Esteem Inventory to estimate validity. The Self-Esteem Rating Scale for Children (SERSC) included 12 behavioral characteristics rated most…

Adaptive self-correcting control system

International Nuclear Information System (INIS)

Ellis, S.H.

1984-01-01

A control system for regulating a controlled device or process, such as a turbofan engine, produces independent multiple estimates of one or more controlled variables of the device or process by combining the signals from a plurality of feedback sensors, which provide information related to the controlled variables, in weighted nonordered pairs. The independent multiple estimates of each controlled variable are combined into a weighted average, and individual estimates which differ by more than a specified amount from the weighted average are edited and temporarily removed from consideration. A revised weighted average value of each controlled variable is then produced, and this value is used to limit or control operation of the device or process. Adaptive trim is provided to compensate for changes in the device or process being controlled, such as engine deterioration, by slowly trimming each individual estimate toward the mean, and includes error compensation which constrains the weighted sum of the adaptive trims to equal zero, thereby preventing the adaptive trim from changing the operating level of the device or process. A secondary editing circuit based on a majority rule principle identifies a failed feedback sensor and permanently excludes all individual estimates of the controlled variable based on the failed sensor. Editing boundaries are increased and adaptive trim rate is varied when a transient occurs in the operation of the device or process. Further transient compensation may be required for a system with more severe transient requirements, and this invention includes compensation to selected feedback parameters such as turbine temperature to account for differences between steady state and transient values

Prospective evaluation of psychosocial adaptation to stoma surgery: the role of self-efficacy.

NARCIS (Netherlands)

Bekkers, M.J.T.; Knippenberg, F.C.E. van; Borne, H.W. van den; Berge-Henegouwen, G.P. van

1996-01-01

Self-efficacy, one's expectations regarding the ability to perform some specific task, was studied prospectively in the adaptation process of stoma patients. One week after surgery, stoma-related self-efficacy was assessed in 59 patients (26 cancer patients and 33 patients with benign diseases) who

Adaptive Convergence Rates of a Dirichlet Process Mixture of Multivariate Normals

OpenAIRE

Tokdar, Surya T.

2011-01-01

It is shown that a simple Dirichlet process mixture of multivariate normals offers Bayesian density estimation with adaptive posterior convergence rates. Toward this, a novel sieve for non-parametric mixture densities is explored, and its rate adaptability to various smoothness classes of densities in arbitrary dimension is demonstrated. This sieve construction is expected to offer a substantial technical advancement in studying Bayesian non-parametric mixture models based on stick-breaking p...

The Rate and Spectrum of Spontaneous Mutations in Mycobacterium smegmatis, a Bacterium Naturally Devoid of the Postreplicative Mismatch Repair Pathway.

Science.gov (United States)

Kucukyildirim, Sibel; Long, Hongan; Sung, Way; Miller, Samuel F; Doak, Thomas G; Lynch, Michael

2016-07-07

Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR) homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 × 10(-10) per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms. Transitions were found more frequently than transversions, with the A:T→G:C transition rate significantly higher than the G:C→A:T transition rate, opposite to what is observed in most studied bacteria. We also found that the transition-mutation rate of M. smegmatis is significantly lower than that of other naturally MMR-devoid or MMR-knockout organisms. Two possible candidates that could be responsible for maintaining high DNA fidelity in this MMR-deficient organism are the ancestral-like DNA polymerase DnaE1, which contains a highly efficient DNA proofreading histidinol phosphatase (PHP) domain, and/or the existence of a uracil-DNA glycosylase B (UdgB) homolog that might protect the GC-rich M. smegmatis genome against DNA damage arising from oxidation or deamination. Our results suggest that M. smegmatis has a noncanonical Dam (DNA adenine methylase) methylation system, with target motifs differing from those previously reported. The mutation features of M. smegmatis provide further evidence that genomes harbor alternative routes for improving replication fidelity, even in the absence of major repair pathways. Copyright © 2016 Kucukyildirim et al.

The Rate and Spectrum of Spontaneous Mutations in Mycobacterium smegmatis, a Bacterium Naturally Devoid of the Postreplicative Mismatch Repair Pathway

Directory of Open Access Journals (Sweden)

Sibel Kucukyildirim

2016-07-01

Full Text Available Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 × 10−10 per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms. Transitions were found more frequently than transversions, with the A:T→G:C transition rate significantly higher than the G:C→A:T transition rate, opposite to what is observed in most studied bacteria. We also found that the transition-mutation rate of M. smegmatis is significantly lower than that of other naturally MMR-devoid or MMR-knockout organisms. Two possible candidates that could be responsible for maintaining high DNA fidelity in this MMR-deficient organism are the ancestral-like DNA polymerase DnaE1, which contains a highly efficient DNA proofreading histidinol phosphatase (PHP domain, and/or the existence of a uracil-DNA glycosylase B (UdgB homolog that might protect the GC-rich M. smegmatis genome against DNA damage arising from oxidation or deamination. Our results suggest that M. smegmatis has a noncanonical Dam (DNA adenine methylase methylation system, with target motifs differing from those previously reported. The mutation features of M. smegmatis provide further evidence that genomes harbor alternative routes for improving replication fidelity, even in the absence of major repair pathways.

Goal orientation and work role performance: predicting adaptive and proactive work role performance through self-leadership strategies.

Science.gov (United States)

Marques-Quinteiro, Pedro; Curral, Luís Alberto

2012-01-01

This article explores the relationship between goal orientation, self-leadership dimensions, and adaptive and proactive work role performances. The authors hypothesize that learning orientation, in contrast to performance orientation, positively predicts proactive and adaptive work role performances and that this relationship is mediated by self-leadership behavior-focused strategies. It is posited that self-leadership natural reward strategies and thought pattern strategies are expected to moderate this relationship. Workers (N = 108) from a software company participated in this study. As expected, learning orientation did predict adaptive and proactive work role performance. Moreover, in the relationship between learning orientation and proactive work role performance through self-leadership behavior-focused strategies, a moderated mediation effect was found for self-leadership natural reward and thought pattern strategies. In the end, the authors discuss the results and implications are discussed and future research directions are proposed.

Self-serving bias effects on job analysis ratings.

Science.gov (United States)

Cucina, Jeffrey M; Martin, Nicholas R; Vasilopoulos, Nicholas L; Thibodeuax, Henry F

2012-01-01

The purpose of this study was to investigate whether worker-oriented job analysis importance ratings were influenced by subject matter experts' (SME) standing (as measured by self-rated performance) on a competency. This type of relationship (whereby SMEs indicate that the traits they have are important for successful job performance) is an example of the self-serving bias (which is widely described in the social cognition literature and rarely described in the industrial/organizational psychology literature). An archival dataset covering 57 clerical and technical occupations with 26,682 participants was used. Support was found for the relationship between self-rated performance and importance ratings. Significant relationships (typically in the .30s) were observed for all 31 competencies that were studied. Controls were taken to account for common method bias and differences in the competencies required for each of the 57 occupations. Past research has demonstrated the effects of the self-serving bias on personality-based job analysis ratings. This study was the first to extend these findings to traditional job analysis, which covers other competencies in addition to personality. In addition, this study is the first to use operational field data instead of laboratory data.

A Self-Adaptive Hidden Markov Model for Emotion Classification in Chinese Microblogs

Directory of Open Access Journals (Sweden)

Li Liu

2015-01-01

we propose a modified version of hidden Markov model (HMM classifier, called self-adaptive HMM, whose parameters are optimized by Particle Swarm Optimization algorithms. Since manually labeling large-scale dataset is difficult, we also employ the entropy to decide whether a new unlabeled tweet shall be contained in the training dataset after being assigned an emotion using our HMM-based approach. In the experiment, we collected about 200,000 Chinese tweets from Sina Weibo. The results show that the F-score of our approach gets 76% on happiness and fear and 65% on anger, surprise, and sadness. In addition, the self-adaptive HMM classifier outperforms Naive Bayes and Support Vector Machine on recognition of happiness, anger, and sadness.

Self-Adaptive Event-Driven Simulation of Multi-Scale Plasma Systems

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Omelchenko, Yuri; Karimabadi, Homayoun

2005-10-01

Multi-scale plasmas pose a formidable computational challenge. The explicit time-stepping models suffer from the global CFL restriction. Efficient application of adaptive mesh refinement (AMR) to systems with irregular dynamics (e.g. turbulence, diffusion-convection-reaction, particle acceleration etc.) may be problematic. To address these issues, we developed an alternative approach to time stepping: self-adaptive discrete-event simulation (DES). DES has origin in operations research, war games and telecommunications. We combine finite-difference and particle-in-cell techniques with this methodology by assuming two caveats: (1) a local time increment, dt for a discrete quantity f can be expressed in terms of a physically meaningful quantum value, df; (2) f is considered to be modified only when its change exceeds df. Event-driven time integration is self-adaptive as it makes use of causality rules rather than parametric time dependencies. This technique enables asynchronous flux-conservative update of solution in accordance with local temporal scales, removes the curse of the global CFL condition, eliminates unnecessary computation in inactive spatial regions and results in robust and fast parallelizable codes. It can be naturally combined with various mesh refinement techniques. We discuss applications of this novel technology to diffusion-convection-reaction systems and hybrid simulations of magnetosonic shocks.

Host-selected mutations converging on a global regulator drive an adaptive leap towards symbiosis in bacteria

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Sabrina Pankey, M; Foxall, Randi L; Ster, Ian M; Perry, Lauren A; Schuster, Brian M; Donner, Rachel A; Coyle, Matthew; Cooper, Vaughn S; Whistler, Cheryl A

2017-01-01

Host immune and physical barriers protect against pathogens but also impede the establishment of essential symbiotic partnerships. To reveal mechanisms by which beneficial organisms adapt to circumvent host defenses, we experimentally evolved ecologically distinct bioluminescent Vibrio fischeri by colonization and growth within the light organs of the squid Euprymna scolopes. Serial squid passaging of bacteria produced eight distinct mutations in the binK sensor kinase gene, which conferred an exceptional selective advantage that could be demonstrated through both empirical and theoretical analysis. Squid-adaptive binK alleles promoted colonization and immune evasion that were mediated by cell-associated matrices including symbiotic polysaccharide (Syp) and cellulose. binK variation also altered quorum sensing, raising the threshold for luminescence induction. Preexisting coordinated regulation of symbiosis traits by BinK presented an efficient solution where altered BinK function was the key to unlock multiple colonization barriers. These results identify a genetic basis for microbial adaptability and underscore the importance of hosts as selective agents that shape emergent symbiont populations. DOI: http://dx.doi.org/10.7554/eLife.24414.001 PMID:28447935

Experimental Evolution of UV-C Radiation Tolerance: Emergence of Adaptive and Non-Adaptive Traits in Escherichia coli Under Differing Flux Regimes

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Moffet, A.; Okansinski, A.; Sloan, C.; Grace, J. M.; Paulino-Lima, I. G.; Gentry, D.; Rothschild, L. J.; Camps, M.

2014-12-01

High-energy ultraviolet (UV-C) radiation is a significant challenge to life in environments such as high altitude areas, the early Earth, the Martian surface, and space. As UV-C exposure is both a selection pressure and a mutagen, adaptation dynamics in such environments include a high rate of change in both tolerance-related and non-tolerance-related genes, as well changes in linkages between the resulting traits. Determining the relationship between the intensity and duration of the UV-C exposure, mutation rate, and emergence of UV-C resistance will inform our understanding of both the emergence of radiation-related extremophily in natural environments and the optimal strategies for generating artificial extremophiles. In this study, we iteratively exposed an Escherichia colistrain to UV-C radiation of two different fluxes, 3.3 J/m^2/s for 6 seconds and 0.5 J/m^2/s for 40 seconds, with the same overall fluence of 20 J/m^2. After each iteration, cells from each exposure regime were assayed for increased UV-C tolerance as an adaptive trait. The exposed cells carried a plasmid bearing a TEM beta-lactamase gene, which in the absence of antibiotic treatment is a neutral reporter for mutagenesis. Sequencing of this gene allowed us to determine the baseline mutation frequency for each flux. As an additional readout for adaptation, the presence of extended-spectrum beta-lactamase mutations was tested by plating UV-exposed cultures in cefotaxime plates. We observed an increase of approximately one-million-fold in UV-C tolerance over seven iterations; no significant difference between the two fluxes was found. Future work will focus on identifying the genomic changes responsible for the change in UV-C tolerance; determining the mechanisms of the emerged UV-C tolerance; and performing competition experiments between the iteration strains to quantify fitness tradeoffs resulting from UV-C adaptation.

[Poor self-rated mastication and associated factors in Brazilian adults].

Science.gov (United States)

Braga, Ana Paula Gasparini; Barreto, Sandhi Maria; Martins, Andréa Maria Eleutério de Barros Lima

2012-05-01

This study estimated the prevalence of bad/very bad self-rated mastication and investigated associated factors among Brazilian adults. The sample included 13,431 adults examined and interviewed in the SBBrazil project. Self-rated mastication was combined in three categories: good/ very good (the reference), fair, and bad/very bad. Multinomial logistic regression was performed to measure the association between fair and bad/very bad self-rated mastication and all independent variables included in the analysis, with significance set at p mastication as good/very good, 24.9% as fair, and 19.5% as bad/very bad. In the final multivariate analysis, factors associated with bad or fair self-rated mastication were: receiving no information on how to avoid oral problems; presenting fewer than 23 remaining teeth; requiring total or partial prosthesis; bad/very bad self-rated oral health; gingival pain and/or toothache in the previous year; and need of dental treatment. In conclusion, various factors were associated with self-rated mastication, especially subjective conditions, thus emphasizing its importance as an oral health indicator.

Self-adaptive global best harmony search algorithm applied to reactor core fuel management optimization

International Nuclear Information System (INIS)

Poursalehi, N.; Zolfaghari, A.; Minuchehr, A.; Valavi, K.

2013-01-01

Highlights: • SGHS enhanced the convergence rate of LPO using some improvements in comparison to basic HS and GHS. • SGHS optimization algorithm obtained averagely better fitness relative to basic HS and GHS algorithms. • Upshot of the SGHS implementation in the LPO reveals its flexibility, efficiency and reliability. - Abstract: The aim of this work is to apply the new developed optimization algorithm, Self-adaptive Global best Harmony Search (SGHS), for PWRs fuel management optimization. SGHS algorithm has some modifications in comparison with basic Harmony Search (HS) and Global-best Harmony Search (GHS) algorithms such as dynamically change of parameters. For the demonstration of SGHS ability to find an optimal configuration of fuel assemblies, basic Harmony Search (HS) and Global-best Harmony Search (GHS) algorithms also have been developed and investigated. For this purpose, Self-adaptive Global best Harmony Search Nodal Expansion package (SGHSNE) has been developed implementing HS, GHS and SGHS optimization algorithms for the fuel management operation of nuclear reactor cores. This package uses developed average current nodal expansion code which solves the multi group diffusion equation by employment of first and second orders of Nodal Expansion Method (NEM) for two dimensional, hexagonal and rectangular geometries, respectively, by one node per a FA. Loading pattern optimization was performed using SGHSNE package for some test cases to present the SGHS algorithm capability in converging to near optimal loading pattern. Results indicate that the convergence rate and reliability of the SGHS method are quite promising and practically, SGHS improves the quality of loading pattern optimization results relative to HS and GHS algorithms. As a result, it has the potential to be used in the other nuclear engineering optimization problems

Self-medication as adaptive plasticity: increased ingestion of plant toxins by parasitized caterpillars.

Directory of Open Access Journals (Sweden)

Michael S Singer

Full Text Available Self-medication is a specific therapeutic behavioral change in response to disease or parasitism. The empirical literature on self-medication has so far focused entirely on identifying cases of self-medication in which particular behaviors are linked to therapeutic outcomes. In this study, we frame self-medication in the broader realm of adaptive plasticity, which provides several testable predictions for verifying self-medication and advancing its conceptual significance. First, self-medication behavior should improve the fitness of animals infected by parasites or pathogens. Second, self-medication behavior in the absence of infection should decrease fitness. Third, infection should induce self-medication behavior. The few rigorous studies of self-medication in non-human animals have not used this theoretical framework and thus have not tested fitness costs of self-medication in the absence of disease or parasitism. Here we use manipulative experiments to test these predictions with the foraging behavior of woolly bear caterpillars (Grammia incorrupta; Lepidoptera: Arctiidae in response to their lethal endoparasites (tachinid flies. Our experiments show that the ingestion of plant toxins called pyrrolizidine alkaloids improves the survival of parasitized caterpillars by conferring resistance against tachinid flies. Consistent with theoretical prediction, excessive ingestion of these toxins reduces the survival of unparasitized caterpillars. Parasitized caterpillars are more likely than unparasitized caterpillars to specifically ingest large amounts of pyrrolizidine alkaloids. This case challenges the conventional view that self-medication behavior is restricted to animals with advanced cognitive abilities, such as primates, and empowers the science of self-medication by placing it in the domain of adaptive plasticity theory.

Self-rated and observer-rated measures of well-being and distress in adolescence: an exploratory study.

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Vescovelli, Francesca; Albieri, Elisa; Ruini, Chiara

2014-01-01

The evaluation of eudaimonic well-being in adolescence is hampered by the lack of specific assessment tools. Moreover, with younger populations, the assessment of positive functioning may be biased by self-report data only, and may be more accurate by adding significant adults' evaluations. The objective of this research was to measure adolescents' well-being and prosocial behaviours using self-rated and observer-rated instruments, and their pattern of associations. The sample included 150 Italian high school adolescents. Observed-evaluation was performed by their school teachers using the Strengths and Difficulties Questionnaire. Adolescents completed Ryff's Psychological Well-being Scales and Symptom Questionnaire. Pearson' r correlations and Linear regression were performed. Self-rated dimensions of psychological well-being significantly correlated with all observer-rated dimensions, but Strengths and Difficulties Emotional symptom scale. Multiple linear regression showed that the self-rated dimensions Environmental Mastery and Personal Growth, and surprisingly not Positive Relations, are related to the observer-rated dimension Prosocial Behaviour. Adolescents with higher levels of well-being in specific dimensions tend to be perceived as less problematic by their teachers. However, some dimensions of positive functioning present discrepancies between self and observer-rated instruments. Thus, the conjunct use of self-reports and observer-rated tools for a more comprehensive assessment of students' eudaimonic well-being is recommended.

Mutator activity in Schizophyllum commune

Energy Technology Data Exchange (ETDEWEB)

Shneyour, Y.; Koltin, Y. (Tel Aviv Univ. (Israel). Dept. of Microbiology)

1983-01-01

A strain with an elevated level of spontaneous mutations and an especially high rate of reversion at a specific locus (pab/sup -/) was identified. The mutator trait is recessive. UV sensitivity and the absence of a UV-specific endonucleolytic activity were associated with the enhancement of the mutation rate in mutator strains. The endonuclease associated with the regulation of the mutation rate also acted on single-stranded DNA. The molecular weight of this enzyme is about 38,000 daltons.

A Fiber Bragg Grating Interrogation System with Self-Adaption Threshold Peak Detection Algorithm.

Science.gov (United States)

Zhang, Weifang; Li, Yingwu; Jin, Bo; Ren, Feifei; Wang, Hongxun; Dai, Wei