WorldWideScience

Sample records for mutation rate adaptation

  1. Variable mutation rates as an adaptive strategy in replicator populations.

    Directory of Open Access Journals (Sweden)

    Michael Stich

    2010-06-01

    Full Text Available For evolving populations of replicators, there is much evidence that the effect of mutations on fitness depends on the degree of adaptation to the selective pressures at play. In optimized populations, most mutations have deleterious effects, such that low mutation rates are favoured. In contrast to this, in populations thriving in changing environments a larger fraction of mutations have beneficial effects, providing the diversity necessary to adapt to new conditions. What is more, non-adapted populations occasionally benefit from an increase in the mutation rate. Therefore, there is no optimal universal value of the mutation rate and species attempt to adjust it to their momentary adaptive needs. In this work we have used stationary populations of RNA molecules evolving in silico to investigate the relationship between the degree of adaptation of an optimized population and the value of the mutation rate promoting maximal adaptation in a short time to a new selective pressure. Our results show that this value can significantly differ from the optimal value at mutation-selection equilibrium, being strongly influenced by the structure of the population when the adaptive process begins. In the short-term, highly optimized populations containing little variability respond better to environmental changes upon an increase of the mutation rate, whereas populations with a lower degree of optimization but higher variability benefit from reducing the mutation rate to adapt rapidly. These findings show a good agreement with the behaviour exhibited by actual organisms that replicate their genomes under broadly different mutation rates.

  2. High mutation rates limit evolutionary adaptation in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Kathleen Sprouffske

    2018-04-01

    Full Text Available Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli's genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this diversity conveyed benefits only for modestly increased mutation rates, where populations adapted faster and also thrived better than their ancestors in some novel environments. In contrast, some populations at the highest mutation rates showed reduced adaptation during evolution, and failed to thrive in all of the 90 alternative environments. In addition, they experienced a dramatic decrease in mutation rate. Our work demonstrates that the mutation rate changes the global balance between deleterious and beneficial mutational effects on fitness. In contrast to most theoretical models, our experiments suggest that this tipping point already occurs at the modest mutation rates that are found in the wild.

  3. High mutation rates limit evolutionary adaptation in Escherichia coli

    Science.gov (United States)

    Wagner, Andreas

    2018-01-01

    Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli’s genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this diversity conveyed benefits only for modestly increased mutation rates, where populations adapted faster and also thrived better than their ancestors in some novel environments. In contrast, some populations at the highest mutation rates showed reduced adaptation during evolution, and failed to thrive in all of the 90 alternative environments. In addition, they experienced a dramatic decrease in mutation rate. Our work demonstrates that the mutation rate changes the global balance between deleterious and beneficial mutational effects on fitness. In contrast to most theoretical models, our experiments suggest that this tipping point already occurs at the modest mutation rates that are found in the wild. PMID:29702649

  4. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-01-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

  5. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-04-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.

  6. 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

  7. Experiments on the role of deleterious mutations as stepping stones in adaptive evolution

    Science.gov (United States)

    Covert, Arthur W.; Lenski, Richard E.; Wilke, Claus O.; Ofria, Charles

    2013-01-01

    Many evolutionary studies assume that deleterious mutations necessarily impede adaptive evolution. However, a later mutation that is conditionally beneficial may interact with a deleterious predecessor before it is eliminated, thereby providing access to adaptations that might otherwise be inaccessible. It is unknown whether such sign-epistatic recoveries are inconsequential events or an important factor in evolution, owing to the difficulty of monitoring the effects and fates of all mutations during experiments with biological organisms. Here, we used digital organisms to compare the extent of adaptive evolution in populations when deleterious mutations were disallowed with control populations in which such mutations were allowed. Significantly higher fitness levels were achieved over the long term in the control populations because some of the deleterious mutations served as stepping stones across otherwise impassable fitness valleys. As a consequence, initially deleterious mutations facilitated the evolution of complex, beneficial functions. We also examined the effects of disallowing neutral mutations, of varying the mutation rate, and of sexual recombination. Populations evolving without neutral mutations were able to leverage deleterious and compensatory mutation pairs to overcome, at least partially, the absence of neutral mutations. Substantially raising or lowering the mutation rate reduced or eliminated the long-term benefit of deleterious mutations, but introducing recombination did not. Our work demonstrates that deleterious mutations can play an important role in adaptive evolution under at least some conditions. PMID:23918358

  8. Spontaneous mutation rates and the rate-doubling dose

    International Nuclear Information System (INIS)

    Von Borstel, R.C.; Moustaccki, E.; Latarjet, R.

    1978-01-01

    The amount of radiation required to double the frequency of mutations or tumours over the rate of those that occur spontaneously is called the rate-doubling dose. An equivalent concept has been proposed for exposure to other environmental mutagens. The doubling dose concept is predicated on the assumption that all human populations have the same spontaneous mutation rate, and that this spontaneous mutation rate is known. It is now established for prokaryotes and lower eukaryotes that numerous genes control the spontaneous mutation rate, and it is likely that the same is true for human cells as well. Given that the accepted mode of evolution of human populatons is from small, isolated groups of individuals, it seems likely that each population would have a different spontaneous mutation rate. Given that a minimum of twenty genes control or affect the spontaneous mutation rate, and that each of these in turn is susceptible to spontaneously arising or environmentally induced mutations, it seems likely that every individual within a population (except for siblings from identical multiple births) will have a unique spontaneous mutation rate. If each individual in a population does have a different spontaneous mutation rate, the doubling dose concept, in rigorous terms, is fallacious. Therefore, as with other concepts of risk evaluation, the doubling dose concept is subject to criticism. Nevertheless, until we know individual spontaneous mutation rates with precision, and can evaluate risks based on this information, the doubling dose concept has a heuristic value and is needed for practical assessment of risks for defined populations. (author)

  9. 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)....

  10. 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

  11. Sex enhances adaptation by unlinking beneficial from detrimental mutations in experimental yeast populations

    Directory of Open Access Journals (Sweden)

    Gray Jeremy C

    2012-03-01

    Full Text Available Abstract Background The maintenance of sexuality is a classic problem in evolutionary biology because it is a less efficient mode of reproduction compared with asexuality; however, many organisms are sexual. Theoretical work suggests sex facilitates natural selection, and experimental data support this. However, there are fewer experimental studies that have attempted to determine the mechanisms underlying the advantage of sex. Two main classes of hypotheses have been proposed to explain its advantage: detrimental mutation clearance and beneficial mutation accumulation. Here we attempt to experimentally differentiate between these two classes by evolving Saccharomyces cerevisiae populations that differ only in their ability to undergo sex, and also manipulate mutation rate. We cannot manipulate the types of mutation that occur, but instead propagate populations in both stressful and permissive environments and assume that the extent of detrimental mutation clearance and beneficial mutation incorporation differs between them. Results After 300 mitotic generations interspersed with 11 rounds of sex we found there was no change or difference in fitness between sexuals and asexuals propagated in the permissive environment, regardless of mutation rate. Sex conferred a greater extent of adaptation in the stressful environment, and wild-type and elevated mutation rate sexual populations adapted equivalently. However, the asexual populations with an elevated mutation rate appeared more retarded in their extent of adaptation compared to asexual wild-type populations. Conclusions Sex provided no advantage in the permissive environment where beneficial mutations were rare. We could not evaluate if sex functioned to clear detrimental mutations more effectively or not here as no additional fitness load was observed in the mutator populations. However, in the stressful environment, where detrimental mutations were likely of more consequence, and where

  12. 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.

  13. Whole genome sequencing of mutation accumulation lines reveals a low mutation rate in the social amoeba Dictyostelium discoideum.

    Directory of Open Access Journals (Sweden)

    Gerda Saxer

    Full Text Available Spontaneous mutations play a central role in evolution. Despite their importance, mutation rates are some of the most elusive parameters to measure in evolutionary biology. The combination of mutation accumulation (MA experiments and whole-genome sequencing now makes it possible to estimate mutation rates by directly observing new mutations at the molecular level across the whole genome. We performed an MA experiment with the social amoeba Dictyostelium discoideum and sequenced the genomes of three randomly chosen lines using high-throughput sequencing to estimate the spontaneous mutation rate in this model organism. The mitochondrial mutation rate of 6.76×10(-9, with a Poisson confidence interval of 4.1×10(-9 - 9.5×10(-9, per nucleotide per generation is slightly lower than estimates for other taxa. The mutation rate estimate for the nuclear DNA of 2.9×10(-11, with a Poisson confidence interval ranging from 7.4×10(-13 to 1.6×10(-10, is the lowest reported for any eukaryote. These results are consistent with low microsatellite mutation rates previously observed in D. discoideum and low levels of genetic variation observed in wild D. discoideum populations. In addition, D. discoideum has been shown to be quite resistant to DNA damage, which suggests an efficient DNA-repair mechanism that could be an adaptation to life in soil and frequent exposure to intracellular and extracellular mutagenic compounds. The social aspect of the life cycle of D. discoideum and a large portion of the genome under relaxed selection during vegetative growth could also select for a low mutation rate. This hypothesis is supported by a significantly lower mutation rate per cell division in multicellular eukaryotes compared with unicellular eukaryotes.

  14. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

  15. 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

  16. 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...

  17. Avoiding dangerous missense: thermophiles display especially low mutation rates.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. Minisatellite germline mutation rate in the Techa River population

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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

  1. Sexual selection, germline mutation rate and sperm competition

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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)

  4. 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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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...

  9. 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.

  10. Codon adaptation and synonymous substitution rate in diatom plastid genes.

    Science.gov (United States)

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Monotonicity of fitness landscapes and mutation rate control.

    Science.gov (United States)

    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.

  16. 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.

  17. 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.

  18. 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…

  19. 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...

  20. 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.)

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

    Science.gov (United States)

    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

  2. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak, E-mail: Siamak.haghdoost@su.se

    2015-10-15

    Highlights: • 50 mGy at 1.4 mGy/h induces adaptive response in MCF-10A at mutation level. • Low dose rate γ-radiation does not induce adaptive response at survival level. • Overall, a dose rate effect is absent at the level of mutation in MCF-10A cells. - Abstract: A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (0.40 Gy/min) or chronically (1.4 mGy/h or 4.1 mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100 mGy and 1 Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50 mGy at 1.4 mGy/h followed by 1 Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100 mGy), no differences at the level of mutation were found comparing different dose rates.

  3. 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

  4. 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

  5. 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.

  6. Contribution of silent mutations to thermal adaptation of RNA bacteriophage Qβ.

    Science.gov (United States)

    Kashiwagi, Akiko; Sugawara, Ryu; Sano Tsushima, Fumie; Kumagai, Tomofumi; Yomo, Tetsuya

    2014-10-01

    Changes in protein function and other biological properties, such as RNA structure, are crucial for adaptation of organisms to novel or inhibitory environments. To investigate how mutations that do not alter amino acid sequence may be positively selected, we performed a thermal adaptation experiment using the single-stranded RNA bacteriophage Qβ in which the culture temperature was increased from 37.2°C to 41.2°C and finally to an inhibitory temperature of 43.6°C in a stepwise manner in three independent lines. Whole-genome analysis revealed 31 mutations, including 14 mutations that did not result in amino acid sequence alterations, in this thermal adaptation. Eight of the 31 mutations were observed in all three lines. Reconstruction and fitness analyses of Qβ strains containing only mutations observed in all three lines indicated that five mutations that did not result in amino acid sequence changes but increased the amplification ratio appeared in the course of adaptation to growth at 41.2°C. Moreover, these mutations provided a suitable genetic background for subsequent mutations, altering the fitness contribution from deleterious to beneficial. These results clearly showed that mutations that do not alter the amino acid sequence play important roles in adaptation of this single-stranded RNA virus to elevated temperature. Recent studies using whole-genome analysis technology suggested the importance of mutations that do not alter the amino acid sequence for adaptation of organisms to novel environmental conditions. It is necessary to investigate how these mutations may be positively selected and to determine to what degree such mutations that do not alter amino acid sequences contribute to adaptive evolution. Here, we report the roles of these silent mutations in thermal adaptation of RNA bacteriophage Qβ based on experimental evolution during which Qβ showed adaptation to growth at an inhibitory temperature. Intriguingly, four synonymous mutations and

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  13. The rate and potential relevance of new mutations in a colonizing plant lineage.

    Directory of Open Access Journals (Sweden)

    Moises Exposito-Alonso

    2018-02-01

    Full Text Available By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by "natural evolution experiments" that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions-the subset of mutations that survived natural selection and drift-, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.

  14. 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

  15. 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...

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. 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.

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

    Science.gov (United States)

    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

  1. 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)

  2. 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.

  3. The (1+λ) evolutionary algorithm with self-adjusting mutation rate

    DEFF Research Database (Denmark)

    Doerr, Benjamin; Witt, Carsten; Gießen, Christian

    2017-01-01

    We propose a new way to self-adjust the mutation rate in population-based evolutionary algorithms. Roughly speaking, it consists of creating half the offspring with a mutation rate that is twice the current mutation rate and the other half with half the current rate. The mutation rate is then upd......We propose a new way to self-adjust the mutation rate in population-based evolutionary algorithms. Roughly speaking, it consists of creating half the offspring with a mutation rate that is twice the current mutation rate and the other half with half the current rate. The mutation rate...... is then updated to the rate used in that subpopulation which contains the best offspring. We analyze how the (1 + A) evolutionary algorithm with this self-adjusting mutation rate optimizes the OneMax test function. We prove that this dynamic version of the (1 + A) EA finds the optimum in an expected optimization...... time (number of fitness evaluations) of O(nA/log A + n log n). This time is asymptotically smaller than the optimization time of the classic (1 + A) EA. Previous work shows that this performance is best-possible among all A-parallel mutation-based unbiased black-box algorithms. This result shows...

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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].

  14. 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.

  15. 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.

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  5. How adaptation shapes spike rate oscillations in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Moritz eAugustin

    2013-02-01

    Full Text Available Neural mass signals from in-vivo recordings often show oscillations with frequencies ranging from <1 Hz to 100 Hz. Fast rhythmic activity in the beta and gamma range can be generated by network based mechanisms such as recurrent synaptic excitation-inhibition loops. Slower oscillations might instead depend on neuronal adaptation currents whose timescales range from tens of milliseconds to seconds. Here we investigate how the dynamics of such adaptation currents contribute to spike rate oscillations and resonance properties in recurrent networks of excitatory and inhibitory neurons. Based on a network of sparsely coupled spiking model neurons with two types of adaptation current and conductance based synapses with heterogeneous strengths and delays we use a mean-field approach to analyze oscillatory network activity. For constant external input, we find that spike-triggered adaptation currents provide a mechanism to generate slow oscillations over a wide range of adaptation timescales as long as recurrent synaptic excitation is sufficiently strong. Faster rhythms occur when recurrent inhibition is slower than excitation and oscillation frequency increases with the strength of inhibition. Adaptation facilitates such network based oscillations for fast synaptic inhibition and leads to decreased frequencies. For oscillatory external input, adaptation currents amplify a narrow band of frequencies and cause phase advances for low frequencies in addition to phase delays at higher frequencies. Our results therefore identify the different key roles of neuronal adaptation dynamics for rhythmogenesis and selective signal propagation in recurrent networks.

  6. Design of 2-D Recursive Filters Using Self-adaptive Mutation Differential Evolution Algorithm

    Directory of Open Access Journals (Sweden)

    Lianghong Wu

    2011-08-01

    Full Text Available This paper investigates a novel approach to the design of two-dimensional recursive digital filters using differential evolution (DE algorithm. The design task is reformulated as a constrained minimization problem and is solved by an Self-adaptive Mutation DE algorithm (SAMDE, which adopts an adaptive mutation operator that combines with the advantages of the DE/rand/1/bin strategy and the DE/best/2/bin strategy. As a result, its convergence performance is improved greatly. Numerical experiment results confirm the conclusion. The proposedSAMDE approach is effectively applied to test a numerical example and is compared with previous design methods. The computational experiments show that the SAMDE approach can obtain better results than previous design methods.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. The influence of DNA repair inhibitors on the mutation rate

    International Nuclear Information System (INIS)

    Auzinger, Th.; Hruby, R.

    1980-12-01

    The simultaneous influence of gamma-radiation and DNA-repair inhibiting substances on the mutation frequency of mice was investigated in vivo with the micronucleus test. The detergens Tween 80, vitamin A, and the antiphlogisticum phenylbutazone were used as DNA-repair inhibiting substances. Using the same irradiation doses, a statistic significant increase of mutagenicity respectively micronucleus frequency was found in high concentrations of Tween 80 and in all used dosages of vitamin A, but not in phenylbutazone and in low concentrations of tween. (auth.)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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...

  16. Adaptation and Assessment of a Public Speaking Rating Scale

    Science.gov (United States)

    Iberri-Shea, Gina

    2017-01-01

    Prominent spoken language assessments such as the Oral Proficiency Interview and the Test of Spoken English have been primarily concerned with speaking ability as it relates to conversation. This paper looks at an additional aspect of spoken language ability, namely public speaking. This study used an adapted form of a public speaking rating scale…

  17. 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....

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Proposing an adaptive mutation to improve XCSF performance to classify ADHD and BMD patients

    Science.gov (United States)

    Sadatnezhad, Khadijeh; Boostani, Reza; Ghanizadeh, Ahmad

    2010-12-01

    There is extensive overlap of clinical symptoms observed among children with bipolar mood disorder (BMD) and those with attention deficit hyperactivity disorder (ADHD). Thus, diagnosis according to clinical symptoms cannot be very accurate. It is therefore desirable to develop quantitative criteria for automatic discrimination between these disorders. This study is aimed at designing an efficient decision maker to accurately classify ADHD and BMD patients by analyzing their electroencephalogram (EEG) signals. In this study, 22 channels of EEGs have been recorded from 21 subjects with ADHD and 22 individuals with BMD. Several informative features, such as fractal dimension, band power and autoregressive coefficients, were extracted from the recorded signals. Considering the multimodal overlapping distribution of the obtained features, linear discriminant analysis (LDA) was used to reduce the input dimension in a more separable space to make it more appropriate for the proposed classifier. A piecewise linear classifier based on the extended classifier system for function approximation (XCSF) was modified by developing an adaptive mutation rate, which was proportional to the genotypic content of best individuals and their fitness in each generation. The proposed operator controlled the trade-off between exploration and exploitation while maintaining the diversity in the classifier's population to avoid premature convergence. To assess the effectiveness of the proposed scheme, the extracted features were applied to support vector machine, LDA, nearest neighbor and XCSF classifiers. To evaluate the method, a noisy environment was simulated with different noise amplitudes. It is shown that the results of the proposed technique are more robust as compared to conventional classifiers. Statistical tests demonstrate that the proposed classifier is a promising method for discriminating between ADHD and BMD patients.

  3. 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.

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

    Science.gov (United States)

    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

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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

  11. 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 ...

  12. 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.

  13. A globally convergent MC algorithm with an adaptive learning rate.

    Science.gov (United States)

    Peng, Dezhong; Yi, Zhang; Xiang, Yong; Zhang, Haixian

    2012-02-01

    This brief deals with the problem of minor component analysis (MCA). Artificial neural networks can be exploited to achieve the task of MCA. Recent research works show that convergence of neural networks based MCA algorithms can be guaranteed if the learning rates are less than certain thresholds. However, the computation of these thresholds needs information about the eigenvalues of the autocorrelation matrix of data set, which is unavailable in online extraction of minor component from input data stream. In this correspondence, we introduce an adaptive learning rate into the OJAn MCA algorithm, such that its convergence condition does not depend on any unobtainable information, and can be easily satisfied in practical applications.

  14. 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.

  15. Controlling the local false discovery rate in the adaptive Lasso

    KAUST Repository

    Sampson, J. N.

    2013-04-09

    The Lasso shrinkage procedure achieved its popularity, in part, by its tendency to shrink estimated coefficients to zero, and its ability to serve as a variable selection procedure. Using data-adaptive weights, the adaptive Lasso modified the original procedure to increase the penalty terms for those variables estimated to be less important by ordinary least squares. Although this modified procedure attained the oracle properties, the resulting models tend to include a large number of "false positives" in practice. Here, we adapt the concept of local false discovery rates (lFDRs) so that it applies to the sequence, λn, of smoothing parameters for the adaptive Lasso. We define the lFDR for a given λn to be the probability that the variable added to the model by decreasing λn to λn-δ is not associated with the outcome, where δ is a small value. We derive the relationship between the lFDR and λn, show lFDR =1 for traditional smoothing parameters, and show how to select λn so as to achieve a desired lFDR. We compare the smoothing parameters chosen to achieve a specified lFDR and those chosen to achieve the oracle properties, as well as their resulting estimates for model coefficients, with both simulation and an example from a genetic study of prostate specific antigen.

  16. 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

  17. 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.

  18. Adaptive Rate Sampling and Filtering Based on Level Crossing Sampling

    Directory of Open Access Journals (Sweden)

    Saeed Mian Qaisar

    2009-01-01

    Full Text Available The recent sophistications in areas of mobile systems and sensor networks demand more and more processing resources. In order to maintain the system autonomy, energy saving is becoming one of the most difficult industrial challenges, in mobile computing. Most of efforts to achieve this goal are focused on improving the embedded systems design and the battery technology, but very few studies target to exploit the input signal time-varying nature. This paper aims to achieve power efficiency by intelligently adapting the processing activity to the input signal local characteristics. It is done by completely rethinking the processing chain, by adopting a non conventional sampling scheme and adaptive rate filtering. The proposed approach, based on the LCSS (Level Crossing Sampling Scheme presents two filtering techniques, able to adapt their sampling rate and filter order by online analyzing the input signal variations. Indeed, the principle is to intelligently exploit the signal local characteristics—which is usually never considered—to filter only the relevant signal parts, by employing the relevant order filters. This idea leads towards a drastic gain in the computational efficiency and hence in the processing power when compared to the classical techniques.

  19. DNA mutations mediate microevolution between host-adapted forms of the pathogenic fungus Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Denise A Magditch

    Full Text Available The disease cryptococcosis, caused by the fungus Cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. One explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. However, co-incubation of C. neoformans with amoeba can cause a "switch" from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence in mammalian models of cryptococcosis. Like other human pathogenic fungi, C. neoformans is capable of microevolutionary changes that influence the biology of the organism and outcome of the host-pathogen interaction. A yeast-pseudohyphal phenotypic switch also happens under in vitro conditions. Here, we demonstrate that this morphological switch, rather than being under epigenetic control, is controlled by DNA mutation since all pseudohyphal strains bear mutations within genes encoding components of the RAM pathway. High rates of isolation of pseudohyphal strains can be explained by the physical size of RAM pathway genes and a hypermutator phenotype of the strain used in phenotypic switching studies. Reversion to wild type yeast morphology in vitro or within a mammalian host can occur through different mechanisms, with one being counter-acting mutations. Infection of mice with RAM mutants reveals several outcomes: clearance of the infection, asymptomatic maintenance of the strains, or reversion to wild type forms and progression of disease. These findings demonstrate a key role of mutation events in microevolution to modulate the ability of a fungal pathogen to cause disease.

  20. Rate Adaptive Selective Segment Assignment for Reliable Wireless Video Transmission

    Directory of Open Access Journals (Sweden)

    Sajid Nazir

    2012-01-01

    Full Text Available A reliable video communication system is proposed based on data partitioning feature of H.264/AVC, used to create a layered stream, and LT codes for erasure protection. The proposed scheme termed rate adaptive selective segment assignment (RASSA is an adaptive low-complexity solution to varying channel conditions. The comparison of the results of the proposed scheme is also provided for slice-partitioned H.264/AVC data. Simulation results show competitiveness of the proposed scheme compared to optimized unequal and equal error protection solutions. The simulation results also demonstrate that a high visual quality video transmission can be maintained despite the adverse effect of varying channel conditions and the number of decoding failures can be reduced.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Germline mutation rates in mice following in utero exposure to diesel exhaust particles by maternal inhalation

    DEFF Research Database (Denmark)

    Ritz, Caitlin; Ruminski, Wojciech; Hougaard, Karin S.

    2011-01-01

    (PAPs) from industrial environments cause DNA damage and mutations in the sperm of adult male mice. Effects on the female and male germline during critical stages of development (in utero) are unknown. In mice, previous studies have shown that expanded simple tandem repeat (ESTR) loci exhibit high rates......The induction of inherited DNA sequence mutations arising in the germline (i.e., sperm or egg) of mice exposed in utero to diesel exhaust particles (DEPs) via maternal inhalation compared to unexposed controls was investigated in this study. Previous work has shown that particulate air pollutants...... of spontaneous mutation, making this endpoint a valuable tool for studying inherited mutation and genomic instability. In the present study, pregnant C57Bl/6 mice were exposed to 19mg/m3 DEP from gestational day 7 through 19, alongside air exposed controls. Male and female F1 offspring were raised to maturity...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

    DEFF Research Database (Denmark)

    Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.

    2015-01-01

    Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole...... DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...

  10. 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)

  11. 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

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

    Science.gov (United States)

    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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. 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.)

  18. PENERAPAN FITUR ADAPTIVE MULTI RATE (AMR PADA JARINGAN GSM

    Directory of Open Access Journals (Sweden)

    Abdusy Syarif

    2010-05-01

    Full Text Available Adaptive Mutlirate (AMR is a feature that plays an important role in the efficiency of use of cell/voice channels and GSM networks in overall and it can improve sound quality dynamically based on actual measurements (real time between Mobile Station (MS and Base Transmitter Station (BTS. Resources used as analytical parameters are SQI (Speech Quality Index, MOS (Mean Opinion Score and the sound quality on the network without and with AMR. Measurements using Test Equipment Mobile System (TEMS while locking devices to the single channel and comparing them between the two types of network. Based on test results it is obtained that with voice channels with AMR can increase the value of SQI approximately 40% for fullrate channels and about 60% for half-rate channels producing a remarkable (excellent level, with research and further measuring it is expected to produce better and more perfect sound quality.Kata kunci: AMR, SQI, GSM networkABSTRAK

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

    Science.gov (United States)

    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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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....

  3. 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.

  4. 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.

  5. Discrete rate and variable power adaptation for underlay cognitive networks

    KAUST Repository

    Abdallah, Mohamed M.

    2010-01-01

    We consider the problem of maximizing the average spectral efficiency of a secondary link in underlay cognitive networks. In particular, we consider the network setting whereby the secondary transmitter employs discrete rate and variable power adaptation under the constraints of maximum average transmit power and maximum average interference power allowed at the primary receiver due to the existence of an interference link between the secondary transmitter and the primary receiver. We first find the optimal discrete rates assuming a predetermined partitioning of the signal-to-noise ratio (SNR) of both the secondary and interference links. We then present an iterative algorithm for finding a suboptimal partitioning of the SNR of the interference link assuming a fixed partitioning of the SNR of secondary link selected for the case where no interference link exists. Our numerical results show that the average spectral efficiency attained by using the iterative algorithm is close to that achieved by the computationally extensive exhaustive search method for the case of Rayleigh fading channels. In addition, our simulations show that selecting the optimal partitioning of the SNR of the secondary link assuming no interference link exists still achieves the maximum average spectral efficiency for the case where the average interference constraint is considered. © 2010 IEEE.

  6. 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.

  7. 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

  8. Mutation breeding in Ajonjoli (Sesamum indicum, L.) for adaptation to the cropping system in Venezuela

    International Nuclear Information System (INIS)

    Oropeza, F.; Murty, B.R.; Bravo, R.M.

    1984-01-01

    Sesame, the main edible oil crop in Venezuela, is grown in a cropping system under peculiar ecological conditions after rice, sorghum or maize on residual moisture. The yields are variable with 350 to 500 Kg/Ha. The available varieties are not synchronous in flowering, have poor root development, and are susceptible to Fusarium sp, Phytophtora and Macrophomina. Some are very late (more than 115 days) with 1-3 capsules of variable size and unpredictable yield. A mutational rectification program using locally adapted varieties was started in 1981, to develop material suitable for the above ecological conditions. The main characteristics for improvement are: earliness, with maturity of 75 to 90 days, synchronous flowering, uniform ripening, indehiscence at harvesting but easy threshing, suitable plant type for mechanical harvesting, resistance specially to Macrophomina spp, without adverse effect on oil content, quality and yield and improved productivity and stability under moisture stress and improved fertilizer utilization. Eight varieties were treated with gamma radiation from Csub(o) 60 at 0, 20, 40, 60, 80 KR to determine varietal responses. The results show marked varietal differences in germination, growth and survival. The other three varieties: Aceitera, Arawaca, Turen were the most susceptible to radiation, while Glauca was the most resistant. Probit analysis of data for germination, vigor seedling height and survival revealed that no single character is adequate to determine LD 50 dose in mutation breeding. The need for taking all the parameters of regression analysis like b-tilde, and σ-circumflex to characterize varietal responses is discussed along with plans for the next stage of work. (author)

  9. The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis (Adaptive Mutation)

    Science.gov (United States)

    Maisnier-Patin, Sophie; Roth, John R.

    2015-01-01

    Selection detects mutants but does not cause mutations. Contrary to this dictum, Cairns and Foster plated a leaky lac mutant of Escherichia coli on lactose medium and saw revertant (Lac+) colonies accumulate with time above a nongrowing lawn. This result suggested that bacteria might mutagenize their own genome when growth is blocked. However, this conclusion is suspect in the light of recent evidence that revertant colonies are initiated by preexisting cells with multiple copies the conjugative F′lac plasmid, which carries the lac mutation. Some plated cells have multiple copies of the simple F′lac plasmid. This provides sufficient LacZ activity to support plasmid replication but not cell division. In nongrowing cells, repeated plasmid replication increases the likelihood of a reversion event. Reversion to lac+ triggers exponential cell growth leading to a stable Lac+ revertant colony. In 10% of these plated cells, the high-copy plasmid includes an internal tandem lac duplication, which provides even more LacZ activity—sufficient to support slow growth and formation of an unstable Lac+ colony. Cells with multiple copies of the F′lac plasmid have an increased mutation rate, because the plasmid encodes the error-prone (mutagenic) DNA polymerase, DinB. Without DinB, unstable and stable Lac+ revertant types form in equal numbers and both types arise with no mutagenesis. Amplification and selection are central to behavior of the Cairns–Foster system, whereas mutagenesis is a system-specific side effect or artifact caused by coamplification of dinB with lac. Study of this system has revealed several broadly applicable principles. In all populations, gene duplications are frequent stable genetic polymorphisms, common near-neutral mutant alleles can gain a positive phenotype when amplified under selection, and natural selection can operate without cell division when variability is generated by overreplication of local genome subregions. PMID:26134316

  10. 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

  11. 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

  12. 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 ...

  13. 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.

  14. Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline

    DEFF Research Database (Denmark)

    Giannoulatou, Eleni; McVean, Gilean; Taylor, Indira B

    2013-01-01

    Costello syndrome (CS), a congenital disorder associated with predisposition to malignancy. Based on the epidemiology of CS and the occurrence of HRAS mutations in spermatocytic seminoma, we proposed that activating HRAS mutations become enriched in sperm through a process akin to tumorigenesis, termed...

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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.

  5. Multiple Maximum Exposure Rates in Computerized Adaptive Testing

    Science.gov (United States)

    Ramon Barrada, Juan; Veldkamp, Bernard P.; Olea, Julio

    2009-01-01

    Computerized adaptive testing is subject to security problems, as the item bank content remains operative over long periods and administration time is flexible for examinees. Spreading the content of a part of the item bank could lead to an overestimation of the examinees' trait level. The most common way of reducing this risk is to impose a…

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Using An Adapter To Perform The Chalfant-Style Containment Vessel Periodic Maintenance Leak Rate Test

    International Nuclear Information System (INIS)

    Loftin, B.; Abramczyk, G.; Trapp, D.

    2011-01-01

    Recently the Packaging Technology and Pressurized Systems (PT and PS) organization at the Savannah River National Laboratory was asked to develop an adapter for performing the leak-rate test of a Chalfant-style containment vessel. The PT and PS organization collaborated with designers at the Department of Energy's Pantex Plant to develop the adapter currently in use for performing the leak-rate testing on the containment vessels. This paper will give the history of leak-rate testing of the Chalfant-style containment vessels, discuss the design concept for the adapter, give an overview of the design, and will present results of the testing done using the adapter.

  10. Adaptive Mean and Trend Removal of Heart Rate Variability Using Kalman Filtering

    National Research Council Canada - National Science Library

    Schloegl, A

    2001-01-01

    Analysis of heart rate van ability requires the calculation of the mean heart rate, Adaptive methods are important for online and real-time parameter estimation, In this paper we demonstrate the use...

  11. Keeping up with a warming world; assessing the rate of adaptation to climate change

    NARCIS (Netherlands)

    Visser, M.E.

    2008-01-01

    The pivotal question in the debate on the ecological effects of climate change is whether species will be able to adapt fast enough to keep up with their changing environment. If we establish the maximal rate of adaptation, this will set an upper limit to the rate at which temperatures can increase

  12. Accurate and fast methods to estimate the population mutation rate from error prone sequences

    Directory of Open Access Journals (Sweden)

    Miyamoto Michael M

    2009-08-01

    Full Text Available Abstract Background The population mutation rate (θ remains one of the most fundamental parameters in genetics, ecology, and evolutionary biology. However, its accurate estimation can be seriously compromised when working with error prone data such as expressed sequence tags, low coverage draft sequences, and other such unfinished products. This study is premised on the simple idea that a random sequence error due to a chance accident during data collection or recording will be distributed within a population dataset as a singleton (i.e., as a polymorphic site where one sampled sequence exhibits a unique base relative to the common nucleotide of the others. Thus, one can avoid these random errors by ignoring the singletons within a dataset. Results This strategy is implemented under an infinite sites model that focuses on only the internal branches of the sample genealogy where a shared polymorphism can arise (i.e., a variable site where each alternative base is represented by at least two sequences. This approach is first used to derive independently the same new Watterson and Tajima estimators of θ, as recently reported by Achaz 1 for error prone sequences. It is then used to modify the recent, full, maximum-likelihood model of Knudsen and Miyamoto 2, which incorporates various factors for experimental error and design with those for coalescence and mutation. These new methods are all accurate and fast according to evolutionary simulations and analyses of a real complex population dataset for the California seahare. Conclusion In light of these results, we recommend the use of these three new methods for the determination of θ from error prone sequences. In particular, we advocate the new maximum likelihood model as a starting point for the further development of more complex coalescent/mutation models that also account for experimental error and design.

  13. 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.

  14. 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.

  15. [Are positive illusions adaptive?: self- and other-rating].

    Science.gov (United States)

    Toyama, Miki

    2008-08-01

    The present study investigated the relationship between children's overly positive self-perceptions of their own social competence and mental health. Elementary school students (grades fourth to sixth, n=331) and their homeroom teachers (n=9) participated in the study. The positive illusion was measured by the difference between the self-rating and the other (homeroom teachers) -rating. And, the index of mental health was administered in both self-rating and other (homeroom teachers and same-sex classmates) -rating forms. Positive illusions about children's social competence were positively related to self-ratings of mental health. However, the present study also found detrimental effects of such positive illusions. Children with excessively positive views of their social competence were viewed by teachers and same-sex classmates as significantly more aggressive than those children who showed more evidence of self-devaluation. In addition, children with overly positive self-perceptions were not as accepted by same-sex classmates.

  16. Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate

    Directory of Open Access Journals (Sweden)

    Ihssane El Bouchikhi

    2016-12-01

    Full Text Available Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.

  17. Rate adaptation in ad hoc networks based on pricing

    CSIR Research Space (South Africa)

    Awuor, F

    2011-09-01

    Full Text Available that incorporates penalty (pricing) obtruded to users’ choices of transmission parameters to curb the self-interest behaviour. Therefore users determine their data rates and transmit power based on the perceived coupled interference at the intended receiver...

  18. Discrete rate and variable power adaptation for underlay cognitive networks

    KAUST Repository

    Abdallah, Mohamed M.; Salem, Ahmed H.; Alouini, Mohamed-Slim; Qaraqe, Khalid A.

    2010-01-01

    We consider the problem of maximizing the average spectral efficiency of a secondary link in underlay cognitive networks. In particular, we consider the network setting whereby the secondary transmitter employs discrete rate and variable power

  19. Variable Rate, Adaptive Transform Tree Coding Of Images

    Science.gov (United States)

    Pearlman, William A.

    1988-10-01

    A tree code, asymptotically optimal for stationary Gaussian sources and squared error distortion [2], is used to encode transforms of image sub-blocks. The variance spectrum of each sub-block is estimated and specified uniquely by a set of one-dimensional auto-regressive parameters. The expected distortion is set to a constant for each block and the rate is allowed to vary to meet the given level of distortion. Since the spectrum and rate are different for every block, the code tree differs for every block. Coding simulations for target block distortion of 15 and average block rate of 0.99 bits per pel (bpp) show that very good results can be obtained at high search intensities at the expense of high computational complexity. The results at the higher search intensities outperform a parallel simulation with quantization replacing tree coding. Comparative coding simulations also show that the reproduced image with variable block rate and average rate of 0.99 bpp has 2.5 dB less distortion than a similarly reproduced image with a constant block rate equal to 1.0 bpp.

  20. Mutations of different molecular origins exhibit contrasting patterns of regional substitution rate variation.

    Directory of Open Access Journals (Sweden)

    Navin Elango

    2008-02-01

    Full Text Available Transitions at CpG dinucleotides, referred to as "CpG substitutions", are a major mutational input into vertebrate genomes and a leading cause of human genetic disease. The prevalence of CpG substitutions is due to their mutational origin, which is dependent on DNA methylation. In comparison, other single nucleotide substitutions (for example those occurring at GpC dinucleotides mainly arise from errors during DNA replication. Here we analyzed high quality BAC-based data from human, chimpanzee, and baboon to investigate regional variation of CpG substitution rates. We show that CpG substitutions occur approximately 15 times more frequently than other single nucleotide substitutions in primate genomes, and that they exhibit substantial regional variation. Patterns of CpG rate variation are consistent with differences in methylation level and susceptibility to subsequent deamination. In particular, we propose a "distance-decaying" hypothesis, positing that due to the molecular mechanism of a CpG substitution, rates are correlated with the stability of double-stranded DNA surrounding each CpG dinucleotide, and the effect of local DNA stability may decrease with distance from the CpG dinucleotide.Consistent with our "distance-decaying" hypothesis, rates of CpG substitution are strongly (negatively correlated with regional G+C content. The influence of G+C content decays as the distance from the target CpG site increases. We estimate that the influence of local G+C content extends up to 1,500 approximately 2,000 bps centered on each CpG site. We also show that the distance-decaying relationship persisted when we controlled for the effect of long-range homogeneity of nucleotide composition. GpC sites, in contrast, do not exhibit such "distance-decaying" relationship. Our results highlight an example of the distinctive properties of methylation-dependent substitutions versus substitutions mostly arising from errors during DNA replication. Furthermore

  1. 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...

  2. High rate of adaptation of mammalian proteins that interact with Plasmodium and related parasites

    Science.gov (United States)

    Telis, Natalie; Petrov, Dmitri A.

    2017-01-01

    Plasmodium parasites, along with their Piroplasm relatives, have caused malaria-like illnesses in terrestrial mammals for millions of years. Several Plasmodium-protective alleles have recently evolved in human populations, but little is known about host adaptation to blood parasites over deeper evolutionary timescales. In this work, we analyze mammalian adaptation in ~500 Plasmodium- or Piroplasm- interacting proteins (PPIPs) manually curated from the scientific literature. We show that (i) PPIPs are enriched for both immune functions and pleiotropy with other pathogens, and (ii) the rate of adaptation across mammals is significantly elevated in PPIPs, compared to carefully matched control proteins. PPIPs with high pathogen pleiotropy show the strongest signatures of adaptation, but this pattern is fully explained by their immune enrichment. Several pieces of evidence suggest that blood parasites specifically have imposed selection on PPIPs. First, even non-immune PPIPs that lack interactions with other pathogens have adapted at twice the rate of matched controls. Second, PPIP adaptation is linked to high expression in the liver, a critical organ in the parasite life cycle. Finally, our detailed investigation of alpha-spectrin, a major red blood cell membrane protein, shows that domains with particularly high rates of adaptation are those known to interact specifically with P. falciparum. Overall, we show that host proteins that interact with Plasmodium and Piroplasm parasites have experienced elevated rates of adaptation across mammals, and provide evidence that some of this adaptation has likely been driven by blood parasites. PMID:28957326

  3. 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.

  4. A Rate Adaptation Scheme According to Channel Conditions in Wireless LANs

    Science.gov (United States)

    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.

  5. Temporal Coordination and Adaptation to Rate Change in Music Performance

    Science.gov (United States)

    Loehr, Janeen D.; Large, Edward W.; Palmer, Caroline

    2011-01-01

    People often coordinate their actions with sequences that exhibit temporal variability and unfold at multiple periodicities. We compared oscillator- and timekeeper-based accounts of temporal coordination by examining musicians' coordination of rhythmic musical sequences with a metronome that gradually changed rate at the end of a musical phrase…

  6. 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).

  7. Molecular analysis using DHPLC of cystic fibrosis: increase of the mutation detection rate among the affected population in Central Italy

    Directory of Open Access Journals (Sweden)

    Nardone Anna

    2004-04-01

    Full Text Available Abstract Background Cystic fibrosis (CF is a multisystem disorder characterised by mutations of the CFTR gene, which encodes for an important component in the coordination of electrolyte movement across of epithelial cell membranes. Symptoms are pulmonary disease, pancreatic exocrine insufficiency, male infertility and elevated sweat concentrations. The CFTR gene has numerous mutations (>1000 and functionally important polymorphisms (>200. Early identification is important to provide appropriate therapeutic interventions, prognostic and genetic counselling and to ensure access to specialised medical services. However, molecular diagnosis by direct mutation screening has proved difficult in certain ethnic groups due to allelic heterogeneity and variable frequency of causative mutations. Methods We applied a gene scanning approach using DHPLC system for analysing specifically all CFTR exons and characterise sequence variations in a subgroup of CF Italian patients from the Lazio region (Central Italy characterised by an extensive allelic heterogeneity. Results We have identified a total of 36 different mutations representing 88% of the CF chromosomes. Among these are two novel CFTR mutations, including one missense (H199R and one microdeletion (4167delCTAAGCC. Conclusion Using this approach, we were able to increase our standard power rate of mutation detection of about 11% (77% vs. 88%.

  8. Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells

    Science.gov (United States)

    Cucinotta, F. A.; Wilson, J. W.; Shavers, M. R.; Katz, R.

    1996-01-01

    It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to gamma-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from delta-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or Z*2/beta(2) can be used to specify radiation quality for heavy ion bombardment.

  9. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Sehgal S

    2008-01-01

    Full Text Available In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25 of the children while mutation T215Y was found in none. Two of the six drug naοve children also showed K103N mutation. Thus, Indian children drug naοve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

  10. Illusory reversal of causality between touch and vision has no effect on prism adaptation rate

    Directory of Open Access Journals (Sweden)

    Hirokazu eTanaka

    2012-12-01

    Full Text Available Learning, according to Oxford Dictionary, is to gain knowledge or skill by studying, from experience, from being taught, etc. In order to learn from experience, the central nervous system has to decide what action leads to what consequence, and temporal perception plays a critical role in determining the causality between actions and consequences. In motor adaptation, causality between action and consequence is implicitly assumed so that a subject adapts to a new environment based on the consequence caused by her action. Adaptation to visual displacement induced by prisms is a prime example; the visual error signal associated with the motor output contributes to the recovery of accurate reaching, and a delayed feedback of visual error can decrease the adaptation rate. Subjective feeling of temporal order of action and consequence, however, can be modified or even reversed when her sense of simultaneity is manipulated with an artificially delayed feedback. Our previous study (Tanaka, Homma & Imamizu (2011 Exp Brain Res demonstrated that the rate of prism adaptation was unaffected when the subjective delay of visual feedback was shortened. This study asked whether subjects could adapt to prism adaptation and whether the rate of prism adaptation was affected when the subjective temporal order was illusory reversed. Adapting to additional 100 ms delay and its sudden removal caused a positive shift of point of simultaneity in a temporal-order judgment experiment, indicating an illusory reversal of action and consequence. We found that, even in this case, the subjects were able to adapt to prism displacement with the learning rate that was statistically indistinguishable to that without temporal adaptation. This result provides further evidence to the dissociation between conscious temporal perception and motor adaptation.

  11. The adaptation rate of terrestrial ecosystems as a critical factor in global climate dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Fuessler, J S; Gassmann, F [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    A conceptual climate model describing regional two-way atmosphere-vegetation interaction has been extended by a simple qualitative scheme of ecosystem adaptation to drought stress. The results of this explorative study indicate that the role of terrestrial vegetation under different forcing scenarios depends crucially on the rate of the ecosystems adaptation to drought stress. The faster the adaptation of important ecosystems such as forests the better global climate is protected from abrupt climate changes. (author) 1 fig., 3 refs.

  12. Illusory Reversal of Causality between Touch and Vision has No Effect on Prism Adaptation Rate.

    Science.gov (United States)

    Tanaka, Hirokazu; Homma, Kazuhiro; Imamizu, Hiroshi

    2012-01-01

    Learning, according to Oxford Dictionary, is "to gain knowledge or skill by studying, from experience, from being taught, etc." In order to learn from experience, the central nervous system has to decide what action leads to what consequence, and temporal perception plays a critical role in determining the causality between actions and consequences. In motor adaptation, causality between action and consequence is implicitly assumed so that a subject adapts to a new environment based on the consequence caused by her action. Adaptation to visual displacement induced by prisms is a prime example; the visual error signal associated with the motor output contributes to the recovery of accurate reaching, and a delayed feedback of visual error can decrease the adaptation rate. Subjective feeling of temporal order of action and consequence, however, can be modified or even reversed when her sense of simultaneity is manipulated with an artificially delayed feedback. Our previous study (Tanaka et al., 2011; Exp. Brain Res.) demonstrated that the rate of prism adaptation was unaffected when the subjective delay of visual feedback was shortened. This study asked whether subjects could adapt to prism adaptation and whether the rate of prism adaptation was affected when the subjective temporal order was illusory reversed. Adapting to additional 100 ms delay and its sudden removal caused a positive shift of point of simultaneity in a temporal order judgment experiment, indicating an illusory reversal of action and consequence. We found that, even in this case, the subjects were able to adapt to prism displacement with the learning rate that was statistically indistinguishable to that without temporal adaptation. This result provides further evidence to the dissociation between conscious temporal perception and motor adaptation.

  13. Mutation of a cuticular protein, BmorCPR2, alters larval body shape and adaptability in silkworm, Bombyx mori.

    Science.gov (United States)

    Qiao, Liang; Xiong, Gao; Wang, Ri-xin; He, Song-zhen; Chen, Jie; Tong, Xiao-ling; Hu, Hai; Li, Chun-lin; Gai, Ting-ting; Xin, Ya-qun; Liu, Xiao-fan; Chen, Bin; Xiang, Zhong-huai; Lu, Cheng; Dai, Fang-yin

    2014-04-01

    Cuticular proteins (CPs) are crucial components of the insect cuticle. Although numerous genes encoding cuticular proteins have been identified in known insect genomes to date, their functions in maintaining insect body shape and adaptability remain largely unknown. In the current study, positional cloning led to the identification of a gene encoding an RR1-type cuticular protein, BmorCPR2, highly expressed in larval chitin-rich tissues and at the mulberry leaf-eating stages, which is responsible for the silkworm stony mutant. In the Dazao-stony strain, the BmorCPR2 allele is a deletion mutation with significantly lower expression, compared to the wild-type Dazao strain. Dysfunctional BmorCPR2 in the stony mutant lost chitin binding ability, leading to reduced chitin content in larval cuticle, limitation of cuticle extension, abatement of cuticle tensile properties, and aberrant ratio between internodes and intersegmental folds. These variations induce a significant decrease in cuticle capacity to hold the growing internal organs in the larval development process, resulting in whole-body stiffness, tightness, and hardness, bulging intersegmental folds, and serious defects in larval adaptability. To our knowledge, this is the first study to report the corresponding phenotype of stony in insects caused by mutation of RR1-type cuticular protein. Our findings collectively shed light on the specific role of cuticular proteins in maintaining normal larval body shape and will aid in the development of pest control strategies for the management of Lepidoptera.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Adaptation of Lactococcus lactis to high growth temperature leads to a dramatic increase in acidification rate

    DEFF Research Database (Denmark)

    Chen, Jun; Shen, Jing; Hellgren, Lars

    2015-01-01

    temperature. At the maximal permissive temperature for the wild-type, 38 °C, TM29 grows 33% faster and has a 12% higher specific lactate production rate than its parent MG1363, which results in fast lactate accumulation. Genome sequencing was used to reveal the mutations accumulated, most of which were shown...

  18. Job performance ratings : The relative importance of mental ability, conscientiousness, and career adaptability

    NARCIS (Netherlands)

    Ohme, Melanie; Zacher, Hannes

    According to career construction theory, continuous adaptation to the work environment is crucial to achieve work and career success. In this study, we examined the relative importance of career adaptability for job performance ratings using an experimental policy-capturing design. Employees (N =

  19. 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...

  20. 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.

  1. 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.

  2. Poststroke Hemiparesis Impairs the Rate but not Magnitude of Adaptation of Spatial and Temporal Locomotor Features

    Science.gov (United States)

    Savin, Douglas N.; Tseng, Shih-Chiao; Whitall, Jill; Morton, Susanne M.

    2015-01-01

    Background Persons with stroke and hemiparesis walk with a characteristic pattern of spatial and temporal asymmetry that is resistant to most traditional interventions. It was recently shown in nondisabled persons that the degree of walking symmetry can be readily altered via locomotor adaptation. However, it is unclear whether stroke-related brain damage affects the ability to adapt spatial or temporal gait symmetry. Objective Determine whether locomotor adaptation to a novel swing phase perturbation is impaired in persons with chronic stroke and hemiparesis. Methods Participants with ischemic stroke (14) and nondisabled controls (12) walked on a treadmill before, during, and after adaptation to a unilateral perturbing weight that resisted forward leg movement. Leg kinematics were measured bilaterally, including step length and single-limb support (SLS) time symmetry, limb angle center of oscillation, and interlimb phasing, and magnitude of “initial” and “late” locomotor adaptation rates were determined. Results All participants had similar magnitudes of adaptation and similar initial adaptation rates both spatially and temporally. All 14 participants with stroke and baseline asymmetry temporarily walked with improved SLS time symmetry after adaptation. However, late adaptation rates poststroke were decreased (took more strides to achieve adaptation) compared with controls. Conclusions Mild to moderate hemiparesis does not interfere with the initial acquisition of novel symmetrical gait patterns in both the spatial and temporal domains, though it does disrupt the rate at which “late” adaptive changes are produced. Impairment of the late, slow phase of learning may be an important rehabilitation consideration in this patient population. PMID:22367915

  3. Adaptive discrete rate and power transmission for spectrum sharing systems

    KAUST Repository

    Abdallah, Mohamed M.

    2012-04-01

    In this paper we develop a framework for optimizing the performance of the secondary link in terms of the average spectral efficiency assuming quantized channel state information (CSI) of the secondary and the secondary-to-primary interference channels available at the secondary transmitter. We consider the problem under the constraints of maximum average interference power levels at the primary receiver. We develop a sub-optimal computationally efficient iterative algorithm for finding the optimal CSI quantizers as well as the discrete power and rate employed at the cognitive transmitter for each quantized CSI level so as to maximize the average spectral efficiency. We show via analysis and simulations that the proposed algorithm converges for Rayleigh fading channels. Our numerical results give the number of bits required to sufficiently represent the CSI to achieve almost the maximum average spectral efficiency attained using full knowledge of the CSI. © 2012 IEEE.

  4. 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

  5. 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

  6. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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

  9. Adaptation of abbreviated mathematics anxiety rating scale for engineering students

    Science.gov (United States)

    Nordin, Sayed Kushairi Sayed; Samat, Khairul Fadzli; Sultan, Al Amin Mohamed; Halim, Bushra Abdul; Ismail, Siti Fatimah; Mafazi, Nurul Wirdah

    2015-05-01

    Mathematics is an essential and fundamental tool used by engineers to analyse and solve problems in their field. Due to this, most engineering education programs involve a concentration of study in mathematics courses whereby engineering students have to take mathematics courses such as numerical methods, differential equations and calculus in the first two years and continue to do so until the completion of the sequence. However, the students struggled and had difficulties in learning courses that require mathematical abilities. Hence, this study presents the factors that caused mathematics anxiety among engineering students using Abbreviated Mathematics Anxiety Rating Scale (AMARS) through 95 students of Universiti Teknikal Malaysia Melaka (UTeM). From 25 items in AMARS, principal component analysis (PCA) suggested that there are four mathematics anxiety factors, namely experiences of learning mathematics, cognitive skills, mathematics evaluation anxiety and students' perception on mathematics. Minitab 16 software was used to analyse the nonparametric statistics. Kruskal-Wallis Test indicated that there is a significant difference in the experience of learning mathematics and mathematics evaluation anxiety among races. The Chi-Square Test of Independence revealed that the experience of learning mathematics, cognitive skills and mathematics evaluation anxiety depend on the results of their SPM additional mathematics. Based on this study, it is recommended to address the anxiety problems among engineering students at the early stage of studying in the university. Thus, lecturers should play their part by ensuring a positive classroom environment which encourages students to study mathematics without fear.

  10. 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

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

    Science.gov (United States)

    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

  12. 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...

  13. Recovery Act: Energy Efficiency of Data Networks through Rate Adaptation (EEDNRA) - Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Matthew Andrews; Spyridon Antonakopoulos; Steve Fortune; Andrea Francini; Lisa Zhang

    2011-07-12

    This Concept Definition Study focused on developing a scientific understanding of methods to reduce energy consumption in data networks using rate adaptation. Rate adaptation is a collection of techniques that reduce energy consumption when traffic is light, and only require full energy when traffic is at full provisioned capacity. Rate adaptation is a very promising technique for saving energy: modern data networks are typically operated at average rates well below capacity, but network equipment has not yet been designed to incorporate rate adaptation. The Study concerns packet-switching equipment, routers and switches; such equipment forms the backbone of the modern Internet. The focus of the study is on algorithms and protocols that can be implemented in software or firmware to exploit hardware power-control mechanisms. Hardware power-control mechanisms are widely used in the computer industry, and are beginning to be available for networking equipment as well. Network equipment has different performance requirements than computer equipment because of the very fast rate of packet arrival; hence novel power-control algorithms are required for networking. This study resulted in five published papers, one internal report, and two patent applications, documented below. The specific technical accomplishments are the following: • A model for the power consumption of switching equipment used in service-provider telecommunication networks as a function of operating state, and measured power-consumption values for typical current equipment. • An algorithm for use in a router that adapts packet processing rate and hence power consumption to traffic load while maintaining performance guarantees on delay and throughput. • An algorithm that performs network-wide traffic routing with the objective of minimizing energy consumption, assuming that routers have less-than-ideal rate adaptivity. • An estimate of the potential energy savings in service-provider networks

  14. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared...... the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung...... transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...

  15. Replication and adaptive mutations of low pathogenic avian influenza viruses in tracheal organ cultures of different avian species.

    Directory of Open Access Journals (Sweden)

    Henning Petersen

    Full Text Available Transmission of avian influenza viruses (AIV between different avian species may require genome mutations that allow efficient virus replication in a new species and could increase virulence. To study the role of domestic poultry in the evolution of AIV we compared replication of low pathogenic (LP AIV of subtypes H9N2, H7N7 and H6N8 in tracheal organ cultures (TOC and primary embryo fibroblast cultures of chicken, turkey, Pekin duck and homing pigeon. Virus strain-dependent and avian species-related differences between LPAIV were observed in growth kinetics and induction of ciliostasis in TOC. In particular, our data demonstrate high susceptibility to LPAIV of turkey TOC contrasted with low susceptibility of homing pigeon TOC. Serial virus passages in the cells of heterologous host species resulted in adaptive mutations in the AIV genome, especially in the receptor-binding site and protease cleavage site of the hemagglutinin. Our data highlight differences in susceptibility of different birds to AIV viruses and emphasizes potential role of poultry in the emergence of new virus variants.

  16. Channel allocation and rate adaptation for relayed transmission over correlated fading channels

    KAUST Repository

    Hwang, Kyusung; Hossain, Md Jahangir; Ko, Youngchai; Alouini, Mohamed-Slim

    2009-01-01

    at both the source and relay nodes, we develop an optimal channel allocation and rate adaptation policy for a dual-hop relayed transmission. As such the overall transmit power for the relayed system is minimized while a target packet dropping rate (PDR

  17. Model Reference Adaptive Control of the Air Flow Rate of Centrifugal Compressor Using State Space Method

    International Nuclear Information System (INIS)

    Han, Jaeyoung; Jung, Mooncheong; Yu, Sangseok; Yi, Sun

    2016-01-01

    In this study, a model reference adaptive controller is developed to regulate the outlet air flow rate of centrifugal compressor for automotive supercharger. The centrifugal compressor is developed using the analytical based method to predict the transient behavior of operating and the designed model is validated with experimental data to confirm the system accuracy. The model reference adaptive control structure consists of a compressor model and a MRAC(model reference adaptive control) mechanism. The feedback control do not robust with variation of system parameter but the applied adaptive control is robust even if the system parameter is changed. As a result, the MRAC was regulated to reference air flow rate. Also MRAC was found to be more robust control compared with the feedback control even if the system parameter is changed.

  18. Model Reference Adaptive Control of the Air Flow Rate of Centrifugal Compressor Using State Space Method

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jaeyoung; Jung, Mooncheong; Yu, Sangseok [Chungnam Nat’l Univ., Daejeon (Korea, Republic of); Yi, Sun [North Carolina A and T State Univ., Raleigh (United States)

    2016-08-15

    In this study, a model reference adaptive controller is developed to regulate the outlet air flow rate of centrifugal compressor for automotive supercharger. The centrifugal compressor is developed using the analytical based method to predict the transient behavior of operating and the designed model is validated with experimental data to confirm the system accuracy. The model reference adaptive control structure consists of a compressor model and a MRAC(model reference adaptive control) mechanism. The feedback control do not robust with variation of system parameter but the applied adaptive control is robust even if the system parameter is changed. As a result, the MRAC was regulated to reference air flow rate. Also MRAC was found to be more robust control compared with the feedback control even if the system parameter is changed.

  19. 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.

  20. Effect of dose-rate on the frequency of X-linked lethal mutation in the nematode Panagrellus redivivus

    International Nuclear Information System (INIS)

    Ager, D.

    1984-01-01

    A total X-ray dose of 50 Gy was applied to the nematode Panagrellus redivivus using dose-rates ranging from 0.23 Gy/min to 10.49 Gy/min, and the frequency of lethal X-chromosomes was determined. This frequency ranged from approximately 1.6% at the lower dose-rate to 4.3% at the highest dose-rate, indicating a dose-rate dependency of mutation frequency in the spermatogonia and oogonia of this organism. (orig.)

  1. 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.

  2. A consideration of two biochemical approaches to monitoring human populations for a change in germ cell mutation rates

    International Nuclear Information System (INIS)

    Neel, J.V.; Mohrenweiser, H.; Satoh, Chiyoko; Hamilton, H.B.

    1978-10-01

    This report presents two different strategies for monitoring increased mutation rates resulting from exposure to an environmental mutagen, both of which are based on the detection of biochemical variants of polypeptides. Using the first strategy, one monitors a defined population continuously for the rate at which children with such a variant are born to normal parents. An increase in this rate implies increasing exposure to a mutagen. With the second strategy, one contrasts the findings in the children born to a control group or groups with the findings in the children born to an exposed group, however this is defined. An example of each strategy is included. The alternatives to mutation which must be considered when a child with a variant is found to have nonaffected parents are considered. The numbers of individuals necessary to detect an increase of a specified magnitude are discussed. (author)

  3. 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.

  4. Adaptation of soybeans to northern climatic conditions and modern harvesting technique by mutation breeding

    International Nuclear Information System (INIS)

    Krausse, G.W.

    1990-01-01

    Full text: For growing soybean in northern countries early ripening and cold tolerant varieties with stable yield are necessary. For combine harvesting these varieties have to have a sufficient plant length and the insertion height of the lower pods has to be high. Two directions were followed in mutation breeding: After mutagenic treatment of middle late, highly productive, long-stalked initial varieties (as for instance 'Maple Arrow') early ripening mutants were searched for. On the other hand, the extremely early ripening, but too short-stalked 'Fiskeby V' was the initial variety for selecting long-stalked mutants with higher insertion of the lowest pods. Methyl-nitrosourea, sodium azide (0,5...2 mM) or γ-rays (50...250 Gy) served as mutagens. In the period 1979-1987 the following quantities of material have been dealt with: 11 initial varieties, 356000 treated seeds, 38000 progeny rows (= 736,000 plants) in M 2 , 5519 lines in M 3 , 557 lines in M 4 and 226 lines in M 5 . Vegetation period of early mutants was 3-8 days shorter, grain yield being the same or slightly increased. Extremely early ripening mutants showed strong yield depression. These mutants are still not suitable for growing in the GDR, because they ripen only in October but they are used as crossing parents and tested in warmer regions. The induction and selection of long-stalked mutants with higher insertion of the lowest pods in the early ripening Swedish variety 'Fiskeby V' led to the release of a mutant variety 'Dorado' in 1988. Further mutants with a yield potential of 1,5-2 t/ha are tested in official trials. (author)

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

    Science.gov (United States)

    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.

  6. Improvement of mutation rate and reduction of somatic effects by double treatment of chemical mutagens in barley

    International Nuclear Information System (INIS)

    Koo, B.C.; Maluszynski, M.

    1996-01-01

    Mutation techniques inducing more useful mutations and reducing somatic effects need to be improved for crop breeding. Seeds of barley varieties; Dema, Grosso were treated with two types of mutagens; 1) chemical treatment: single treatment or double treatment of two mutagens (N-nitroso-N-methylurea ; MNH, Sodium Azide; NaN 3 ) 2) gamma ray irradiation treatment. After treatment, half of seeds were used for germination test and half of seeds were sown to the field. With the higher dose of mutagen both chemical and gamma ray were plants treated, the higher rate of growth reduction rate was in M 1 seedling. In chemical treatment, germination rate of seeds, growth rate of coleoptile and root in double treatment of chemical mutagens were better than single treatments, especially in same dose. Growth inhibition rate of plant in double treatment of 1.0 mM MNH (0.5 mM MNH + 0.5 mM MNH), for example, were less than one of plants of single treatment of 1.0 mM MNH in pot and petri dish test. Growth reduction rate of culm and fertility rate in M 1 plants double treated in same dose of single treatment were also less than single one. With the higher dose of mutagen both chemical and gamma ray were plants treated, the higher frequency of chlorophyll mutants was in M 2 seedling. The rate of chlorophyll mutants in double treatment of chemical mutagens were higher than single treatment. Double treatment methods can be a improved method for induction of new good mutants, which were induced more useful mutations and reduced harmful somatic effects

  7. Influence of radiation exposure rate on somatic mutation frequency and loss of reproductive integrity in tradescantia stamen hairs

    International Nuclear Information System (INIS)

    Ichikawa, S.; Nauman, C.H.; Sparrow, A.H.; Takahashi, C.S.

    1978-01-01

    Inflorescences of Tradescantia clone 02 (2n=12), hetero- or hemi-zygous for flower color, were exposed to a series of γ-ray exposures at two different exposure rates, 29.3 R/min and 0.026-0.52 R/min. Pink mutation-response curves, and survival curves based on reproductive integrity, were constructed for each of the exposure rates. Loss of reproductive integrity was also assessed at high (256 R/min) and low (0.52-4.17 R/min) γ-ray exposure rates in T. blossfeldiana (2n=72). All observations were made on stamen hairs. The higher exposure rate was 1.3-1.7 times more effective in inducing pink mutations in clone 02. A greater efficiency of the higher exposure rate was also found for both taxa at the loss of reproductive integrity endpoint. The D 0 values obtained at the higher exposure rates, 154 R for clone 02 and 720 R for T. blossfeldiana, were significantly lower than the corresponding values of 270 R and 1880 R obtained at the lower exposure rates. These D 0 's differ by factors of 1.75 and 2.61 for clone 02 and T. blossfeldiana, respectively. D 0 's for the two taxa were found to be inversely correlated with their interphase chromosome volumes. (Auth.)

  8. Transcription Restores DNA Repair to Heterochromatin, Determining Regional Mutation Rates in Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Christina L. Zheng

    2014-11-01

    Full Text Available Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER, thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.

  9. Germline mutation rates in families residing in high level natural radiation areas of Kerala coast in southwest India

    International Nuclear Information System (INIS)

    Das, Birajalaxmi; Ghosh, Anu; Ahmad, Shazia; Saini, DivyaIakshmi; Chauhan, P.S.; Seshadri, M.

    2010-01-01

    For this study, 200 nuclear families have been analyzed using over 40 mini- and microsatellite markers. Cord blood samples for the child and peripheral blood samples for the parent(s) were collected in EDTA vacuutainers from the hospital units located in High Level Natural Radiation Areas (HLNRA) and Normal Level Natural Radiation Areas (NLNRA). Both the parents of the newborn were exposed to the background dose. The families were grouped into four distinct dose groups - NLNRA group 5.00 mGy/year. An overall mutation rate of 2.08 X 10 -3 per cell per generation was observed for NLNRA and 2.12 X 10 -3 per cell per generation for HLNRA families. No radiation induced dose response was observed for the stratified groups. Thus, this study shows that mutation rates at mini- and microsatellites in the off springs of the parents living in the high background radiation areas of Kerala does not vary with radiation exposure. This is the first report to understand germline mutation rates at hypervariable loci in families residing in high level natural radiation areas of the world

  10. Adaptive rate selection scheme for video transmission to resolve IEEE 802.11 performance anomaly

    Science.gov (United States)

    Tang, Guijin; Zhu, Xiuchang

    2011-10-01

    Multi-rate transmission may lead to performance anomaly in an IEEE 802.11 network. It will decrease the throughputs of all the higher rate stations. This paper proposes an adaptive rate selection scheme for video service when performance anomaly occurs. Considering that video has the characteristic of tolerance to packet loss, we actively drop several packets so as to select the rates as high as possible for transmitting packets. Experiment shows our algorithm can decrease the delay and jitter of video, and improve the system throughput as well.

  11. Cross-layer optimized rate adaptation and scheduling for multiple-user wireless video streaming

    NARCIS (Netherlands)

    Ozcelebi, T.; Sunay, M.O.; Tekalp, A.M.; Civanlar, M.R.

    2007-01-01

    We present a cross-layer optimized video rate adaptation and user scheduling scheme for multi-user wireless video streaming aiming for maximum quality of service (QoS) for each user,, maximum system video throughput, and QoS fairness among users. These objectives are jointly optimized using a

  12. Modeling the time--varying subjective quality of HTTP video streams with rate adaptations.

    Science.gov (United States)

    Chen, Chao; Choi, Lark Kwon; de Veciana, Gustavo; Caramanis, Constantine; Heath, Robert W; Bovik, Alan C

    2014-05-01

    Newly developed hypertext transfer protocol (HTTP)-based video streaming technologies enable flexible rate-adaptation under varying channel conditions. Accurately predicting the users' quality of experience (QoE) for rate-adaptive HTTP video streams is thus critical to achieve efficiency. An important aspect of understanding and modeling QoE is predicting the up-to-the-moment subjective quality of a video as it is played, which is difficult due to hysteresis effects and nonlinearities in human behavioral responses. This paper presents a Hammerstein-Wiener model for predicting the time-varying subjective quality (TVSQ) of rate-adaptive videos. To collect data for model parameterization and validation, a database of longer duration videos with time-varying distortions was built and the TVSQs of the videos were measured in a large-scale subjective study. The proposed method is able to reliably predict the TVSQ of rate adaptive videos. Since the Hammerstein-Wiener model has a very simple structure, the proposed method is suitable for online TVSQ prediction in HTTP-based streaming.

  13. Transition from positive to neutral in mutation fixation along with continuing rising fitness in thermal adaptive evolution.

    Science.gov (United States)

    Kishimoto, Toshihiko; Iijima, Leo; Tatsumi, Makoto; Ono, Naoaki; Oyake, Ayana; Hashimoto, Tomomi; Matsuo, Moe; Okubo, Masato; Suzuki, Shingo; Mori, Kotaro; Kashiwagi, Akiko; Furusawa, Chikara; Ying, Bei-Wen; Yomo, Tetsuya

    2010-10-21

    It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution.

  14. Activity and heart rate in semi-domesticated reindeer during adaptation to emergency feeding.

    Science.gov (United States)

    Nilsson, A; Ahman, B; Norberg, H; Redbo, I; Eloranta, E; Olsson, K

    2006-06-15

    Although reindeer are well adapted to limited food resources during winter, semi-domesticated reindeer are regularly fed when snow conditions are bad in order to prevent starvation. Feeding sometimes results in health problems and loss of animals. This study was made to assess if activity pattern in reindeer could be used as a tool for the reindeer herder in early detection of animals that are not adapting to feeding. The frequency of 10 behavioural categories was recorded in five groups of penned, eight-month-old, female semi-domesticated reindeer. Three reindeer per group were fitted with heart rate monitors. Lying was the most frequent behaviour, whilst there were few cases of agonistic behaviour. Heart rate varied during the day, with peaks during feeding and low heart rates in the early morning. Restricted feed intake resulted in more locomotion and seeking but less ruminating compared to feeding ad libitum. This was followed by a generally lower heart rate in reindeer in the restricted groups compared to controls. Subsequent feeding with different combinations of lichens, silage and pellets ad libitum resulted initially in significantly more of the animals lying curled up, compared to controls, combined with increased heart rates. As the experiment continued the general activity pattern, as well as the heart rate, gradually became more similar in all groups. Lying curled was the behavioural indicator most consistently affected by feed deprivation and adaptation to feeding and may thus be a useful indicator to distinguish individual reindeer that are not adjusting to feeding.

  15. A reduced amino acid alphabet for understanding and designing protein adaptation to mutation.

    Science.gov (United States)

    Etchebest, C; Benros, C; Bornot, A; Camproux, A-C; de Brevern, A G

    2007-11-01

    Protein sequence world is considerably larger than structure world. In consequence, numerous non-related sequences may adopt similar 3D folds and different kinds of amino acids may thus be found in similar 3D structures. By grouping together the 20 amino acids into a smaller number of representative residues with similar features, sequence world simplification may be achieved. This clustering hence defines a reduced amino acid alphabet (reduced AAA). Numerous works have shown that protein 3D structures are composed of a limited number of building blocks, defining a structural alphabet. We previously identified such an alphabet composed of 16 representative structural motifs (5-residues length) called Protein Blocks (PBs). This alphabet permits to translate the structure (3D) in sequence of PBs (1D). Based on these two concepts, reduced AAA and PBs, we analyzed the distributions of the different kinds of amino acids and their equivalences in the structural context. Different reduced sets were considered. Recurrent amino acid associations were found in all the local structures while other were specific of some local structures (PBs) (e.g Cysteine, Histidine, Threonine and Serine for the alpha-helix Ncap). Some similar associations are found in other reduced AAAs, e.g Ile with Val, or hydrophobic aromatic residues Trp with Phe and Tyr. We put into evidence interesting alternative associations. This highlights the dependence on the information considered (sequence or structure). This approach, equivalent to a substitution matrix, could be useful for designing protein sequence with different features (for instance adaptation to environment) while preserving mainly the 3D fold.

  16. Layer-based buffer aware rate adaptation design for SHVC video streaming

    Science.gov (United States)

    Gudumasu, Srinivas; Hamza, Ahmed; Asbun, Eduardo; He, Yong; Ye, Yan

    2016-09-01

    This paper proposes a layer based buffer aware rate adaptation design which is able to avoid abrupt video quality fluctuation, reduce re-buffering latency and improve bandwidth utilization when compared to a conventional simulcast based adaptive streaming system. The proposed adaptation design schedules DASH segment requests based on the estimated bandwidth, dependencies among video layers and layer buffer fullness. Scalable HEVC video coding is the latest state-of-art video coding technique that can alleviate various issues caused by simulcast based adaptive video streaming. With scalable coded video streams, the video is encoded once into a number of layers representing different qualities and/or resolutions: a base layer (BL) and one or more enhancement layers (EL), each incrementally enhancing the quality of the lower layers. Such layer based coding structure allows fine granularity rate adaptation for the video streaming applications. Two video streaming use cases are presented in this paper. The first use case is to stream HD SHVC video over a wireless network where available bandwidth varies, and the performance comparison between proposed layer-based streaming approach and conventional simulcast streaming approach is provided. The second use case is to stream 4K/UHD SHVC video over a hybrid access network that consists of a 5G millimeter wave high-speed wireless link and a conventional wired or WiFi network. The simulation results verify that the proposed layer based rate adaptation approach is able to utilize the bandwidth more efficiently. As a result, a more consistent viewing experience with higher quality video content and minimal video quality fluctuations can be presented to the user.

  17. The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic.

    Science.gov (United States)

    Heath, Kathleen M; Axton, Jacob H; McCullough, John M; Harris, Nathan

    2016-05-01

    The C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronutrient for effective thermoregulation. We argue that the C282Y allele was an adaptation to this novel environment. To address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis. Our findings indicate that the geographic cline for C282Y frequency in Europe increases as average temperatures decrease below 16°C, a critical threshold for thermoregulation, with rainy days intensifying the trend. The results indicate that the deleterious C282Y allele, responsible for most cases of hemochromatosis, may have evolved as a selective advantage to culture and climate during the European Neolithic. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

  18. Early and late rate of force development: differential adaptive responses to resistance training?

    DEFF Research Database (Denmark)

    Andersen, L L; Andersen, Jesper Løvind; Zebis, M K

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....... males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from...

  19. The role of weak selection and high mutation rates in nearly neutral evolution.

    Science.gov (United States)

    Lawson, Daniel John; Jensen, Henrik Jeldtoft

    2009-04-21

    Neutral dynamics occur in evolution if all types are 'effectively equal' in their reproductive success, where the definition of 'effectively equal' depends on the population size and the details of mutations. Empirically observed neutral genetic evolution in extremely large clonal populations can only be explained under current models if selection is completely absent. Such models typically consider the case where population dynamics occurs on a different timescale to evolution. However, this assumption is invalid when mutations are not rare in a whole population. We show that this has important consequences for the occurrence of neutral evolution in clonal populations. In highly connected type spaces, neutral dynamics can occur for all population sizes despite significant selective differences, via the forming of effectively neutral networks connecting rare neutral types. Biological implications include an explanation for the high diversity of rare types that survive in large clonal populations, and a theoretical justification for the use of neutral null models.

  20. A Site Specific Model And Analysis Of The Neutral Somatic Mutation Rate In Whole-Genome Cancer Data

    DEFF Research Database (Denmark)

    Bertl, Johanna; Guo, Qianyun; Rasmussen, Malene Juul

    2017-01-01

    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 ra...

  1. Large-scale analyses of synonymous substitution rates can be sensitive to assumptions about the process of mutation.

    Science.gov (United States)

    Aris-Brosou, Stéphane; Bielawski, Joseph P

    2006-08-15

    A popular approach to examine the roles of mutation and selection in the evolution of genomes has been to consider the relationship between codon bias and synonymous rates of molecular evolution. A significant relationship between these two quantities is taken to indicate the action of weak selection on substitutions among synonymous codons. The neutral theory predicts that the rate of evolution is inversely related to the level of functional constraint. Therefore, selection against the use of non-preferred codons among those coding for the same amino acid should result in lower rates of synonymous substitution as compared with sites not subject to such selection pressures. However, reliably measuring the extent of such a relationship is problematic, as estimates of synonymous rates are sensitive to our assumptions about the process of molecular evolution. Previous studies showed the importance of accounting for unequal codon frequencies, in particular when synonymous codon usage is highly biased. Yet, unequal codon frequencies can be modeled in different ways, making different assumptions about the mutation process. Here we conduct a simulation study to evaluate two different ways of modeling uneven codon frequencies and show that both model parameterizations can have a dramatic impact on rate estimates and affect biological conclusions about genome evolution. We reanalyze three large data sets to demonstrate the relevance of our results to empirical data analysis.

  2. Rate Adaptation Based on Collision Probability for IEEE 802.11 WLANs

    Science.gov (United States)

    Kim, Taejoon; Lim, Jong-Tae

    Nowadays IEEE 802.11 wireless local area networks (WLANs) support multiple transmission rates. To achieve the best performance, transmitting stations adopt the various forms of automatic rate fallback (ARF). However, ARF suffers from severe performance degradation as the number of transmitting stations increases. In this paper, we propose a new rate adaptation scheme which adjusts the ARF's up/down threshold according to the channel contention level. Simulation result shows that the proposed scheme achieves fairly good performance compared with the existing schemes.

  3. High speed and adaptable error correction for megabit/s rate quantum key distribution.

    Science.gov (United States)

    Dixon, A R; Sato, H

    2014-12-02

    Quantum Key Distribution is moving from its theoretical foundation of unconditional security to rapidly approaching real world installations. A significant part of this move is the orders of magnitude increases in the rate at which secure key bits are distributed. However, these advances have mostly been confined to the physical hardware stage of QKD, with software post-processing often being unable to support the high raw bit rates. In a complete implementation this leads to a bottleneck limiting the final secure key rate of the system unnecessarily. Here we report details of equally high rate error correction which is further adaptable to maximise the secure key rate under a range of different operating conditions. The error correction is implemented both in CPU and GPU using a bi-directional LDPC approach and can provide 90-94% of the ideal secure key rate over all fibre distances from 0-80 km.

  4. High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing

    DEFF Research Database (Denmark)

    Martin, P; Heiskari, N; Zhou, J

    1998-01-01

    -amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining...

  5. Training adaptation and heart rate variability in elite endurance athletes: opening the door to effective monitoring.

    Science.gov (United States)

    Plews, Daniel J; Laursen, Paul B; Stanley, Jamie; Kilding, Andrew E; Buchheit, Martin

    2013-09-01

    The measurement of heart rate variability (HRV) is often considered a convenient non-invasive assessment tool for monitoring individual adaptation to training. Decreases and increases in vagal-derived indices of HRV have been suggested to indicate negative and positive adaptations, respectively, to endurance training regimens. However, much of the research in this area has involved recreational and well-trained athletes, with the small number of studies conducted in elite athletes revealing equivocal outcomes. For example, in elite athletes, studies have revealed both increases and decreases in HRV to be associated with negative adaptation. Additionally, signs of positive adaptation, such as increases in cardiorespiratory fitness, have been observed with atypical concomitant decreases in HRV. As such, practical ways by which HRV can be used to monitor training status in elites are yet to be established. This article addresses the current literature that has assessed changes in HRV in response to training loads and the likely positive and negative adaptations shown. We reveal limitations with respect to how the measurement of HRV has been interpreted to assess positive and negative adaptation to endurance training regimens and subsequent physical performance. We offer solutions to some of the methodological issues associated with using HRV as a day-to-day monitoring tool. These include the use of appropriate averaging techniques, and the use of specific HRV indices to overcome the issue of HRV saturation in elite athletes (i.e., reductions in HRV despite decreases in resting heart rate). Finally, we provide examples in Olympic and World Champion athletes showing how these indices can be practically applied to assess training status and readiness to perform in the period leading up to a pinnacle event. The paper reveals how longitudinal HRV monitoring in elites is required to understand their unique individual HRV fingerprint. For the first time, we demonstrate how

  6. Channel allocation and rate adaptation for relayed transmission over correlated fading channels

    KAUST Repository

    Hwang, Kyusung

    2009-09-01

    We consider, in this paper, channel allocation and rate adaptation scheme for relayed transmission over correlated fading channels via cross-layer design. Specifically, jointly considering the data link layer buffer occupancy and channel quality at both the source and relay nodes, we develop an optimal channel allocation and rate adaptation policy for a dual-hop relayed transmission. As such the overall transmit power for the relayed system is minimized while a target packet dropping rate (PDR) due to buffer over flows is guaranteed. In order to find such an optimal policy, the channel allocation and rate adaptation transmission framework is formulated as a constraint Markov decision process (CMDP). The PDR performance of the optimal policy is compared with that of two conventional suboptimal schemes, namely the channel quality based and the buffer occupancy based channel allocation schemes. Numerical results show that for a given power budget, the optimal scheme requires significantly less power than the conventional schemes in order to maintain a target PDR. ©2009 IEEE.

  7. High mutation rates explain low population genetic divergence at copy-number-variable loci in Homo sapiens.

    Science.gov (United States)

    Hu, Xin-Sheng; Yeh, Francis C; Hu, Yang; Deng, Li-Ting; Ennos, Richard A; Chen, Xiaoyang

    2017-02-22

    Copy-number-variable (CNV) loci differ from single nucleotide polymorphic (SNP) sites in size, mutation rate, and mechanisms of maintenance in natural populations. It is therefore hypothesized that population genetic divergence at CNV loci will differ from that found at SNP sites. Here, we test this hypothesis by analysing 856 CNV loci from the genomes of 1184 healthy individuals from 11 HapMap populations with a wide range of ancestry. The results show that population genetic divergence at the CNV loci is generally more than three times lower than at genome-wide SNP sites. Populations generally exhibit very small genetic divergence (G st  = 0.05 ± 0.049). The smallest divergence is among African populations (G st  = 0.0081 ± 0.0025), with increased divergence among non-African populations (G st  = 0.0217 ± 0.0109) and then among African and non-African populations (G st  = 0.0324 ± 0.0064). Genetic diversity is high in African populations (~0.13), low in Asian populations (~0.11), and intermediate in the remaining 11 populations. Few significant linkage disequilibria (LDs) occur between the genome-wide CNV loci. Patterns of gametic and zygotic LDs indicate the absence of epistasis among CNV loci. Mutation rate is about twice as large as the migration rate in the non-African populations, suggesting that the high mutation rates play dominant roles in producing the low population genetic divergence at CNV loci.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Whole-body calcium flux rates in cichlid teleost fish Oreochromis mossambicus adapted to freshwater

    International Nuclear Information System (INIS)

    Flik, G.; Fenwick, J.C.; Kolar, Z.; Mayer-Gostan, N.; Wendelaar Bonga, S.E.

    1985-01-01

    Radiotracer techniques were used to measure influx and efflux rates of Ca 2+ in freshwater-adapted Oreochromis mossambicus. The influx rate of Ca 2+ is related to body weight (W) as Fin = 50W0.805 nmol Ca 2+ /h. For a 20-g fish the calculated influx rate was 558 nmol Ca 2+ /h, and this was attributed largely to extraintestinal uptake since the drinking rate was estimated to be only 28 microliter water/h, which corresponds to an intake of 22.4 nmol Ca 2+ /h. The Ca 2+ efflux rate was calculated using the initial rate of appearance of radiotracer in the ambient water and the specific activity of plasma Ca 2+ . Tracer efflux rates were constant over 6-8 h, which indicated that there was no substantial loss of tracer in either the urine or the feces because this would have resulted in random bursts of tracer loss. Efflux rates then primarily represent integumentary and presumably branchial efflux rates. The efflux rate of Ca 2+ is related to body weight as Fout = 30W0.563 nmol Ca 2+ /h, which means an efflux rate of 162 nmol Ca 2+ /h for a 20-g fish. The net whole-body Ca 2+ influx, calculated as Fnet = Fin - Fout, was 396 nmol/h for a 20-g fish, which proves that the ambient water is an important source of Ca 2+

  11. Adaptive sampling rate control for networked systems based on statistical characteristics of packet disordering.

    Science.gov (United States)

    Li, Jin-Na; Er, Meng-Joo; Tan, Yen-Kheng; Yu, Hai-Bin; Zeng, Peng

    2015-09-01

    This paper investigates an adaptive sampling rate control scheme for networked control systems (NCSs) subject to packet disordering. The main objectives of the proposed scheme are (a) to avoid heavy packet disordering existing in communication networks and (b) to stabilize NCSs with packet disordering, transmission delay and packet loss. First, a novel sampling rate control algorithm based on statistical characteristics of disordering entropy is proposed; secondly, an augmented closed-loop NCS that consists of a plant, a sampler and a state-feedback controller is transformed into an uncertain and stochastic system, which facilitates the controller design. Then, a sufficient condition for stochastic stability in terms of Linear Matrix Inequalities (LMIs) is given. Moreover, an adaptive tracking controller is designed such that the sampling period tracks a desired sampling period, which represents a significant contribution. Finally, experimental results are given to illustrate the effectiveness and advantages of the proposed scheme. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Chaos Synchronization Using Adaptive Dynamic Neural Network Controller with Variable Learning Rates

    Directory of Open Access Journals (Sweden)

    Chih-Hong Kao

    2011-01-01

    Full Text Available This paper addresses the synchronization of chaotic gyros with unknown parameters and external disturbance via an adaptive dynamic neural network control (ADNNC system. The proposed ADNNC system is composed of a neural controller and a smooth compensator. The neural controller uses a dynamic RBF (DRBF network to online approximate an ideal controller. The DRBF network can create new hidden neurons online if the input data falls outside the hidden layer and prune the insignificant hidden neurons online if the hidden neuron is inappropriate. The smooth compensator is designed to compensate for the approximation error between the neural controller and the ideal controller. Moreover, the variable learning rates of the parameter adaptation laws are derived based on a discrete-type Lyapunov function to speed up the convergence rate of the tracking error. Finally, the simulation results which verified the chaotic behavior of two nonlinear identical chaotic gyros can be synchronized using the proposed ADNNC scheme.

  13. Rate-adaptive BCH coding for Slepian-Wolf coding of highly correlated sources

    DEFF Research Database (Denmark)

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

    2012-01-01

    This paper considers using BCH codes for distributed source coding using feedback. The focus is on coding using short block lengths for a binary source, X, having a high correlation between each symbol to be coded and a side information, Y, such that the marginal probability of each symbol, Xi in X......, given Y is highly skewed. In the analysis, noiseless feedback and noiseless communication are assumed. A rate-adaptive BCH code is presented and applied to distributed source coding. Simulation results for a fixed error probability show that rate-adaptive BCH achieves better performance than LDPCA (Low......-Density Parity-Check Accumulate) codes for high correlation between source symbols and the side information....

  14. Tracking Control of Hysteretic Piezoelectric Actuator using Adaptive Rate-Dependent Controller.

    Science.gov (United States)

    Tan, U-Xuan; Latt, Win Tun; Widjaja, Ferdinan; Shee, Cheng Yap; Riviere, Cameron N; Ang, Wei Tech

    2009-03-16

    With the increasing popularity of actuators involving smart materials like piezoelectric, control of such materials becomes important. The existence of the inherent hysteretic behavior hinders the tracking accuracy of the actuators. To make matters worse, the hysteretic behavior changes with rate. One of the suggested ways is to have a feedforward controller to linearize the relationship between the input and output. Thus, the hysteretic behavior of the actuator must first be modeled by sensing the relationship between the input voltage and output displacement. Unfortunately, the hysteretic behavior is dependent on individual actuator and also environmental conditions like temperature. It is troublesome and costly to model the hysteresis regularly. In addition, the hysteretic behavior of the actuators also changes with age. Most literature model the actuator using a cascade of rate-independent hysteresis operators and a dynamical system. However, the inertial dynamics of the structure is not the only contributing factor. A complete model will be complex. Thus, based on the studies done on the phenomenological hysteretic behavior with rate, this paper proposes an adaptive rate-dependent feedforward controller with Prandtl-Ishlinskii (PI) hysteresis operators for piezoelectric actuators. This adaptive controller is achieved by adapting the coefficients to manipulate the weights of the play operators. Actual experiments are conducted to demonstrate the effectiveness of the adaptive controller. The main contribution of this paper is its ability to perform tracking control of non-periodic motion and is illustrated with the tracking control ability of a couple of different non-periodic waveforms which were created by passing random numbers through a low pass filter with a cutoff frequency of 20Hz.

  15. Conventional to Cloud: Detailed survey and comparative study of multimedia streaming rate Adaptation

    OpenAIRE

    Selvaraj Kesavan; Jayakumar J

    2014-01-01

    Infotainment and telecommunication industry is fast evolving towards personalized network connectivity and newer applications services ranging from music playback to ever changing telephony applications. Streaming is the key services which enables the users to view real time multimedia content on-the-go anywhere and everywhere. In streaming, quality of service is a major concern in the increasing network traffic and high user demand. Rate adaptation is crucial process to dynamically evaluate,...

  16. Adaptive Mean Queue Size and Its Rate of Change: Queue Management with Random Dropping

    OpenAIRE

    Karmeshu; Patel, Sanjeev; Bhatnagar, Shalabh

    2016-01-01

    The Random early detection (RED) active queue management (AQM) scheme uses the average queue size to calculate the dropping probability in terms of minimum and maximum thresholds. The effect of heavy load enhances the frequency of crossing the maximum threshold value resulting in frequent dropping of the packets. An adaptive queue management with random dropping (AQMRD) algorithm is proposed which incorporates information not just about the average queue size but also the rate of change of th...

  17. 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

  18. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

    NARCIS (Netherlands)

    Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; van der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; Ausems, M.G.E.M.; Hoogerbrugge, N.; van Asperen, C.J.; Gómez García, E.B.; Meijers-Heijboer, H.; ten Kate, L.P.; Menko, F.H.; van 't Veer, L.J.

    2010-01-01

    Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria

  19. Adaptation to environmental temperature is a major determinant of molecular evolutionary rates in archaea.

    Science.gov (United States)

    Groussin, Mathieu; Gouy, Manolo

    2011-09-01

    Methods to infer the ancestral conditions of life are commonly based on geological and paleontological analyses. Recently, several studies used genome sequences to gain information about past ecological conditions taking advantage of the property that the G+C and amino acid contents of bacterial and archaeal ribosomal DNA genes and proteins, respectively, are strongly influenced by the environmental temperature. The adaptation to optimal growth temperature (OGT) since the Last Universal Common Ancestor (LUCA) over the universal tree of life was examined, and it was concluded that LUCA was likely to have been a mesophilic organism and that a parallel adaptation to high temperature occurred independently along the two lineages leading to the ancestors of Bacteria on one side and of Archaea and Eukarya on the other side. Here, we focus on Archaea to gain a precise view of the adaptation to OGT over time in this domain. It has been often proposed on the basis of indirect evidence that the last archaeal common ancestor was a hyperthermophilic organism. Moreover, many results showed the influence of environmental temperature on the evolutionary dynamics of archaeal genomes: Thermophilic organisms generally display lower evolutionary rates than mesophiles. However, to our knowledge, no study tried to explain the differences of evolutionary rates for the entire archaeal domain and to investigate the evolution of substitution rates over time. A comprehensive archaeal phylogeny and a non homogeneous model of the molecular evolutionary process allowed us to estimate ancestral base and amino acid compositions and OGTs at each internal node of the archaeal phylogenetic tree. The last archaeal common ancestor is predicted to have been hyperthermophilic and adaptations to cooler environments can be observed for extant mesophilic species. Furthermore, mesophilic species present both long branches and high variation of nucleotide and amino acid compositions since the last archaeal

  20. Induce mutations and adaptation

    International Nuclear Information System (INIS)

    Borojevicj, K.

    1987-01-01

    The effect of wheat irradiation has been studied through 20 generations. Radiation had deleterious effect in the year of treatment which genetic effect was traceable even 20 generations after treatment. (author). 11 refs.; 2 figs

  1. Maximum type 1 error rate inflation in multiarmed clinical trials with adaptive interim sample size modifications.

    Science.gov (United States)

    Graf, Alexandra C; Bauer, Peter; Glimm, Ekkehard; Koenig, Franz

    2014-07-01

    Sample size modifications in the interim analyses of an adaptive design can inflate the type 1 error rate, if test statistics and critical boundaries are used in the final analysis as if no modification had been made. While this is already true for designs with an overall change of the sample size in a balanced treatment-control comparison, the inflation can be much larger if in addition a modification of allocation ratios is allowed as well. In this paper, we investigate adaptive designs with several treatment arms compared to a single common control group. Regarding modifications, we consider treatment arm selection as well as modifications of overall sample size and allocation ratios. The inflation is quantified for two approaches: a naive procedure that ignores not only all modifications, but also the multiplicity issue arising from the many-to-one comparison, and a Dunnett procedure that ignores modifications, but adjusts for the initially started multiple treatments. The maximum inflation of the type 1 error rate for such types of design can be calculated by searching for the "worst case" scenarios, that are sample size adaptation rules in the interim analysis that lead to the largest conditional type 1 error rate in any point of the sample space. To show the most extreme inflation, we initially assume unconstrained second stage sample size modifications leading to a large inflation of the type 1 error rate. Furthermore, we investigate the inflation when putting constraints on the second stage sample sizes. It turns out that, for example fixing the sample size of the control group, leads to designs controlling the type 1 error rate. © 2014 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Paternal Age Explains a Major Portion of De Novo Germline Mutation Rate Variability in Healthy Individuals.

    Directory of Open Access Journals (Sweden)

    Simon L Girard

    Full Text Available De novo mutations (DNM are an important source of rare variants and are increasingly being linked to the development of many diseases. Recently, the paternal age effect has been the focus of a number of studies that attempt to explain the observation that increasing paternal age increases the risk for a number of diseases. Using disease-free familial quartets we show that there is a strong positive correlation between paternal age and germline DNM in healthy subjects. We also observed that germline CNVs do not follow the same trend, suggesting a different mechanism. Finally, we observed that DNM were not evenly distributed across the genome, which adds support to the existence of DNM hotspots.

  3. 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.

  4. Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion.

    Directory of Open Access Journals (Sweden)

    Robert D Lagow

    2007-04-01

    Full Text Available Both constitutive secretion and Ca(2+-regulated exocytosis require the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show that a mutation modifying a hydrophobic layer in syntaxin 1A regulates the rate of vesicle fusion. Syntaxin 1A molecules share a highly conserved threonine in the C-terminal +7 layer near the transmembrane domain. Mutation of this threonine to isoleucine results in a structural change that more closely resembles those found in syntaxins ascribed to the constitutive secretory pathway. Flies carrying the I254 mutant protein have increased levels of SNARE complexes and dramatically enhanced rate of both constitutive and evoked vesicle fusion. In contrast, overexpression of the T254 wild-type protein in neurons reduces vesicle fusion only in the I254 mutant background. These results are consistent with molecular dynamics simulations of the SNARE core complex, suggesting that T254 serves as an internal brake to dampen SNARE zippering and impede vesicle fusion, whereas I254 favors fusion by enhancing intermolecular interaction within the SNARE core complex.

  5. Radiation-induced dominant skeletal mutations in mice: mutation rate, characteristics, and usefulness in estimating genetic hazard to humans from radiation

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    The work discussed in this paper represents a major advance in the difficult task of trying to estimate the effects that an increase in mutation frequency would have on human health. Male mice were bred to three females prior to being killed and skeleton studies made. Guidelines were instituted for checking progeny mutations. Surprising results showed a mutation frequency of 1.4% per gamete where none would have been expected. It is now clear that mice can be greatly deformed without showing external effects

  6. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  7. 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.

  8. Metabolic Alterations Caused by KRAS Mutations in Colorectal Cancer Contribute to Cell Adaptation to Glutamine Depletion by Upregulation of Asparagine Synthetase

    Directory of Open Access Journals (Sweden)

    Kosuke Toda

    2016-11-01

    Full Text Available A number of clinical trials have shown that KRAS mutations of colorectal cancer (CRC can predict a lack of responses to anti-epidermal growth factor receptor–based therapy. Recently, there have been several studies to elucidate metabolism reprogramming in cancer. However, it remains to be investigated how mutated KRAS can coordinate the metabolic shift to sustain CRC tumor growth. In this study, we found that KRAS mutation in CRC caused alteration in amino acid metabolism. KRAS mutation causes a marked decrease in aspartate level and an increase in asparagine level in CRC. Using several human CRC cell lines and clinical specimens of primary CRC, we demonstrated that the expression of asparagine synthetase (ASNS, an enzyme that synthesizes asparagine from aspartate, was upregulated by mutated KRAS and that ASNS expression was induced by KRAS-activated signaling pathway, in particular PI3K-AKT-mTOR pathway. Importantly, we demonstrated that KRAS-mutant CRC cells could become adaptive to glutamine depletion through asparagine biosynthesis by ASNS and that asparagine addition could rescue the inhibited growth and viability of cells grown under the glutamine-free condition in vitro. Notably, a pronounced growth suppression of KRAS-mutant CRC was observed upon ASNS knockdown in vivo. Furthermore, combination of L-asparaginase plus rapamycin markedly suppressed the growth of KRAS-mutant CRC xenografts in vivo, whereas either L-asparaginase or rapamycin alone was not effective. These results indicate ASNS might be a novel therapeutic target against CRCs with mutated KRAS.

  9. Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.

    Science.gov (United States)

    Dunn, Cory D

    2011-10-01

    Mitochondrial DNA (mtDNA) mutations escalate with increasing age in higher organisms. However, it has so far been difficult to experimentally determine whether mtDNA mutation merely correlates with age or directly limits lifespan. A recent study shows that budding yeast can also lose functional mtDNA late in life. Interestingly, independent studies of replicative lifespan (RLS) and of mtDNA-deficient cells show that the same mutations can increase both RLS and the division rate of yeast lacking the mitochondrial genome. These exciting, parallel findings imply a potential causal relationship between mtDNA mutation and replicative senescence. Furthermore, these results suggest more efficient methods for discovering genes that determine lifespan. Copyright © 2011 WILEY Periodicals, Inc.

  10. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    building skills, knowledge or networks on adaptation, ... the African partners leading the AfricaAdapt network, together with the UK-based Institute of Development Studies; and ... UNCCD Secretariat, Regional Coordination Unit for Africa, Tunis, Tunisia .... 26 Rural–urban Cooperation on Water Management in the Context of.

  11. Rate adaptive multilevel coded modulation with high coding gain in intensity modulation direct detection optical communication

    Science.gov (United States)

    Xiao, Fei; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Tian, Qinghua; Tian, Feng; Wang, Yongjun; Rao, Lan; Ullah, Rahat; Zhao, Feng; Li, Deng'ao

    2018-02-01

    A rate-adaptive multilevel coded modulation (RA-MLC) scheme based on fixed code length and a corresponding decoding scheme is proposed. RA-MLC scheme combines the multilevel coded and modulation technology with the binary linear block code at the transmitter. Bits division, coding, optional interleaving, and modulation are carried out by the preset rule, then transmitted through standard single mode fiber span equal to 100 km. The receiver improves the accuracy of decoding by means of soft information passing through different layers, which enhances the performance. Simulations are carried out in an intensity modulation-direct detection optical communication system using MATLAB®. Results show that the RA-MLC scheme can achieve bit error rate of 1E-5 when optical signal-to-noise ratio is 20.7 dB. It also reduced the number of decoders by 72% and realized 22 rate adaptation without significantly increasing the computing time. The coding gain is increased by 7.3 dB at BER=1E-3.

  12. Heart rate variability in the standing position reflects training adaptation in professional soccer players.

    Science.gov (United States)

    Ravé, Guillaume; Fortrat, Jacques-Olivier

    2016-08-01

    To show that heart rate variability (HRV) in the standing position better reflects the way in which athletes adapt to training in so-called intermittent sports than the indicator of resting parasympathetic tone usually employed in endurance sports. Twenty professional soccer players (intermittent sport) took part in a 5-week training session divided into three successive periods: "Warm-up", "Intensive training" and "Tapering". At the beginning and end of each of the three periods, a stand test was carried out and the heart rate was recorded, beat by beat (Polar Team 2). We analysed HRV to determine the indicator mostly used to demonstrate training adaptation in endurance sports (lnRMSSD supine, natural logarithm of root mean square of the successive differences) as well as indicators obtained by means of spectral analysis in both supine and standing position. A decrease in heart rate was observed in the supine position at rest during training (-5.2 ± 1.3 bpm) while lnRMSSD and spectral analysis indicators remained unchanged. The "Warm-up" caused an increase in spectral analysis total power in standing position which was further highlighted by "Tapering" (3.39 ± 0.09, 3.61 ± 0.08 and 3.65 ± 0.09 log ms(2), respectively). However, the autonomic changes are probably more complex than a change in autonomic activity or balance since spectral analysis autonomic indicators remained unchanged. HRV in the standing position could monitor training adaptation in intermittent sports contrary to the indicator usually employed in endurance sports. However, the significance of the HRV change in the standing position during training remains unclear.

  13. Experimental verification of preset time count rate meters based on adaptive digital signal processing algorithms

    Directory of Open Access Journals (Sweden)

    Žigić Aleksandar D.

    2005-01-01

    Full Text Available Experimental verifications of two optimized adaptive digital signal processing algorithms implemented in two pre set time count rate meters were per formed ac cording to appropriate standards. The random pulse generator realized using a personal computer, was used as an artificial radiation source for preliminary system tests and performance evaluations of the pro posed algorithms. Then measurement results for background radiation levels were obtained. Finally, measurements with a natural radiation source radioisotope 90Sr-90Y, were carried out. Measurement results, con ducted without and with radio isotopes for the specified errors of 10% and 5% showed to agree well with theoretical predictions.

  14. Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart

    DEFF Research Database (Denmark)

    Osadchii, Oleg E.

    2016-01-01

    examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. DESIGN: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon...... a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. RESULTS: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged...

  15. Dual Rate Adaptive Control for an Industrial Heat Supply Process Using Signal Compensation Approach

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Tianyou; Jia, Yao; Wang, Hong; Su, Chun-Yi

    2017-07-09

    The industrial heat supply process (HSP) is a highly nonlinear cascaded process which uses a steam valve opening as its control input, the steam flow-rate as its inner loop output and the supply water temperature as its outer loop output. The relationship between the heat exchange rate and the model parameters, such as steam density, entropy, and fouling correction factor and heat exchange efficiency are unknown and nonlinear. Moreover, these model parameters vary in line with steam pressure, ambient temperature and the residuals caused by the quality variations of the circulation water. When the steam pressure and the ambient temperature are of high values and are subjected to frequent external random disturbances, the supply water temperature and the steam flow-rate would interact with each other and fluctuate a lot. This is also true when the process exhibits unknown characteristic variations of the process dynamics caused by the unexpected changes of the heat exchange residuals. As a result, it is difficult to control the supply water temperature and the rates of changes of steam flow-rate well inside their targeted ranges. In this paper, a novel compensation signal based dual rate adaptive controller is developed by representing the unknown variations of dynamics as unmodeled dynamics. In the proposed controller design, such a compensation signal is constructed and added onto the control signal obtained from the linear deterministic model based feedback control design. Such a compensation signal aims at eliminating the unmodeled dynamics and the rate of changes of the currently sample unmodeled dynamics. A successful industrial application is carried out, where it has been shown that both the supply water temperature and the rate of the changes of the steam flow-rate can be controlled well inside their targeted ranges when the process is subjected to unknown variations of its dynamics.

  16. Albino mutation rates in red mangroves (Rhizophora mangle L.) as a bioassay of contamination history in Tampa Bay, Florida, USA

    Science.gov (United States)

    Proffitt, C.E.; Travis, S.E.

    2005-01-01

    We assessed the sensitivity of a viviparous estuarine tree species, Rhizophora mangle, to historic sublethal mutagenic stress across a fine spatial scale by comparing the frequency of trees producing albino propagules in historically contaminated (n=4) and uncontaminated (n=11) forests in Tampa Bay, Florida, USA. Data from uncontaminated forests were used to provide estimates of background mutation rates. We also determined whether other fitness parameters were negatively correlated with mutagenic stress (e.g., degree of outcrossing and numbers of reproducing trees km-1). Contaminated sites in Tampa Bay had significantly higher frequencies of trees that were heterozygous for albinism per 1000 total reproducing trees (FHT) than uncontaminated forests (mean ?? SE: 11.4 ?? 4.3 vs 4.3 ?? 0.73, P 25 yrs of subsequent recruitment and tree replacement may have allowed an initial elevation in the FHT to decay. Patterns of FHT were not explained by distance from the bay mouth or the degree of urbanization. However, there was a significant positive relationship between tree size and FHT (r=0.83, Pbioassay for the effects of mutagens will facilitate future monitoring of contamination events and comparisons of bay-wide recovery in future decades. Development of a database of FHT values for a range of subtropical and tropical estuaries is underway that will provide a baseline against which to compare mutational consequences of global change. ?? 2005, The Society of Wetland Scientists.

  17. Generation time, life history and the substitution rate of neutral mutations.

    Science.gov (United States)

    Lehtonen, Jussi; Lanfear, Robert

    2014-11-01

    Our understanding of molecular evolution is hampered by a lack of quantitative predictions about how life-history (LH) traits should correlate with substitution rates. Comparative studies have shown that neutral substitution rates vary substantially between species, and evidence shows that much of this diversity is associated with variation in LH traits. However, while these studies often agree, some unexplained and contradictory results have emerged. Explaining these results is difficult without a clear theoretical understanding of the problem. In this study, we derive predictions for the relationships between LH traits and substitution rates in iteroparous species by using demographic theory to relate commonly measured life-history traits to genetic generation time, and by implication to neutral substitution rates. This provides some surprisingly simple explanations for otherwise confusing patterns, such as the association between fecundity and substitution rates. The same framework can be applied to more complex life histories if full life-tables are available. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

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

    Science.gov (United States)

    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.

  19. HLW disposal by fission reactors; calculation of trans-mutation rate and recycle

    International Nuclear Information System (INIS)

    Mulyanto

    1997-01-01

    Transmutation of MA (Minor actinide) and LLFPS (long-lived fission products) into stable nuclide or short-lived isotopes by fission reactors seem to become an alternative technology for HLW disposal. in this study, transmutation rate and recycle calculation were developed in order to evaluate transmutation characteristics of MA and LLFPs in the fission reactors. inventory of MA and LLFPs in the transmutation reactors were determined by solving of criticality equation with 1-D cylindrical geometry of multigroup diffusion equations at the beginning of cycle (BOC). transmutation rate and burn-up was determined by solving of depletion equation. inventory of MA and LLFPs was calculated for 40 years recycle. From this study, it was concluded that characteristics of MA and LLFPs in the transmutation reactors can be evaluated by recycle calculation. by calculation of transmutation rate, performance of fission reactor for transmutation of MA or LLFPs can be discussed

  20. Different effects of dose rate on radiation-induced mutation frequency in various germ-cell stages of the mouse, and their implications for the analysis of tumorigenesis

    International Nuclear Information System (INIS)

    Russell, W.L.

    1979-01-01

    The following factors affecting mutation induction by radiation in mice are discussed: dose rate, cell stage, and sex. It is suggested that for cancers of presumed mutational origin, the risk from chronic radiation exposure may be only one-third the risk from acute exposure. This is based only on responses of spermatogonia; other cell types behave quite differently. Specific and general applications are discussed

  1. Performance of the JPEG Estimated Spectrum Adaptive Postfilter (JPEG-ESAP) for Low Bit Rates

    Science.gov (United States)

    Linares, Irving (Inventor)

    2016-01-01

    Frequency-based, pixel-adaptive filtering using the JPEG-ESAP algorithm for low bit rate JPEG formatted color images may allow for more compressed images while maintaining equivalent quality at a smaller file size or bitrate. For RGB, an image is decomposed into three color bands--red, green, and blue. The JPEG-ESAP algorithm is then applied to each band (e.g., once for red, once for green, and once for blue) and the output of each application of the algorithm is rebuilt as a single color image. The ESAP algorithm may be repeatedly applied to MPEG-2 video frames to reduce their bit rate by a factor of 2 or 3, while maintaining equivalent video quality, both perceptually, and objectively, as recorded in the computed PSNR values.

  2. Adaptive transmission based on multi-relay selection and rate-compatible LDPC codes

    Science.gov (United States)

    Su, Hualing; He, Yucheng; Zhou, Lin

    2017-08-01

    In order to adapt to the dynamical changeable channel condition and improve the transmissive reliability of the system, a cooperation system of rate-compatible low density parity check (RC-LDPC) codes combining with multi-relay selection protocol is proposed. In traditional relay selection protocol, only the channel state information (CSI) of source-relay and the CSI of relay-destination has been considered. The multi-relay selection protocol proposed by this paper takes the CSI between relays into extra account in order to obtain more chances of collabration. Additionally, the idea of hybrid automatic request retransmission (HARQ) and rate-compatible are introduced. Simulation results show that the transmissive reliability of the system can be significantly improved by the proposed protocol.

  3. Structural Breaks and Long Memory Property in Korean Won Exchange Rates: Adaptive FIGARCH Model

    Directory of Open Access Journals (Sweden)

    Young Wook Han

    2011-06-01

    Full Text Available This paper explores the issue of structural breaks and long memory property in the conditional variance process of the Korean exchange rates. To analyze the above in detail, this paper examines the dynamics of the structural breaks and the long memory in the conditional variance process of the Korean exchange returns by using the daily KRW-USD and KRW-JPY exchange rates for the period from 2000 through 2007. In particular, this paper employs the Adaptive FIGARCH model of Baillie and Morana (2009 which account for the structural breaks and the long memory property together. This paper also finds that the new Adaptive FIGARCH model outperforms the usual FIGARCH model of Baillie et al. (1996 when the structural breaks are present and that the long memory property in the conditional variance process of the Korean exchange returns is significantly reduced after the structural breaks are accounted for. Thus, these results suggest that the upward biased long memory property observed in the conditional variance process of the Korean exchange returns could partially have been imparted as a result of neglecting the structural breaks.

  4. Sensitivity of adaptive enrichment trial designs to accrual rates, time to outcome measurement, and prognostic variables

    Directory of Open Access Journals (Sweden)

    Tianchen Qian

    2017-12-01

    Full Text Available Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. Trial characteristics such as the accrual rate and the prognostic value of baseline variables are typically unknown when a trial is being planned; these values are typically assumed based on information available before the trial starts. Because of the added complexity in adaptive enrichment designs compared to standard designs, it may be of special concern how sensitive the trial performance is to deviations from assumptions. Through simulation studies, we evaluate the sensitivity of Type I error, power, expected sample size, and trial duration to different design characteristics. Our simulation distributions mimic features of data from the Alzheimer's Disease Neuroimaging Initiative cohort study, and involve two subpopulations based on a genetic marker. We investigate the impact of the following design characteristics: the accrual rate, the time from enrollment to measurement of a short-term outcome and the primary outcome, and the prognostic value of baseline variables and short-term outcomes. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator, and investigate its strengths and limitations compared to standard estimators. We apply information-based monitoring, and evaluate how accurately information can be estimated in an ongoing trial.

  5. Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China.

    Science.gov (United States)

    Li, Xiaodong; Liu, Yan; Xin, Shaojie; Ji, Dong; You, Shaoli; Hu, Jinhua; Zhao, Jun; Wu, Jingjing; Liao, Hao; Zhang, Xin-Xin; Xu, Dongping

    2017-06-01

    The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.

  6. Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

    Science.gov (United States)

    Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

    2017-01-05

    CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  8. 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.

  9. Compositional and mutational rate heterogeneity in mitochondrial genomes and its effect on the phylogenetic inferences of Cimicomorpha (Hemiptera: Heteroptera).

    Science.gov (United States)

    Yang, Huanhuan; Li, Teng; Dang, Kai; Bu, Wenjun

    2018-04-18

    Mitochondrial genome (mt-genome) data can potentially return artefactual relationships in the higher-level phylogenetic inference of insects due to the biases of accelerated substitution rates and compositional heterogeneity. Previous studies based on mt-genome data alone showed a paraphyly of Cimicomorpha (Insecta, Hemiptera) due to the positions of the families Tingidae and Reduviidae rather than the monophyly that was supported based on morphological characters, morphological and molecular combined data and large scale molecular datasets. Various strategies have been proposed to ameliorate the effects of potential mt-genome biases, including dense taxon sampling, removal of third codon positions or purine-pyrimidine coding and the use of site-heterogeneous models. In this study, we sequenced the mt-genomes of five additional Tingidae species and discussed the compositional and mutational rate heterogeneity in mt-genomes and its effect on the phylogenetic inferences of Cimicomorpha by implementing the bias-reduction strategies mentioned above. Heterogeneity in nucleotide composition and mutational biases were found in mt protein-coding genes, and the third codon exhibited high levels of saturation. Dense taxon sampling of Tingidae and Reduviidae and the other common strategies mentioned above were insufficient to recover the monophyly of the well-established group Cimicomorpha. When the sites with weak phylogenetic signals in the dataset were removed, the remaining dataset of mt-genomes can support the monophyly of Cimicomorpha; this support demonstrates that mt-genomes possess strong phylogenetic signals for the inference of higher-level phylogeny of this group. Comparison of the ratio of the removal of amino acids for each PCG showed that ATP8 has the highest ratio while CO1 has the lowest. This pattern is largely congruent with the evolutionary rate of 13 PCGs that ATP8 represents the highest evolutionary rate, whereas CO1 appears to be the lowest. Notably

  10. 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.

  11. Maximum Likelihood based comparison of the specific growth rates for P. aeruginosa and four mutator strains

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Mandsberg, Lotte Frigaard

    2008-01-01

    with an exponentially decaying function of the time between observations is suggested. A model with a full covariance structure containing OD-dependent variance and an autocorrelation structure is compared to a model with variance only and with no variance or correlation implemented. It is shown that the model...... are used for parameter estimation. The data is log-transformed such that a linear model can be applied. The transformation changes the variance structure, and hence an OD-dependent variance is implemented in the model. The autocorrelation in the data is demonstrated, and a correlation model...... that best describes data is a model taking into account the full covariance structure. An inference study is made in order to determine whether the growth rate of the five bacteria strains is the same. After applying a likelihood-ratio test to models with a full covariance structure, it is concluded...

  12. Heart rate variability indexes as a marker of chronic adaptation in athletes: a systematic review.

    Science.gov (United States)

    da Silva, Vanessa Pereira; de Oliveira, Natacha Alves; Silveira, Heitor; Mello, Roger Gomes Tavares; Deslandes, Andrea Camaz

    2015-03-01

    Regular exercise promotes functional and structural changes in the central and peripheral mechanisms of the cardiovascular system. Heart rate variability (HRV) measurement provides a sensitive indicator of the autonomic balance. However, because of the diversity of methods and variables used, the results are difficult to compare in the sports sciences. Since the protocol (supine, sitting, or standing position) and measure (time or frequency domain) are not well defined, the aim of this study is to investigate the HRV measures that better indicates the chronic adaptations of physical exercise in athletes. PubMed (MEDLINE), Web of Science, SciELO (Scientific Electronic Library), and Scopus databases were consulted. Original complete articles in English with short-term signals evaluating young and adult athletes, between 17 and 40 years old, with a control group, published up to 2013 were included. Selected 19 of 1369 studies, for a total sample pool of 333 male and female athletes who practice different sports. The main protocols observed were the supine or standing positions in free or controlled breathing conditions. The main statistical results found in this study were the higher mean RR, standard deviation of RR intervals, and high frequency in athletes group. In addition, the analyses of Cohen's effect size showed that factors as modality of sport, protocol used and unit of measure selected could influence this expected results. Our findings indicate that time domain measures are more consistent than frequency domain to describe the chronic cardiovascular autonomic adaptations in athletes. © 2014 Wiley Periodicals, Inc.

  13. Albino mutation rates in red mangroves (Rhizophora mangle L.) as a bioassay of contamination history in Tampa Bay, Florida, USA

    Science.gov (United States)

    Proffitt, C.E.; Travis, S.E.

    2005-01-01

    We assessed the sensitivity of a viviparous estuarine tree species, Rhizophora mangle, to historic sublethal mutagenic stress across a fine spatial scale by comparing the frequency of trees producing albino propagules in historically contaminated (n=4) and uncontaminated (n=11) forests in Tampa Bay, Florida, USA. Data from uncontaminated forests were used to provide estimates of background mutation rates. We also determined whether other fitness parameters were negatively correlated with mutagenic stress (e.g., degree of outcrossing and numbers of reproducing trees km-1). Contaminated sites in Tampa Bay had significantly higher frequencies of trees that were heterozygous for albinism per 1000 total reproducing trees (FHT) than uncontaminated forests (mean ?? SE: 11.4 ?? 4.3 vs 4.3 ?? 0.73, P 25 yrs of subsequent recruitment and tree replacement may have allowed an initial elevation in the FHT to decay. Patterns of FHT were not explained by distance from the bay mouth or the degree of urbanization. However, there was a significant positive relationship between tree size and FHT (r=0.83, P<0.018), which suggests that forests with older or larger trees provide a more lasting record of cumulative mutagenic stress. No other fitness parameters correlated with FHT. There was a difference in FHT between two latitudes, as determined by comparing Tampa Bay with literature values for Puerto Rico. The sensitivity of this bioassay for the effects of mutagens will facilitate future monitoring of contamination events and comparisons of bay-wide recovery in future decades. Development of a database of FHT values for a range of subtropical and tropical estuaries is underway that will provide a baseline against which to compare mutational consequences of global change. ?? 2005, The Society of Wetland Scientists.

  14. Adaptive Command Filtered Integrated Guidance and Control for Hypersonic Vehicle with Magnitude, Rate and Bandwidth Constraints

    Directory of Open Access Journals (Sweden)

    Wang Liang

    2018-01-01

    Full Text Available This paper proposes a novel integrated guidance and control (IGC method for hypersonic vehicle in terminal phase. Firstly, the system model is developed with a second order actuator dynamics. Then the back-stepping controller is designed hierarchically with command filters, where the first order command filters are implemented to construct the virtual control input with ideal states predicted by an adaptive estimator, and the nonlinear command filter is designed to produce magnitude, rate and bandwidth limited control surface deflection finally tracked by a terminal sliding mode controller with finite convergence time. Through a series of 6-DOF numerical simulations, it’s indicated that the proposed method successfully cancels out the large aerodynamics coefficient uncertainties and disturbances in hypersonic flight under limited control surface deflection. The contribution of this paper lies in the application and determination of nonlinear integrated design of guidance and control system for hypersonic vehicle.

  15. Adaptive changes in basal metabolic rate and thermogenesis in chronic undernutrition

    International Nuclear Information System (INIS)

    Shetty, P.S.

    1993-01-01

    Metabolic adaptation during chronic undernutrition represents a complex integration of several processes which affect the total energy expenditure of the individual. Basal metabolic rate (BMR) is reduced; reductions in BMR per unit fat free mass (FFM) is difficult to demonstrate. BMR changes in undernutrition reflect the low body weight as well as alterations in the composition of the FFM; more specifically changes in the ratio of viscera to muscle compartments of the FFM. Thermogenic responses to norepinephrine are transiently suppressed but recover rapidly on repeated stimulation. Dietary thermogenesis is enhanced possible the result of increases in tissue synthesis within the body. Changes in BMR and thermogenesis suggestive of an increase in metabolic efficiency is thus difficult to demonstrate in chronic undernutrition. (author). 15 refs, 2 figs, 7 tabs

  16. Adaptive Changes in Basal Metabolic Rate in Humans in Different Eco-Geographical Areas.

    Science.gov (United States)

    Maximov, Arkady L; Belkin, Victor Sh; Kalichman, Leonid; Kobyliansky, Eugene D

    2015-12-01

    Our aim was to establish whether the human basal metabolic rate (BMR) shifts towards the reduction of vital functions as an adaptation response to extreme environmental conditions. Data was collected in arid and Extreme North zones. The arid zone samples included Bedouins living in the Sinai Peninsula in Egypt, Turkmen students, the Pedagogical University of Chardzhou, Turkmenistan born Russians and Russian soldiers. Soldiers were divided into 3 groups according to the length of their tour of duty in the area: 1st group: up to six months, 2nd group: up to 2 years and the 3rd group: 3-5 years. The Extreme North samples comprised Chukchi natives, 1st generation Russian immigrants born in the area and 3 groups of soldiers comparable to the soldiers from Turkmenistan. BMR values of the new recruits had the highest values of total and relative BMR (1769 ± 16 and 28.3 ± 0.6, correspondingly). The total and relative BMR tended to decrease within a longer adaptation period. The BMR values of officers who served >3 years in Turkmenistan were very similar to the Turkmenistan born Russians (1730 ± 14 vs. 1726 ± 18 and 26.5 ± 0.6 vs. 27.3 ± 0.7, correspondingly). Similarly, in Chukotka, the highest relative BMR was found in the new recruits, serving up to 6 months (28.1 ± 0.7) and was significantly (p BMR was virtually similar in Russian officers serving > 3 years, compared to the middle-aged Chukchi or Chukotka-born Russians (25.8 ± 0.5 vs. 25.6 ± 0.5 and 25.5 ± 0.6, correspondingly). The BMR parameters demonstrated a stronger association with body weight than with age. In extreme environmental conditions, migrant populations showed a decrease in BMR, thus reducing its vital functions. The BMR reduction effect with the adequate adaptive transformation is likely to be the key strategy for developing programs to facilitate human and animal adaptation to extreme factors. This process is aimed at preserving the optimum energy balance and homeostasis while minimizing

  17. Multi-objective differential evolution with adaptive Cauchy mutation for short-term multi-objective optimal hydro-thermal scheduling

    Energy Technology Data Exchange (ETDEWEB)

    Qin Hui [College of Hydropower and Information Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Zhou Jianzhong, E-mail: jz.zhou@hust.edu.c [College of Hydropower and Information Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Lu Youlin; Wang Ying; Zhang Yongchuan [College of Hydropower and Information Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2010-04-15

    A new multi-objective optimization method based on differential evolution with adaptive Cauchy mutation (MODE-ACM) is presented to solve short-term multi-objective optimal hydro-thermal scheduling (MOOHS) problem. Besides fuel cost, the pollutant gas emission is also optimized as an objective. The water transport delay between connected reservoirs and the effect of valve-point loading of thermal units are also taken into account in the presented problem formulation. The proposed algorithm adopts an elitist archive to retain non-dominated solutions obtained during the evolutionary process. It modifies the DE's operators to make it suit for multi-objective optimization (MOO) problems and improve its performance. Furthermore, to avoid premature convergence, an adaptive Cauchy mutation is proposed to preserve the diversity of population. An effective constraints handling method is utilized to handle the complex equality and inequality constraints. The effectiveness of the proposed algorithm is tested on a hydro-thermal system consisting of four cascaded hydro plants and three thermal units. The results obtained by MODE-ACM are compared with several previous studies. It is found that the results obtained by MODE-ACM are superior in terms of fuel cost as well as emission output, consuming a shorter time. Thus it can be a viable alternative to generate optimal trade-offs for short-term MOOHS problem.

  18. Estimation of mutation rates induced by large doses of gamma, proton and neutron irradiation of the X-chromosome of the nematode Panagrellus redivivus

    International Nuclear Information System (INIS)

    Denich, K.T.R.; Samoiloff, M.R.

    1984-01-01

    The radiation-resistant free-living nematode Panagrellus redivivus was used to study mutation rates in oocytes, following gamma, proton and neutron irradiation in the dose range 45-225 grays. γ-Radiation produced approximately 0.001 lethal X-chromosomes per gray over the range tested. Proton or neutron irradiation produced approximately 0.003 lethal X-chromosomes per gray at lower doses, with the mutation rate dropping to 0.001 lethal X-chromosome per gray at the higher doses. These results suggest a dose-dependent mutation-repair system. Cell lethality was also examined. γ-Radiation produced the greatest amount of cell lethality at all doses, while neutron irradiation had no cell lethal effect at any of the doses examined. (orig.)

  19. Adaptive rate transmission for spectrum sharing system with quantized channel state information

    KAUST Repository

    Abdallah, Mohamed M.

    2011-03-01

    The capacity of a secondary link in spectrum sharing systems has been recently investigated in fading environments. In particular, the secondary transmitter is allowed to adapt its power and rate to maximize its capacity subject to the constraint of maximum interference level allowed at the primary receiver. In most of the literature, it was assumed that estimates of the channel state information (CSI) of the secondary link and the interference level are made available at the secondary transmitter via an infinite-resolution feedback links between the secondary/primary receivers and the secondary transmitter. However, the assumption of having infinite resolution feedback links is not always practical as it requires an excessive amount of bandwidth. In this paper we develop a framework for optimizing the performance of the secondary link in terms of the average spectral efficiency assuming quantized CSI available at the secondary transmitter. We develop a computationally efficient algorithm for optimally quantizing the CSI and finding the optimal power and rate employed at the cognitive transmitter for each quantized CSI level so as to maximize the average spectral efficiency. Our results give the number of bits required to represent the CSI sufficient to achieve almost the maximum average spectral efficiency attained using full knowledge of the CSI for Rayleigh fading channels. © 2011 IEEE.

  20. Adaptive rate transmission for spectrum sharing system with quantized channel state information

    KAUST Repository

    Abdallah, Mohamed M.; Salem, Ahmed H.; Alouini, Mohamed-Slim; Qaraqe, Khalid A.

    2011-01-01

    The capacity of a secondary link in spectrum sharing systems has been recently investigated in fading environments. In particular, the secondary transmitter is allowed to adapt its power and rate to maximize its capacity subject to the constraint of maximum interference level allowed at the primary receiver. In most of the literature, it was assumed that estimates of the channel state information (CSI) of the secondary link and the interference level are made available at the secondary transmitter via an infinite-resolution feedback links between the secondary/primary receivers and the secondary transmitter. However, the assumption of having infinite resolution feedback links is not always practical as it requires an excessive amount of bandwidth. In this paper we develop a framework for optimizing the performance of the secondary link in terms of the average spectral efficiency assuming quantized CSI available at the secondary transmitter. We develop a computationally efficient algorithm for optimally quantizing the CSI and finding the optimal power and rate employed at the cognitive transmitter for each quantized CSI level so as to maximize the average spectral efficiency. Our results give the number of bits required to represent the CSI sufficient to achieve almost the maximum average spectral efficiency attained using full knowledge of the CSI for Rayleigh fading channels. © 2011 IEEE.

  1. Interest Level in 2-Year-Olds with Autism Spectrum Disorder Predicts Rate of Verbal, Nonverbal, and Adaptive Skill Acquisition

    Science.gov (United States)

    Klintwall, Lars; Macari, Suzanne; Eikeseth, Svein; Chawarska, Katarzyna

    2015-01-01

    Recent studies have suggested that skill acquisition rates for children with autism spectrum disorders receiving early interventions can be predicted by child motivation. We examined whether level of interest during an Autism Diagnostic Observation Schedule assessment at 2?years predicts subsequent rates of verbal, nonverbal, and adaptive skill…

  2. Adaptive Rates of High-Spectral-Efficiency WDM/SDM Channels Using PDM-1024-QAM Probabilistic Shaping

    DEFF Research Database (Denmark)

    Hu, Hao; Yankov, Metodi Plamenov; Da Ros, Francesco

    2017-01-01

    We demonstrate adaptive rates and spectral efficiencies in WDM/SDM transmission using probabilistically shaped PDM-1024-QAM signals, achieving up to 7-Tbit/s data rates per spatial-superchannel and up to 297.8-bit/s/Hz aggregate spectral efficiency using a 30-core fiber on 12.5 and 25GHz WDM grids...

  3. The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

    OpenAIRE

    Heath, Kathleen M.; Axton, Jacob H.; McCullough, John M.; Harris, Nathan

    2016-01-01

    ABSTRACT Objectives The C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronut...

  4. On the Performance of Adaptive Data Rate over Deep Space Ka-Bank Link: Case Study Using Kepler Data

    Science.gov (United States)

    Gao, Jay L.

    2016-01-01

    Future missions envisioned for both human and robotic exploration demand increasing communication capacity through the use of Ka-band communications. The Ka-band channel, being more sensitive to weather impairments, presents a unique trade-offs between data storage, latency, data volume and reliability. While there are many possible techniques for optimizing Ka-band operations such as adaptive modulation and coding and site-diversity, this study focus exclusively on the use of adaptive data rate (ADR) to achieve significant improvement in the data volume-availability tradeoff over a wide range of link distances for near Earth and Mars exploration. Four years of Kepler Ka-band downlink symbol signal-to-noise (SNR) data reported by the Deep Space Network were utilized to characterize the Ka-band channel statistics at each site and conduct various what-if performance analysis for different link distances. We model a notional closed-loop adaptive data rate system in which an algorithm predicts the channel condition two-way light time (TWLT) into the future using symbol SNR reported in near-real time by the ground receiver and determines the best data rate to use. Fixed and adaptive margins were used to mitigate errors in channel prediction. The performance of this closed-loop adaptive data rate approach is quantified in terms of data volume and availability and compared to the actual mission configuration and a hypothetical, optimized single rate configuration assuming full a priori channel knowledge.

  5. What You See is what You Just Heard: The Effect of Temporal Rate Adaptation on Human Intersensory Perception

    Directory of Open Access Journals (Sweden)

    Carmel Levitan

    2011-10-01

    Full Text Available Previous studies on perception have yet to establish that psychophysical adaptation effects transfer from one sense to another. To test for this phenomenon, the current study examines the possible crossmodal transfer of temporal rate adaptation from vision to audition (VA and from audition to vision (AV. Participants were trained, using feedback, to discriminate the perceived rapidity of either auditory or visual stimuli presented at a range of randomly-ordered frequencies (3.25–4.75 Hz as compared to that of stimuli (of the same modality at a familiar average frequency (4 Hz. Afterwards, subjects were repeatedly exposed to stimuli (of the other modality at a specific rate (3 Hz or 5 Hz. To test whether adaptation resulted from this exposure, subjects again completed the task previously used for training, but now without feedback. After the initial training and adaptation phases, these test and adaptation tasks were presented in 20 alternating blocks. A comparison of the pre- and post-adaptation responses showed crossmodal changes in subjects' perception of temporal rate, such that adaptation to 5 Hz led to the subsequent stimuli seeming slower than they had before adaptation. On the other hand, after exposure to 3 Hz stimuli, the opposite effect was seen. This shift occurred in both VA and AV conditions. As audition and vision were never simultaneously presented, this is suggestive of a strong linkage between the two modalities in perceiving rate. We propose that this is due to the presence of early, distributed, within-modal clocks, that can vigorously modulate each other cross-modally.

  6. Disparity mutagenesis model possesses the ability to realize both stable and rapid evolution in response to changing environments without altering mutation rates.

    Directory of Open Access Journals (Sweden)

    Ichiro Fujihara

    2016-08-01

    As long as the fidelity difference between the lagging and leading strand was kept high enough, the robustness of the disparity model was very high. The acceleration or slowdown of evolution can be unambiguously introduced only by environmental changes, and the seesawing mutation rate is not the necessary condition for changing the speed of evolution.

  7. Efficient inference of population size histories and locus-specific mutation rates from large-sample genomic variation data.

    Science.gov (United States)

    Bhaskar, Anand; Wang, Y X Rachel; Song, Yun S

    2015-02-01

    With the recent increase in study sample sizes in human genetics, there has been growing interest in inferring historical population demography from genomic variation data. Here, we present an efficient inference method that can scale up to very large samples, with tens or hundreds of thousands of individuals. Specifically, by utilizing analytic results on the expected frequency spectrum under the coalescent and by leveraging the technique of automatic differentiation, which allows us to compute gradients exactly, we develop a very efficient algorithm to infer piecewise-exponential models of the historical effective population size from the distribution of sample allele frequencies. Our method is orders of magnitude faster than previous demographic inference methods based on the frequency spectrum. In addition to inferring demography, our method can also accurately estimate locus-specific mutation rates. We perform extensive validation of our method on simulated data and show that it can accurately infer multiple recent epochs of rapid exponential growth, a signal that is difficult to pick up with small sample sizes. Lastly, we use our method to analyze data from recent sequencing studies, including a large-sample exome-sequencing data set of tens of thousands of individuals assayed at a few hundred genic regions. © 2015 Bhaskar et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

    Science.gov (United States)

    Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

    2015-09-04

    Usher syndrome (USH) is the most common disease causing combined deafness and blindness. It is predominantly an autosomal recessive genetic disorder with occasionally digenic cases. Molecular diagnosis of USH patients is important for disease management. Few studies have tried to find the genetic cause of USH in Chinese patients. This study was designed to determine the mutation spectrum of Chinese USH patients. We applied next generation sequencing to characterize the mutation spectrum in 67 independent Chinese families with at least one member diagnosed with USH. Blood was collected at Peking Union Medical College Hospital. This cohort is one of the largest USH cohorts reported. We utilized customized panel and whole exome sequencing, variant analysis, Sanger validation and segregation tests to find disease causing mutations in these families. We identified biallelic disease causing mutations in known USH genes in 70 % (49) of our patients. As has been previously reported, MYO7A is the most frequently mutated gene in our USH type I patients while USH2A is the most mutated gene in our USH type II patients. In addition, we identify mutations in CLRN1, DFNB31, GPR98 and PCDH15 for the first time in Chinese USH patients. Together, mutations in CLRN1, DNFB31, GPR98 and PCDH15 account for 11.4 % of disease in our cohort. Interestingly, although the spectrum of disease genes is quite similar between our Chinese patient cohort and other patient cohorts from different (and primarily Caucasian) ethnic backgrounds, the mutations themselves are dramatically different. In particular, 76 % (52/68) of alleles found in this study have never been previously reported. Interestingly, we observed a strong enrichment for severe protein truncating mutations expected to have severe functional consequence on the protein in USH II patients compared to the reported mutation spectrum in RP patients, who often carry partial protein truncating mutations. Our study provides the first

  9. Vacuolar Protein Sorting Genes in Parkinson's Disease: A Re-appraisal of Mutations Detection Rate and Neurobiology of Disease.

    Science.gov (United States)

    Gambardella, Stefano; Biagioni, Francesca; Ferese, Rosangela; Busceti, Carla L; Frati, Alessandro; Novelli, Giuseppe; Ruggieri, Stefano; Fornai, Francesco

    2016-01-01

    Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN). Recently, retromer alterations have been related to the onset of Parkinson's Disease (PD) since the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35) was identified as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation. Other mutations in VPS genes have been reported in both sporadic and familial PD. These mutations are less defined. Understanding the specific prevalence of all VPS gene mutations is key to understand the relevance of retromers impairment in the onset of PD. A number of PD-related mutations despite affecting different biochemical systems (autophagy, mitophagy, proteasome, endosomes, protein folding), all converge in producing an impairment in cell clearance. This may explain how genetic predispositions to PD may derive from slightly deleterious VPS mutations when combined with environmental agents overwhelming the clearance of the cell. This manuscript reviews genetic data produced in the last 5 years to re-define the actual prevalence of VPS gene mutations in the onset of PD. The prevalence of p.Asp620Asn mutation in VPS35 is 0.286 of familial PD. This increases up to 0.548 when considering mutations affecting all VPS genes. This configures mutations in VPS genes as the second most frequent autosomal dominant PD genotype. This high prevalence, joined with increased awareness of the role played by retromers in the neurobiology of PD, suggests environmentally-induced VPS alterations as crucial in the genesis of PD.

  10. Vacuolar Protein Sorting Genes in Parkinson's Disease: A Re-appraisal of Mutations Detection Rate and Neurobiology of Disease

    Science.gov (United States)

    Gambardella, Stefano; Biagioni, Francesca; Ferese, Rosangela; Busceti, Carla L.; Frati, Alessandro; Novelli, Giuseppe; Ruggieri, Stefano; Fornai, Francesco

    2016-01-01

    Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN). Recently, retromer alterations have been related to the onset of Parkinson's Disease (PD) since the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35) was identified as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation. Other mutations in VPS genes have been reported in both sporadic and familial PD. These mutations are less defined. Understanding the specific prevalence of all VPS gene mutations is key to understand the relevance of retromers impairment in the onset of PD. A number of PD-related mutations despite affecting different biochemical systems (autophagy, mitophagy, proteasome, endosomes, protein folding), all converge in producing an impairment in cell clearance. This may explain how genetic predispositions to PD may derive from slightly deleterious VPS mutations when combined with environmental agents overwhelming the clearance of the cell. This manuscript reviews genetic data produced in the last 5 years to re-define the actual prevalence of VPS gene mutations in the onset of PD. The prevalence of p.Asp620Asn mutation in VPS35 is 0.286 of familial PD. This increases up to 0.548 when considering mutations affecting all VPS genes. This configures mutations in VPS genes as the second most frequent autosomal dominant PD genotype. This high prevalence, joined with increased awareness of the role played by retromers in the neurobiology of PD, suggests environmentally-induced VPS alterations as crucial in the genesis of PD. PMID:27932943

  11. The influence of continuous γ-irradiation at decreasing dose-rate on the survival rote and induction of gene mutations in cultured Chinese hamster cells

    International Nuclear Information System (INIS)

    Feoktistova, T.P.; Elisova, E.V.; Stavrakova, N.M.

    1991-01-01

    Continuous γ-irradiation at decreasing dose-rate was shown to be less effective than acute exposure with regard to the lethal effect and frequency of mutations of resistance to 6-thioguanine in cultured Chinese hamster cells. The cell population subjected to continuons irradiation was d more radioresistant than the intact one. Lethal and genetic effects of continuous irradiation at decreasing dose-rate were mainly determined by the contribution of the radiation dose received during the first 24 h of exposure

  12. Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions

    Science.gov (United States)

    In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained several positively charged amino acids...

  13. CONSTRUCTION AND ADAPTATION OF GENETIC SEXING STRAIN OF THE MEDFLY CERATITIS CAPITATA (WIED.)BASED ON TEMPERATURE SENSITIVE MUTATION IN THE EGYPTIAN FRUITFLY LABORATORIES

    International Nuclear Information System (INIS)

    SHOMAN, A.A.

    2007-01-01

    Special strains that produce only males are used now for the control of the medfly Ceratitis capitata using the sterile insect technique. The use of these strains has a major impact on the overall efficiency of SIT, by increasing significantly the amount of sterility induced in field population comparing by using bisexual strains. Genetic sexing strains (GSS) are based on the use of male-linked chromosomal translocations which enable selectable marker genes to be linked to the male sex. Two basic components are required in the medfly to construct and adapt a laboratory strain which exhibits genetic sexing properties. The first is Y-auto some translocation strain, which enables male and female pupae to be differentiated on the basis of colour and the second is temperature sensitive lethal (tsl) mutation strain, which enables females to be killed by an increase in ambient temperature

  14. Weakly Deleterious Mutations and Low Rates of Recombination Limit the Impact of Natural Selection on Bacterial Genomes.

    Science.gov (United States)

    Price, Morgan N; Arkin, Adam P

    2015-12-15

    Free-living bacteria are usually thought to have large effective population sizes, and so tiny selective differences can drive their evolution. However, because recombination is infrequent, "background selection" against slightly deleterious alleles should reduce the effective population size (Ne) by orders of magnitude. For example, for a well-mixed population with 10(12) individuals and a typical level of homologous recombination (r/m = 3, i.e., nucleotide changes due to recombination [r] occur at 3 times the mutation rate [m]), we predict that Ne is selection should be sufficient to drive evolution if Ne × s is >1, where s is the selection coefficient. We found that this remains approximately correct if background selection is occurring or when population structure is present. Overall, we predict that even for free-living bacteria with enormous populations, natural selection is only a significant force if s is above 10(-7) or so. Because bacteria form huge populations with trillions of individuals, the simplest theoretical prediction is that the better allele at a site would predominate even if its advantage was just 10(-9) per generation. In other words, virtually every nucleotide would be at the local optimum in most individuals. A more sophisticated theory considers that bacterial genomes have millions of sites each and selection events on these many sites could interfere with each other, so that only larger effects would be important. However, bacteria can exchange genetic material, and in principle, this exchange could eliminate the interference between the evolution of the sites. We used simulations to confirm that during multisite evolution with realistic levels of recombination, only larger effects are important. We propose that advantages of less than 10(-7) are effectively neutral. Copyright © 2015 Price and Arkin.

  15. Transmission History Based Distributed Adaptive Contention Window Adjustment Algorithm Cooperating with Automatic Rate Fallback for Wireless LANs

    Science.gov (United States)

    Ogawa, Masakatsu; Hiraguri, Takefumi; Nishimori, Kentaro; Takaya, Kazuhiro; Murakawa, Kazuo

    This paper proposes and investigates a distributed adaptive contention window adjustment algorithm based on the transmission history for wireless LANs called the transmission-history-based distributed adaptive contention window adjustment (THAW) algorithm. The objective of this paper is to reduce the transmission delay and improve the channel throughput compared to conventional algorithms. The feature of THAW is that it adaptively adjusts the initial contention window (CWinit) size in the binary exponential backoff (BEB) algorithm used in the IEEE 802.11 standard according to the transmission history and the automatic rate fallback (ARF) algorithm, which is the most basic algorithm in automatic rate controls. This effect is to keep CWinit at a high value in a congested state. Simulation results show that the THAW algorithm outperforms the conventional algorithms in terms of the channel throughput and delay, even if the timer in the ARF is changed.

  16. Adaptive high learning rate probabilistic disruption predictors from scratch for the next generation of tokamaks

    International Nuclear Information System (INIS)

    Vega, J.; Moreno, R.; Pereira, A.; Acero, A.; Murari, A.; Dormido-Canto, S.

    2014-01-01

    The development of accurate real-time disruption predictors is a pre-requisite to any mitigation action. Present theoretical models of disruptions do not reliably cope with the disruption issues. This article deals with data-driven predictors and a review of existing machine learning techniques, from both physics and engineering points of view, is provided. All these methods need large training datasets to develop successful predictors. However, ITER or DEMO cannot wait for hundreds of disruptions to have a reliable predictor. So far, the attempts to extrapolate predictors between different tokamaks have not shown satisfactory results. In addition, it is not clear how valid this approach can be between present devices and ITER/DEMO, due to the differences in their respective scales and possibly underlying physics. Therefore, this article analyses the requirements to create adaptive predictors from scratch to learn from the data of an individual machine from the beginning of operation. A particular algorithm based on probabilistic classifiers has been developed and it has been applied to the database of the three first ITER-like wall campaigns of JET (1036 non-disruptive and 201 disruptive discharges). The predictions start from the first disruption and only 12 re-trainings have been necessary as a consequence of missing 12 disruptions only. Almost 10 000 different predictors have been developed (they differ in their features) and after the chronological analysis of the 1237 discharges, the predictors recognize 94% of all disruptions with an average warning time (AWT) of 654 ms. This percentage corresponds to the sum of tardy detections (11%), valid alarms (76%) and premature alarms (7%). The false alarm rate is 4%. If only valid alarms are considered, the AWT is 244 ms and the standard deviation is 205 ms. The average probability interval about the reliability and accuracy of all the individual predictions is 0.811 ± 0.189. (paper)

  17. Adaptive high learning rate probabilistic disruption predictors from scratch for the next generation of tokamaks

    Science.gov (United States)

    Vega, J.; Murari, A.; Dormido-Canto, S.; Moreno, R.; Pereira, A.; Acero, A.; Contributors, JET-EFDA

    2014-12-01

    The development of accurate real-time disruption predictors is a pre-requisite to any mitigation action. Present theoretical models of disruptions do not reliably cope with the disruption issues. This article deals with data-driven predictors and a review of existing machine learning techniques, from both physics and engineering points of view, is provided. All these methods need large training datasets to develop successful predictors. However, ITER or DEMO cannot wait for hundreds of disruptions to have a reliable predictor. So far, the attempts to extrapolate predictors between different tokamaks have not shown satisfactory results. In addition, it is not clear how valid this approach can be between present devices and ITER/DEMO, due to the differences in their respective scales and possibly underlying physics. Therefore, this article analyses the requirements to create adaptive predictors from scratch to learn from the data of an individual machine from the beginning of operation. A particular algorithm based on probabilistic classifiers has been developed and it has been applied to the database of the three first ITER-like wall campaigns of JET (1036 non-disruptive and 201 disruptive discharges). The predictions start from the first disruption and only 12 re-trainings have been necessary as a consequence of missing 12 disruptions only. Almost 10 000 different predictors have been developed (they differ in their features) and after the chronological analysis of the 1237 discharges, the predictors recognize 94% of all disruptions with an average warning time (AWT) of 654 ms. This percentage corresponds to the sum of tardy detections (11%), valid alarms (76%) and premature alarms (7%). The false alarm rate is 4%. If only valid alarms are considered, the AWT is 244 ms and the standard deviation is 205 ms. The average probability interval about the reliability and accuracy of all the individual predictions is 0.811 ± 0.189.

  18. ITER FW cooling by a flat channel, adapted to low flow rate and high pressure drop

    International Nuclear Information System (INIS)

    Ovchinnikov, I.B.; Bondarchuk, D.E.; Gervash, A.A.; Glazunov, D.A.; Komarov, A.O.; Kuznetsov, V.E.; Mazul, I.V.; Rulev, R.V.; Yablokov, N.A.

    2011-01-01

    Highlights: ► ITER FW cooling: pressure drop quotation must be assigned according to thermal load. ► Flat channel solutions with wide range (1:500) of hydraulic resistivity are presented. ► Simulations in Ansys CFX were carried out for presented designs. ► Usage of pressure drop quotation significantly reduces surface temperature. ► Experiments in TSEFEY-M facility confirm simulations. - Abstract: Application of hypervapotron (HV) to cool in-vessel components of ITER – divertor and first wall (FW) – is characterized by the same design load (5 MW/m 2 ) but water flow rate for FW is 8–9 times (almost by order!) less for parallel feeding elements so it seems it would be better to use other design. Several variants of a flat channel design different from HV are suggested that enable to adapt a channel to pressure quota up to 1 MPa and higher. A main feature of the suggested variants is a spiral or multi-spiral stream (flat multi spiral––FMS) that improves heat rejection and can be obtained both by exciting of such mode and forced by channel geometry. Comparison of the variants was carried out in simulations (Ansys CFX) as well as in experiments on the TSEFEY-M facility with electron-beam gun. It is shown that excitation of a spiral stream in a channel significantly reduces a temperature of a loaded surface of a channel. Miniature thermocouples were used to measure temperature near the surface.

  19. The Parent Version of the Preschool Social Skills Rating System: Psychometric Analysis and Adaptation with a German Preschool Sample

    Science.gov (United States)

    Hess, Markus; Scheithauer, Herbert; Kleiber, Dieter; Wille, Nora; Erhart, Michael; Ravens-Sieberer, Ulrike

    2014-01-01

    The Social Skills Rating System (SSRS) developed by Gresham and Elliott (1990) is a multirater, norm-referenced instrument measuring social skills and adaptive behavior in preschool children. The aims of the present study were (a) to test the factorial structure of the Parent Form of the SSRS for the first time with a German preschool sample (391…

  20. Interest level in 2-year-olds with autism spectrum disorder predicts rate of verbal, nonverbal, and adaptive skill acquisition

    OpenAIRE

    Klintwall, Lars; Macari, Suzanne; Eikeseth, Svein; Chawarska, Katarzyna

    2014-01-01

    Recent studies have suggested that skill acquisition rates for children with autism spectrum disorders receiving early interventions can be predicted by child motivation. We examined whether level of interest during an Autism Diagnostic Observation Schedule assessment at 2 years predicts subsequent rates of verbal, nonverbal, and adaptive skill acquisition to the age of 3 years. A total of 70 toddlers with autism spectrum disorder, mean age of 21.9 months, were scored using Interest Level Sco...

  1. Adaptation of the chlorophycean Dictyosphaerium chlorelloides to stressful acidic, mine metal-rich waters as result of pre-selective mutations.

    Science.gov (United States)

    López-Rodas, Victoria; Marvá, Fernando; Rouco, Mónica; Costas, Eduardo; Flores-Moya, Antonio

    2008-06-01

    Several species of microalgae, closely related to mesophilic lineages, inhabit the extreme environment (pH 2.5, high levels of metals) of the Spain's Aguas Agrias Stream water (AASW). Consequently, AASW constitutes an interesting natural laboratory for analysis of adaptation by microalgae to extremely stressful conditions. To distinguish between the pre-selective or post-selective origin of adaptation processes allowing the existence of microalgae in AASW, a Luria-Delbrück fluctuation analysis was performed with the chlorophycean Dictyosphaerium chlorelloides isolated from non-acidic waters. In the analysis, AASW was used as selective factor. Preselective, resistant D. chlorelloides cells appeared with a frequency of 1.1 x 10(-6) per cell per generation. AASW-resistant mutants, with a diminished Malthusian fitness, are maintained in non-extreme waters as the result of a balance between new AASW-resistant cells arising by mutation and AASW-resistant mutants eliminated by natural selection (equilibrium at c. 12 AASW-resistants per 10(7) wild-type cells). We propose that the microalgae inhabiting this stressful environment could be the descendents of chance mutants that arrived in the past or are even arriving at the present.

  2. Active site mutations in yeast protein disulfide isomerase cause dithiothreitol sensitivity and a reduced rate of protein folding in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Holst, B; Tachibana, C; Winther, Jakob R.

    1997-01-01

    Aspects of protein disulfide isomerase (PDI) function have been studied in yeast in vivo. PDI contains two thioredoxin-like domains, a and a', each of which contains an active-site CXXC motif. The relative importance of the two domains was analyzed by rendering each one inactive by mutation to SGAS....... Such mutations had no significant effect on growth. The domains however, were not equivalent since the rate of folding of carboxypeptidase Y (CPY) in vivo was reduced by inactivation of the a domain but not the a' domain. To investigate the relevance of PDI redox potential, the G and H positions of each CGHC......-deleted strains overexpressing the yeast PDI homologue EUG1 are viable. Exchanging the wild-type Eug1p C(L/I)HS active site sequences for C(L/I)HC increased the growth rate significantly, however, further highlighting the importance of the oxidizing function for optimal growth....

  3. Optimizing the data acquisition rate for a remotely controllable structural monitoring system with parallel operation and self-adaptive sampling

    International Nuclear Information System (INIS)

    Sheng, Wenjuan; Guo, Aihuang; Liu, Yang; Azmi, Asrul Izam; Peng, Gang-Ding

    2011-01-01

    We present a novel technique that optimizes the real-time remote monitoring and control of dispersed civil infrastructures. The monitoring system is based on fiber Bragg gating (FBG) sensors, and transfers data via Ethernet. This technique combines parallel operation and self-adaptive sampling to increase the data acquisition rate in remote controllable structural monitoring systems. The compact parallel operation mode is highly efficient at achieving the highest possible data acquisition rate for the FBG sensor based local data acquisition system. Self-adaptive sampling is introduced to continuously coordinate local acquisition and remote control for data acquisition rate optimization. Key issues which impact the operation of the whole system, such as the real-time data acquisition rate, data processing capability, and buffer usage, are investigated. The results show that, by introducing parallel operation and self-adaptive sampling, the data acquisition rate can be increased by several times without affecting the system operating performance on both local data acquisition and remote process control

  4. 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.

  5. Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells

    NARCIS (Netherlands)

    Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.

    2001-01-01

    Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by

  6. Familial isolated primary hyperparathyroidism associated with germline GCM2 mutations is more aggressive and has a lesser rate of biochemical cure.

    Science.gov (United States)

    El Lakis, Mustapha; Nockel, Pavel; Guan, Bin; Agarwal, Sunita; Welch, James; Simonds, William F; Marx, Stephen; Li, Yulong; Nilubol, Naris; Patel, Dhaval; Yang, Lily; Merkel, Roxanne; Kebebew, Electron

    2018-01-01

    Hereditary primary hyperparathyroidism may be syndromic or nonsyndromic (familial isolated hyperparathyroidism). Recently, germline activating mutations in the GCM2 gene were identified in a subset of familial isolated hyperparathyroidism. This study examined the clinical and biochemical characteristics and the treatment outcomes of GCM2 mutation-positive familial isolated hyperparathyroidism as compared to sporadic primary hyperparathyroidism. We performed a retrospective analysis of clinical features, parathyroid pathology, and operative outcomes in 18 patients with GCM2 germline mutations and 457 patients with sporadic primary hyperparathyroidism. Age at diagnosis, sex distribution, race/ethnicity, and preoperative serum calcium concentrations were similar between the 2 groups. The preoperative serum levels of intact parathyroid hormone was greater in patients with GCM2-associated primary hyperparathyroidism (239 ± 394 vs 136 ± 113, P = .005) as were rates of multigland disease and parathyroid carcinoma in the GCM2 group (78% vs 14.3%, P hyperparathyroidism patients have greater preoperative parathyroid hormone levels, a greater rate of multigland disease, a lesser rate of biochemical cure, and a substantial risk of parathyroid carcinoma. Knowledge of these clinical characteristics could optimize the surgical management of GCM2-associated familial isolated hyperparathyroidism. Published by Elsevier Inc.

  7. Unequal Protection of Video Streaming through Adaptive Modulation with a Trizone Buffer over Bluetooth Enhanced Data Rate

    Directory of Open Access Journals (Sweden)

    Razavi Rouzbeh

    2008-01-01

    Full Text Available Abstract Bluetooth enhanced data rate wireless channel can support higher-quality video streams compared to previous versions of Bluetooth. Packet loss when transmitting compressed data has an effect on the delivered video quality that endures over multiple frames. To reduce the impact of radio frequency noise and interference, this paper proposes adaptive modulation based on content type at the video frame level and content importance at the macroblock level. Because the bit rate of protected data is reduced, the paper proposes buffer management to reduce the risk of buffer overflow. A trizone buffer is introduced, with a varying unequal protection policy in each zone. Application of this policy together with adaptive modulation results in up to 4 dB improvement in objective video quality compared to fixed rate scheme for an additive white Gaussian noise channel and around 10 dB for a Gilbert-Elliott channel. The paper also reports a consistent improvement in video quality over a scheme that adapts to channel conditions by varying the data rate without accounting for the video frame packet type or buffer congestion.

  8. Unequal Protection of Video Streaming through Adaptive Modulation with a Trizone Buffer over Bluetooth Enhanced Data Rate

    Directory of Open Access Journals (Sweden)

    Rouzbeh Razavi

    2007-12-01

    Full Text Available Bluetooth enhanced data rate wireless channel can support higher-quality video streams compared to previous versions of Bluetooth. Packet loss when transmitting compressed data has an effect on the delivered video quality that endures over multiple frames. To reduce the impact of radio frequency noise and interference, this paper proposes adaptive modulation based on content type at the video frame level and content importance at the macroblock level. Because the bit rate of protected data is reduced, the paper proposes buffer management to reduce the risk of buffer overflow. A trizone buffer is introduced, with a varying unequal protection policy in each zone. Application of this policy together with adaptive modulation results in up to 4 dB improvement in objective video quality compared to fixed rate scheme for an additive white Gaussian noise channel and around 10 dB for a Gilbert-Elliott channel. The paper also reports a consistent improvement in video quality over a scheme that adapts to channel conditions by varying the data rate without accounting for the video frame packet type or buffer congestion.

  9. A Comparative Analysis of Family Adaptability and Cohesion Ratings among Traumatized Urban Youth

    Science.gov (United States)

    Bellantuono, Alessandro; Saigh, Philip A.; Durham, Katherine; Dekis, Constance; Hackler, Dusty; McGuire, Leah A.; Yasik, Anastasia E.; Halamandaris, Phill V.; Oberfield, Richard A.

    2018-01-01

    Objective: Given the need to identify psychological risk factors among traumatized youth, this study examined the family functioning of traumatized youth with or without PTSD and a nonclinical sample. Method: The Family Adaptability and Cohesion Evaluation Scales, second edition (FACES II; Olson, Portner, & Bell, 1982), scores of youth with…

  10. Diversification rates indicate an early role of adaptive radiations at the origin of modern echinoid fauna.

    Directory of Open Access Journals (Sweden)

    Simon Boivin

    Full Text Available Evolutionary radiations are fascinating phenomena corresponding to a dramatic diversification of taxa and a burst of cladogenesis over short periods of time. Most evolutionary radiations have long been regarded as adaptive but this has seldom been demonstrated with large-scale comparative datasets including fossil data. Originating in the Early Jurassic, irregular echinoids are emblematic of the spectacular diversification of mobile marine faunas during the Mesozoic Marine Revolution. They diversified as they colonized various habitats, and now constitute the main component of echinoid fauna in modern seas. The evolutionary radiation of irregular echinoids has long been considered as adaptive but this hypothesis has never been tested. In the present work we analyze the evolution of echinoid species richness and morphological disparity over 37 million years based on an extensive fossil dataset. Our results demonstrate that morphological and functional diversifications in certain clades of irregular echinoids were exceptionally high compared to other clades and that they were associated with the evolution of new modes of life and so can be defined as adaptive radiations. The role played by ecological opportunities in the diversification of these clades was critical, with the evolution of the infaunal mode of life promoting the adaptive radiation of irregular echinoids.

  11. Mutation rate switch inside Eurasian mitochondrial haplogroups: impact of selection and consequences for dating settlement in Europe.

    Directory of Open Access Journals (Sweden)

    Denis Pierron

    Full Text Available R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America. This lineage played a major role in migration "out of Africa" and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1 sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario.

  12. Multi-rate cubature Kalman filter based data fusion method with residual compensation to adapt to sampling rate discrepancy in attitude measurement system.

    Science.gov (United States)

    Guo, Xiaoting; Sun, Changku; Wang, Peng

    2017-08-01

    This paper investigates the multi-rate inertial and vision data fusion problem in nonlinear attitude measurement systems, where the sampling rate of the inertial sensor is much faster than that of the vision sensor. To fully exploit the high frequency inertial data and obtain favorable fusion results, a multi-rate CKF (Cubature Kalman Filter) algorithm with estimated residual compensation is proposed in order to adapt to the problem of sampling rate discrepancy. During inter-sampling of slow observation data, observation noise can be regarded as infinite. The Kalman gain is unknown and approaches zero. The residual is also unknown. Therefore, the filter estimated state cannot be compensated. To obtain compensation at these moments, state error and residual formulas are modified when compared with the observation data available moments. Self-propagation equation of the state error is established to propagate the quantity from the moments with observation to the moments without observation. Besides, a multiplicative adjustment factor is introduced as Kalman gain, which acts on the residual. Then the filter estimated state can be compensated even when there are no visual observation data. The proposed method is tested and verified in a practical setup. Compared with multi-rate CKF without residual compensation and single-rate CKF, a significant improvement is obtained on attitude measurement by using the proposed multi-rate CKF with inter-sampling residual compensation. The experiment results with superior precision and reliability show the effectiveness of the proposed method.

  13. Adaptation to the aquatic environment: from penguin heart rates to cetacean brain morphology

    OpenAIRE

    Wright, Alexandra

    2016-01-01

    The evolutionary process of adaptation to the aquatic environment has dramatically modified the anatomy and physiology of secondarily-aquatic, air-breathing seabirds and marine mammals to address oxygen constraints and unique sensorimotor conditions. As taxa that have arguably undergone significant evolutionary transformations, deep-diving sphenisciforms (penguins) and obligatorily aquatic cetaceans (whales, dolphins, and porpoises) provide an excellent opportunity to study such physiological...

  14. Effect of Salinity Adaptation Technique on Survival and Growth Rate of Patin Catfish, Pangasius sp.

    Directory of Open Access Journals (Sweden)

    K. Nirmala

    2007-01-01

    Full Text Available This study was carried out to determine the effect of salinity adaptation techniques on growth and survival of patin catfish Pangasius sp. fry.  Fry of 1.5-2.0 inch in length were reared in the water with different of the initial salinity of 1, 2, 3, 4 and 5 ppt.  Salinity was then daily increased by duplicated the initial water salinity until fish died.  The results of study showed that fry could survive by initial salinity adaptation of 1 ppt and then increasing the salinity by 1 ppt/day to reach 27 ppt.  In the other treatments, all fry died after the salinity reach 18-25 ppt. Keywords: patin catfish, Pangasius, adaptation, salinity   ABSTRAK Penelitian ini bertujuan untuk mengetahui pengaruh teknik adaptasi salinitas terhadap pertumbuhan dan kelangsungan hidup benih ikan patin Pangasius sp.  Benih patin ukuran 1,5-2 inci dipelihara pada salinitas awal berbeda, yaitu 1, 2, 3, 4 dan 5 ppt. Salinitas air pemeliharaan ditingkatkan kelipatan dari salinitas awal setiap hari hingga ikan mati.  Hasil penelitian menunjukkan bahwa adaptasi salinitas awal 1 ppt dan peningkatan sebesar 1ppt/hari menyebabkan ikan dapat bertahan hidup sampai pada salinitas 27 ppt. Pada perlakuan lainnya, benih ikan mengalami kematian masal ketika salinitas mencapai 18-25 ppt. Kata kunci: ikan patin, Pangasius, adaptasi, salinitas

  15. Adaptive radiation along a thermal gradient: preliminary results of habitat use and respiration rate divergence among whitefish morphs.

    Directory of Open Access Journals (Sweden)

    Kimmo Kalevi Kahilainen

    Full Text Available Adaptive radiation is considered an important mechanism for the development of new species, but very little is known about the role of thermal adaptation during this process. Such adaptation should be especially important in poikilothermic animals that are often subjected to pronounced seasonal temperature variation that directly affects metabolic function. We conducted a preliminary study of individual lifetime thermal habitat use and respiration rates of four whitefish (Coregonus lavaretus (L. morphs (two pelagic, one littoral and one profundal using stable carbon and oxygen isotope values of otolith carbonate. These morphs, two of which utilized pelagic habitats, one littoral and one profundal recently diverged via adaptive radiation to exploit different major niches in a deep and thermally stratified subarctic lake. We found evidence that the morphs used different thermal niches. The profundal morph had the most distinct thermal niche and consistently occupied the coldest thermal habitat of the lake, whereas differences were less pronounced among the shallow water pelagic and littoral morphs. Our results indicated ontogenetic shifts in thermal niches: juveniles of all whitefish morphs inhabited warmer ambient temperatures than adults. According to sampling of the otolith nucleus, hatching temperatures were higher for benthic compared to pelagic morphs. Estimated respiration rate was the lowest for benthivorous profundal morph, contrasting with the higher values estimated for the other morphs that inhabited shallower and warmer water. These preliminary results suggest that physiological adaptation to different thermal habitats shown by the sympatric morphs may play a significant role in maintaining or strengthening niche segregation and divergence in life-history traits, potentially contributing to reproductive isolation and incipient speciation.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Adaptation and validation of a Spanish-language version of the Frontotemporal Dementia Rating Scale (FTD-FRS).

    Science.gov (United States)

    Turró-Garriga, O; Hermoso Contreras, C; Olives Cladera, J; Mioshi, E; Pelegrín Valero, C; Olivera Pueyo, J; Garre-Olmo, J; Sánchez-Valle, R

    2017-06-01

    The Frontotemporal Dementia Rating Scale (FTD-FRS) is a tool designed to aid with clinical staging and assessment of the progression of frontotemporal dementia (FTD-FRS). Present a multicentre adaptation and validation study of a Spanish version of the FRS. The adapted version was created using 2 translation-back translation processes (English to Spanish, Spanish to English) and verified by the scale's original authors. We validated the adapted version in a sample of consecutive patients diagnosed with FTD. The procedure included evaluating internal consistency, testing unidimensionality with the Rasch model, analysing construct validity and discriminant validity, and calculating the degree of agreement between the Clinical Dementia Rating scale (CDR) and FTD-FRS for FTD cases. The study included 60 patients with DFT. The mean score on the FRS was 12.1 points (SD=6.5; range, 2-25) with inter-group differences (F=120.3; df=3; Pde Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. 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

  20. 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.

  1. Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS

    Directory of Open Access Journals (Sweden)

    Thais Bento Lima-Silva

    Full Text Available ABSTRACT Background: Staging scales for dementia have been devised for grading Alzheimer's disease (AD but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD. Objective: To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS to Brazilian Portuguese. Methods: The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators, discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0. The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R, Mini-Mental State Examination (MMSE, Executive Interview (EXIT-25, Neuropsychiatric Inventory (NPI, Frontotemporal Dementia Rating Scale (FTD-FRS and Clinical Dementia Rating scale (CDR. Results: The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate. It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0 in fact had moderate or severe levels of disability according to the FTD-FRS. Conclusion: The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression.

  2. Physiological and performance adaptations to an in-season soccer camp in the heat: Associations with heart rate and heart rate variability

    DEFF Research Database (Denmark)

    Buchheit, M; Voss, S C; Nybo, Lars

    2011-01-01

    The aim of the present study was to examine the associations between adaptive responses to an in-season soccer training camp in the heat and changes in submaximal exercising heart rate (HRex, 5-min run at 9 ¿km/h), postexercise HR recovery (HRR) and HR variability (HRV). Fifteen well-trained but ......The aim of the present study was to examine the associations between adaptive responses to an in-season soccer training camp in the heat and changes in submaximal exercising heart rate (HRex, 5-min run at 9 ¿km/h), postexercise HR recovery (HRR) and HR variability (HRV). Fifteen well......-trained but non-heat-acclimatized male adult players performed a training week in Qatar (34.6¿±¿1.9°C wet bulb globe temperature). HRex, HRR, HRV (i.e. the standard deviation of instantaneous beat-to-beat R-R interval variability measured from Poincaré plots SD1, a vagal-related index), creatine kinase (CK...... at the beginning and at the end of the training week. Throughout the intervention, HRex and HRV showed decreasing (P¿...

  3. An adaptation method to improve secret key rates of time-frequency QKD in atmospheric turbulence channels

    Science.gov (United States)

    Sun, Xiaole; Djordjevic, Ivan B.; Neifeld, Mark A.

    2016-03-01

    Free-space optical (FSO) channels can be characterized by random power fluctuations due to atmospheric turbulence, which is known as scintillation. Weak coherent source based FSO quantum key distribution (QKD) systems suffer from the scintillation effect because during the deep channel fading the expected detection rate drops, which then gives an eavesdropper opportunity to get additional information about protocol by performing photon number splitting (PNS) attack and blocking single-photon pulses without changing QBER. To overcome this problem, in this paper, we study a large-alphabet QKD protocol, which is achieved by using pulse-position modulation (PPM)-like approach that utilizes the time-frequency uncertainty relation of the weak coherent photon state, called here TF-PPM-QKD protocol. We first complete finite size analysis for TF-PPM-QKD protocol to give practical bounds against non-negligible statistical fluctuation due to finite resources in practical implementations. The impact of scintillation under strong atmospheric turbulence regime is studied then. To overcome the secure key rate performance degradation of TF-PPM-QKD caused by scintillation, we propose an adaptation method for compensating the scintillation impact. By changing source intensity according to the channel state information (CSI), obtained by classical channel, the adaptation method improves the performance of QKD system with respect to the secret key rate. The CSI of a time-varying channel can be predicted using stochastic models, such as autoregressive (AR) models. Based on the channel state predictions, we change the source intensity to the optimal value to achieve a higher secret key rate. We demonstrate that the improvement of the adaptation method is dependent on the prediction accuracy.

  4. A Cost-Based Adaptive Handover Hysteresis Scheme to Minimize the Handover Failure Rate in 3GPP LTE System

    Directory of Open Access Journals (Sweden)

    Gil Gye-Tae

    2010-01-01

    Full Text Available We deal with a cost-based adaptive handover hysteresis scheme for the horizontal handover decision strategies, as one of the self-optimization techniques that can minimize the handover failure rate (HFR in the 3rd generation partnership project (3GPP long-term evolution (LTE system based on the network-controlled hard handover. Especially, for real-time operation, we propose an adaptive hysteresis scheme with a simplified cost function considering some dominant factors closely related to HFR performance such as the load difference between the target and serving cells, the velocity of user equipment (UE, and the service type. With the proposed scheme, a proper hysteresis value based on the dominant factors is easily obtained, so that the handover parameter optimization for minimizing the HFR can be effectively achieved. Simulation results show that the proposed scheme can support better HFR performance than the conventional schemes.

  5. Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

    International Nuclear Information System (INIS)

    Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

    2007-01-01

    To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

  6. Multi-rate sensor fusion-based adaptive discrete finite-time synergetic control for flexible-joint mechanical systems

    International Nuclear Information System (INIS)

    Xue Guang-Yue; Ren Xue-Mei; Xia Yuan-Qing

    2013-01-01

    This paper proposes an adaptive discrete finite-time synergetic control (ADFTSC) scheme based on a multi-rate sensor fusion estimator for flexible-joint mechanical systems in the presence of unmeasured states and dynamic uncertainties. Multi-rate sensors are employed to observe the system states which cannot be directly obtained by encoders due to the existence of joint flexibilities. By using an extended Kalman filter (EKF), the finite-time synergetic controller is designed based on a sensor fusion estimator which estimates states and parameters of the mechanical system with multi-rate measurements. The proposed controller can guarantee the finite-time convergence of tracking errors by the theoretical derivation. Simulation and experimental studies are included to validate the effectiveness of the proposed approach. (general)

  7. Adaptive super twisting vibration control of a flexible spacecraft with state rate estimation

    Science.gov (United States)

    Malekzadeh, Maryam; Karimpour, Hossein

    2018-05-01

    The robust attitude and vibration control of a flexible spacecraft trying to perform accurate maneuvers in spite of various sources of uncertainty is addressed here. Difficulties for achieving precise and stable pointing arise from noisy onboard sensors, parameters indeterminacy, outer disturbances as well as un-modeled or hidden dynamics interactions. Based on high-order sliding-mode methods, the non-minimum phase nature of the problem is dealt with through output redefinition. An adaptive super-twisting algorithm (ASTA) is incorporated with its observer counterpart on the system under consideration to get reliable attitude and vibration control in the presence of sensor noise and momentum coupling. The closed-loop efficiency is verified through simulations under various indeterminate situations and got compared to other methods.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Specific-locus mutation frequencies in mouse stem-cell spermatogonia at very low radiation dose rates, and their use in the estimation of genetic hazards of radiation in man

    International Nuclear Information System (INIS)

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

    1982-01-01

    Experiments were undertaken to augment the information on the lowest radiation dose rates feasible for scoring transmitted induced mutations detected by the specific-locus method in the mouse. This is the type of information most suitable for estimating genetic hazards of radiation in man. The results also aid in resolving conflicting possibilities about the relationship between mutation frequency and radiation dose at low dose rates

  10. [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.

  11. Different transcriptional responses from slow and fast growth rate strains of Listeria monocytogenes adapted to low temperature

    Directory of Open Access Journals (Sweden)

    Ninoska eCordero

    2016-03-01

    Full Text Available Listeria monocytogenes has become one of the principal foodborne pathogens worldwide. The capacity of this bacterium to grow at low temperatures has opened an interesting field of study in terms of the identification and classification of new strains of L. monocytogenes with different growth capacities at low temperatures. We determined the growth rate at 8 ºC of 110 strains of L. monocytogenes isolated from different food matrices. We identified a group of slow and fast strains according to their growth rate at 8 °C and performed a global transcriptomic assay in strains previously adapted to low temperature. We then identified shared and specific transcriptional mechanisms, metabolic and cellular processes of both groups; bacterial motility was the principal process capable of differentiating the adaptation capacity of L. monocytogenes strains with different ranges of tolerance to low temperatures. Strains belonging to the fast group were less motile, which may allow these strains to achieve a greater rate of proliferation at low temperature.

  12. A Rate-Adaptive MAC Protocol Based on TCP throughput for Ad Hoc Networks in Fading Channels

    Directory of Open Access Journals (Sweden)

    Shoko Uchida

    2008-10-01

    Full Text Available Wireless technology is becoming a leading option for future Internet access. Transmission Control Protocol (TCP is one of the protocols designed on the basis of the transmission characteristics in wired networks. It is known that the TCP performance deteriorates drastically under a wireless communication environment. On the other hand, many wireless networking standards such as IEEE 802.11a, 802.11b, and 802.11g have multirate capability. Therefore, adaptive rate control methods have been proposed for ad hoc networks. However, almost methods require the modification of the request to send (RTS and clear to send (CTS packets. Therefore, the conventional methods are not compatible with the standardized system. In this paper, we propose adaptive rate control mechanisms for ad hoc networks. Our mechanisms are based on the RTS/CTS mechanisms. However, no modifications to the RTS and CTS packets are required in the proposed method. Therefore, our proposed method can attempt to satisfy the conventional IEEE 802.11 standards. Moreover, an adequate transmission rate is selected based on an estimated TCP throughput performance. From simulation results, it is observed that the proposed method can improve the throughput performance without any modification of packet structures.

  13. 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.

  14. 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.

  15. Specific-locus experiments show that female mice exposed near the time of birth to low-LET ionizing radiation exhibit both a low mutational response and a dose-rate effect

    International Nuclear Information System (INIS)

    Selby, P.B.; Lee, S.S.; Kelly, E.M.; Bangham, J.W.; Raymer, G.D.; Hunsicker, P.R.

    1991-01-01

    Female mice were exposed to 300 R of 73-93 R/min X-radiation either as fetuses at 18.5d post conception (p.c.) or within 9h after birth. Combining the similar results from these 2 groups yielded a specific-locus mutation frequency of 9.4x10 -8 mutation/locus/R, which is statistically significantly higher than the historical-control mutation frequency, but much lower than the rate obtained by irradiating mature and maturing oocytes in adults. Other females, exposed at 18.5 days p.c. to 300 R of 0.79 R/min γ-radiation, yielded a mutation frequency that was statistically significantly lower than the frequency at high dose rates. The low-dose-rate group also had markedly higher fertility. It appears that the doe-rate effect for mutations induced near the time of birth may be more pronounced than that reported for mature and maturing oocytes of adults. A hypothesis sometimes advanced to explain low mutation frequencies recovered from cell populations that experience considerable radiation-induced cell killing is that there is selection against mutant cells. The reason for the relatively low mutational response following acute irradiation in the experiments is unknown; however, the finding of a dose-rate effect in these oocytes in the presence of only minor radiation-induced cell killing (as judged from fertility) makes it seem unlikely that selection was responsible for the low mutational response following acute exposure. Had selection been an important factor, the mutation frequency should have increased when oocyte killing was markedly reduced. (author). 32 refs.; 5 figs.; 5 tabs

  16. Adaptation of the Rating Scale Mental Effort (RSME) for use in Indonesia

    NARCIS (Netherlands)

    Widyanti, Ari; Johnson, Addie; de Waard, Dick

    The Rating Scale Mental Effort (RSME) is a unidimensional instrument used to measure subjective mental workload. The RSME consists of a line with a length of 150 mm marked with nine anchor points, each accompanied by a descriptive label indicating a degree of effort. The RSME has been widely used in

  17. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

    Science.gov (United States)

    Hursel, Rick; Martens, Eveline A P; Gonnissen, Hanne K J; Hamer, Henrike M; Senden, Joan M G; van Loon, Luc J C; Westerterp-Plantenga, Margriet S

    2015-01-01

    Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;Pprotein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;Psynthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;Pprotein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and

  18. Suppression of carcinogenesis in mice by adaptive responses to low dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Kazuo; Iwasaki, Toshiyasu; Hoshi, Yuko; Nomura, Takaharu; Ina, Yasuhiro; Tanooka, Hiroshi [Central Research Institute of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

    2003-07-01

    Effects of prolonged low-dose-rate irradiation on the process of carcinogenesis were examined in mice treated with chemical carcinogen or irradiated with high doses of X-rays. Female ICR mice, 5 week-old, 35 in each group, were exposed to gamma-rays from a {sup 137}Cs source in the long-term low dose rate irradiation facility at CRIEPI. The dose rate was 2.6 mGy/hr (A), 0.96 mGy/hr (B), or 0.30 mGy/hr (C). Thirty-five days later, the mice were injected into the groin with 0.5 mg of methylcholanthrene (MC) dissolved in olive oil and irradiation was continued. Cumulative tumor incidences after 216 days following MC injection were 89% in group A, 76% in group B, and 94% in group C. That in non-irradiated control group was 94%. The difference in the tumor incidence between the control and position B was statistically significant, indicating the suppressive effect of the low dose rate irradiation on the process of MC-induced carcinogenesis with an optimum dose rate around 1 mGy/hr. In B6C3F1 mice, although the suppression of tumor incidence was not observed, there was a significant delay in tumor appearance in the irradiated mice between 100-150 days after MC injection. A group of 20 female C57BL/6N mice, 5 weeks old, were exposed to gamma-rays at 0.95 mGy/hr for 5 weeks. Then, they were exposed weekly to 1.8 Gy whole body X-irradiation (300 kVp) for consecutive 4 weeks to induce thymic lymphoma. Another group received only the fractionated irradiation. The first mouse died from thymic lymphoma appeared 89 days after the last irradiation in the group received only the fractionated irradiation, while 110 days in the group combined with the low dose rate irradiation. (author)

  19. How low can you go? An adaptive energetic framework for interpreting basal metabolic rate variation in endotherms.

    Science.gov (United States)

    Swanson, David L; McKechnie, Andrew E; Vézina, François

    2017-12-01

    Adaptive explanations for both high and low body mass-independent basal metabolic rate (BMR) in endotherms are pervasive in evolutionary physiology, but arguments implying a direct adaptive benefit of high BMR are troublesome from an energetic standpoint. Here, we argue that conclusions about the adaptive benefit of BMR need to be interpreted, first and foremost, in terms of energetics, with particular attention to physiological traits on which natural selection is directly acting. We further argue from an energetic perspective that selection should always act to reduce BMR (i.e., maintenance costs) to the lowest level possible under prevailing environmental or ecological demands, so that high BMR per se is not directly adaptive. We emphasize the argument that high BMR arises as a correlated response to direct selection on other physiological traits associated with high ecological or environmental costs, such as daily energy expenditure (DEE) or capacities for activity or thermogenesis. High BMR thus represents elevated maintenance costs required to support energetically demanding lifestyles, including living in harsh environments. BMR is generally low under conditions of relaxed selection on energy demands for high metabolic capacities (e.g., thermoregulation, activity) or conditions promoting energy conservation. Under these conditions, we argue that selection can act directly to reduce BMR. We contend that, as a general rule, BMR should always be as low as environmental or ecological conditions permit, allowing energy to be allocated for other functions. Studies addressing relative reaction norms and response times to fluctuating environmental or ecological demands for BMR, DEE, and metabolic capacities and the fitness consequences of variation in BMR and other metabolic traits are needed to better delineate organismal metabolic responses to environmental or ecological selective forces.

  20. Adaptive heart rate-based epileptic seizure detection using real-time user feedback

    DEFF Research Database (Denmark)

    De Cooman, Thomas; Kjær, Troels Wesenberg; Van Huffel, Sabine

    2017-01-01

    Automated seizure detection in a home environment has been of increased interest the last couple of decades. Heart rate-based seizure detection is a way to detect temporal lobe epilepsy seizures at home, but patient-independent algorithms showed to be insufficiently accurate due to the high patient...... with incorrect user feedback, making it ideal for implementation in a home environment for a seizure warning system....

  1. Increase in Multicast OFDM Data Rate in PLC Network using Adaptive LP-OFDM

    OpenAIRE

    Maiga , Ali; Baudais , Jean-Yves; Hélard , Jean-François

    2009-01-01

    ISBN: 978-1-4244-3523-4; International audience; Linear precoding (LP) technique applied to OFDM systems has already proved its ability to significantly increase the system throughput in a powerline communication (PLC) context. In this paper, we propose resource allocation algorithms based on the LP technique to increase the multicast OFDM systems bit rate. The conventional multicast capacity is limited by the user which experiences the worst channel conditions. To increase the multicast bit ...

  2. A Fair Adaptive Data Rate Algorithm for LoRaWAN

    OpenAIRE

    Abdelfadeel, Khaled Q.; Cionca, Victor; Pesch, Dirk

    2018-01-01

    LoRaWAN exhibits several characteristics that can lead to an unfair distribution of the Data Extracted Rate (DER) among nodes. Firstly, the capture effect leads to a strong signal suppressing a weaker signal at the gateway and secondly, the spreading codes used are not perfectly orthogonal, causing packet loss if an interfering signal is strong enough. In these conditions, nodes experiencing higher attenuation are less likely to see their packets received correctly. We develop FADR, a Fair Ad...

  3. Content-Aware Scalability-Type Selection for Rate Adaptation of Scalable Video

    Directory of Open Access Journals (Sweden)

    Tekalp A Murat

    2007-01-01

    Full Text Available Scalable video coders provide different scaling options, such as temporal, spatial, and SNR scalabilities, where rate reduction by discarding enhancement layers of different scalability-type results in different kinds and/or levels of visual distortion depend on the content and bitrate. This dependency between scalability type, video content, and bitrate is not well investigated in the literature. To this effect, we first propose an objective function that quantifies flatness, blockiness, blurriness, and temporal jerkiness artifacts caused by rate reduction by spatial size, frame rate, and quantization parameter scaling. Next, the weights of this objective function are determined for different content (shot types and different bitrates using a training procedure with subjective evaluation. Finally, a method is proposed for choosing the best scaling type for each temporal segment that results in minimum visual distortion according to this objective function given the content type of temporal segments. Two subjective tests have been performed to validate the proposed procedure for content-aware selection of the best scalability type on soccer videos. Soccer videos scaled from 600 kbps to 100 kbps by the proposed content-aware selection of scalability type have been found visually superior to those that are scaled using a single scalability option over the whole sequence.

  4. Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells

    NARCIS (Netherlands)

    Michaelis, M.; Rothweiler, F.; Barth, S.; Cinatl, J.; van Rikxoort, M.; Loeschmann, N.; Voges, Y.; Breitling, R.; von Deimling, A.; Roedel, F.; Weber, K.; Fehse, B.; Mack, E.; Stiewe, T.; Doerr, H. W.; Speidel, D.; Cinatl, J.; Cinatl jr., J.; Stephanou, A.

    2011-01-01

    Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines

  5. Adaptive Support Ventilation May Deliver Unwanted Respiratory Rate-Tidal Volume Combinations in Patients with Acute Lung Injury Ventilated According to an Open Lung Concept

    NARCIS (Netherlands)

    Dongelmans, Dave A.; Paulus, Frederique; Veelo, Denise P.; Binnekade, Jan M.; Vroom, Margreeth B.; Schultz, Marcus J.

    2011-01-01

    Background: With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury.

  6. Bacterias con alta tasa de mutación: los riesgos de una vida acelerada High mutation rate bacteria: Risks of a high-speed life

    Directory of Open Access Journals (Sweden)

    JUAN CARLOS GALÁN

    2006-03-01

    Full Text Available El proceso evolutivo de un ser vivo se acelera cuanto mayor sea su capacidad para producir variabilidad genética, bien por mutación, bien por recombinación. Sin embargo, cuanto mayor sea esta capacidad, mayor también será el riesgo de acumular mutaciones del etéreas. La variabilidad genética es, por tanto, un proceso altamente regulado, de tal manera que las bacterias tienden a mantener una baja tasa de mutación. En diferentes poblaciones bacterianas analizadas hay siempre un porcentaje variable de cepas con una tasa de mutación superior a la frecuencia modal del resto de la población. Existe una relación directa entre la proporción de cepas que mutan y el grado de estrés del ambiente. Así, en los procesos infecciosos crónicos, en los que el tratamiento antibiótico es constante durante períodos prolongados, se observan los mayores porcentajes de bacterias que mutan, cercano al 50% de la población. Esta selección positiva de bacterias que mutan es debida al enorme potencial que presentan para desarrollar resistencia antibiótica (100 veces superior a una bacteria normal. Esta capacidad ha sido explotada, en algunos centros de investigación, como un modelo natural de evolución acelerada para predecir la facilidad con la que determinadas variantes resistentes pueden aparecer, saber qué posiciones serán las más susceptibles a los cambios y cuál será el costo para la bacteria. El laboratorio de microbiología debe hacer un esfuerzo por detectar estas cepas mutadoras antes de que desarrollen mecanismos de resistencia e induzcan el fracaso terapéutico.The potential of producing genetic variability, either by mutation or by recombination, is the driving force of evolution in a living organism. Genetic variability is a quite regulated process in which bacteria tend to maintain a low mutation rate. However, a variable proportion of bacteria with a higher mutation rate than that of the modal is always present in any population

  7. Testing an Adapted Modified Delphi Method: Synthesizing Multiple Stakeholder Ratings of Health Care Service Effectiveness.

    Science.gov (United States)

    Escaron, Anne L; Chang Weir, Rosy; Stanton, Petra; Vangala, Sitaram; Grogan, Tristan R; Clarke, Robin M

    2016-03-01

    The Affordable Care Act incentivizes health systems for better meeting patient needs, but often guidance about patient preferences for particular health services is limited. All too often vulnerable patient populations are excluded from these decision-making settings. A community-based participatory approach harnesses the in-depth knowledge of those experiencing barriers to health care. We made three modifications to the RAND-UCLA appropriateness method, a modified Delphi approach, involving patients, adding an advisory council group to characterize existing knowledge in this little studied area, and using effectiveness rather than "appropriateness" as the basis for rating. As a proof of concept, we tested this method by examining the broadly delivered but understudied nonmedical services that community health centers provide. This method created discrete, new knowledge about these services by defining 6 categories and 112 unique services and by prioritizing among these services based on effectiveness using a 9-point scale. Consistent with the appropriateness method, we found statistical convergence of ratings among the panelists. Challenges include time commitment and adherence to a clear definition of effectiveness of services. This diverse stakeholder engagement method efficiently addresses gaps in knowledge about the effectiveness of health care services to inform population health management. © 2015 Society for Public Health Education.

  8. A transcription factor links growth rate and metabolism in the hypersaline adapted archaeon Halobacterium salinarum.

    Science.gov (United States)

    Todor, Horia; Dulmage, Keely; Gillum, Nicholas; Bain, James R; Muehlbauer, Michael J; Schmid, Amy K

    2014-09-01

    Co-ordinating metabolism and growth is a key challenge for all organisms. Despite fluctuating environments, cells must produce the same metabolic outputs to thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria and eukaryotes, but remain unexplored in archaea. In the model archaeon Halobacterium salinarum, the transcription factor TrmB regulates enzyme-coding genes in diverse metabolic pathways in response to glucose. However, H. salinarum is thought not to catabolize glucose. To resolve this discrepancy, we demonstrate that TrmB regulates the gluconeogenic production of sugars incorporated into the cell surface S-layer glycoprotein. Additionally, we show that TrmB-DNA binding correlates with instantaneous growth rate, likely because S-layer glycosylation is proportional to growth. This suggests that TrmB transduces a growth rate signal to co-regulated metabolic pathways including amino acid, purine, and cobalamin biosynthesis. Remarkably, the topology and function of this growth homeostatic network appear conserved across domains despite extensive alterations in protein components. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  9. Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

    Science.gov (United States)

    Dudley, Matthew Z.; Sheen, Patricia; Gilman, Robert H.; Ticona, Eduardo; Friedland, Jon S.; Kirwan, Daniela E.; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z.; Coronel, Jorge; Grandjean, Louis; Moore, David A. J.; Evans, Carlton A.; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

    2016-01-01

    Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. PMID:27928075

  10. Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: low rate of 23S rRNA mutations in Enterococcus faecium.

    Science.gov (United States)

    Lee, Sae-Mi; Huh, Hee Jae; Song, Dong Joon; Shim, Hyang Jin; Park, Kyung Sun; Kang, Cheol-In; Ki, Chang-Seok; Lee, Nam Yong

    2017-12-01

    To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Enterococcal isolates exhibiting linezolid MICs ≥4 mg l -1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes.Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1 % (34/87) of E. faecium and 18.8 % (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70 % (7/10) linezolid-resistant and 30 % (3/10) linezolid-intermediate] and three E. faecium [33.3 % (1/3) linezolid-resistant and 66.7 % (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4 % (10/14) linezolid-resistant and 28.6 % (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6 % (23/34) of linezolid-resistant E. faecium. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.

  11. Cross-cultural adaptation and validation of als Functional Rating Scale-Revised in Portuguese language.

    Science.gov (United States)

    Guedes, Keyte; Pereira, Cecília; Pavan, Karina; Valério, Berenice Cataldo Oliveira

    2010-02-01

    The aim of this study is the cross-cultural, as well as to validate in Portuguese language the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). We performed a prospective study of individuals with amyotrophic lateral sclerosis (ALS) clinically defined. The scale, after obtaining the final version in Portuguese, was administered in 22 individuals and three weeks after re-applied. There were no significant differences between the application and reapplication of the scale (p=0.069). The linear regression and internal consistency measured by Pearson correlation and alpha Conbrach were significant with r=0.975 e alpha=0.934. The reliability test-retest demonstrated by intraclass correlation coefficient was strong with ICC=0.975. Therefore, this version proved to be applicable, reliable and easy to be conducted in clinical practice and research.

  12. Assessment of fusion facility dose rate map using mesh adaptivity enhancements of hybrid Monte Carlo/deterministic techniques

    International Nuclear Information System (INIS)

    Ibrahim, Ahmad M.; Wilson, Paul P.; Sawan, Mohamed E.; Mosher, Scott W.; Peplow, Douglas E.; Grove, Robert E.

    2014-01-01

    Highlights: •Calculate the prompt dose rate everywhere throughout the entire fusion energy facility. •Utilize FW-CADIS to accurately perform difficult neutronics calculations for fusion energy systems. •Develop three mesh adaptivity algorithms to enhance FW-CADIS efficiency in fusion-neutronics calculations. -- Abstract: Three mesh adaptivity algorithms were developed to facilitate and expedite the use of the CADIS and FW-CADIS hybrid Monte Carlo/deterministic techniques in accurate full-scale neutronics simulations of fusion energy systems with immense sizes and complicated geometries. First, a macromaterial approach enhances the fidelity of the deterministic models without changing the mesh. Second, a deterministic mesh refinement algorithm generates meshes that capture as much geometric detail as possible without exceeding a specified maximum number of mesh elements. Finally, a weight window coarsening algorithm decouples the weight window mesh and energy bins from the mesh and energy group structure of the deterministic calculations in order to remove the memory constraint of the weight window map from the deterministic mesh resolution. The three algorithms were used to enhance an FW-CADIS calculation of the prompt dose rate throughout the ITER experimental facility and resulted in a 23.3% increase in the number of mesh tally elements in which the dose rates were calculated in a 10-day Monte Carlo calculation. Additionally, because of the significant increase in the efficiency of FW-CADIS simulations, the three algorithms enabled this difficult calculation to be accurately solved on a regular computer cluster, eliminating the need for a world-class super computer

  13. Clinical Application of Screening for GJB2 Mutations before Cochlear Implantation in a Heterogeneous Population with High Rate of Autosomal Recessive Nonsyndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Masoud Motasaddi Zarandy

    2011-01-01

    Full Text Available Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs and speech recognition thresholds (SRTs improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all >0.10. Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, =0.22. Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.

  14. The experience of mutation rate quantitative evaluation in connection with environmental pollution (based on studies of congenital anomalies in human populations).

    Science.gov (United States)

    Antipenko YeN; Kogut, N N

    1993-10-01

    relation between average annual general emission of atmospheric pollutants (M./Z.) was 2.21, the frequency of dominant and X-linked CA 2.20 and of new skeleton mutations 2.24. The difference of mutation rate in the towns studied was due to the dynamics of demographic processes.

  15. Noiseless imaging detector for adaptive optics with kHz frame rates

    CERN Document Server

    Vallerga, J V; Mikulec, Bettina; Tremsin, A; Clark, Allan G; Siegmund, O H W; CERN. Geneva

    2004-01-01

    A new hybrid optical detector is described that has many of the attributes desired for the next generation AO wavefront sensors. The detector consists of a proximity focused MCP read out by four multi-pixel application specific integrated circuit (ASIC) chips developed at CERN (â€ワMedipix2”) with individual pixels that amplify, discriminate and count input events. The detector has 512 x 512 pixels, zero readout noise (photon counting) and can be read out at 1 kHz frame rates. The Medipix2 readout chips can be electronically shuttered down to a temporal window of a few microseconds with an accuracy of 10 nanoseconds. When used in a Shack-Hartman style wavefront sensor, it should be able to centroid approximately 5000 spots using 7 x 7 pixel sub-apertures resulting in very linear, off-null error correction terms. The quantum efficiency depends on the optical photocathode chosen for the bandpass of interest. A three year development effort for this detector technology has just been funded as part of the...

  16. Heart rate variability in prediction of individual adaptation to endurance training in recreational endurance runners.

    Science.gov (United States)

    Vesterinen, V; Häkkinen, K; Hynynen, E; Mikkola, J; Hokka, L; Nummela, A

    2013-03-01

    The aim of this study was to investigate whether nocturnal heart rate variability (HRV) can be used to predict changes in endurance performance during 28 weeks of endurance training. The training was divided into 14 weeks of basic training (BTP) and 14 weeks of intensive training periods (ITP). Endurance performance characteristics, nocturnal HRV, and serum hormone concentrations were measured before and after both training periods in 28 recreational endurance runners. During the study peak treadmill running speed (Vpeak ) improved by 7.5 ± 4.5%. No changes were observed in HRV indices after BTP, but after ITP, these indices increased significantly (HFP: 1.9%, P=0.026; TP: 1.7%, P=0.007). Significant correlations were observed between the change of Vpeak and HRV indices (TP: r=0.75, PHRV among recreational endurance runners, it seems that moderate- and high-intensity training are needed. This study showed that recreational endurance runners with a high HRV at baseline improved their endurance running performance after ITP more than runners with low baseline HRV. © 2011 John Wiley & Sons A/S.

  17. In vitro techniques for selection of radiation induced mutations adapted to adverse environmental conditions. Proceedings of a final research co-ordination meeting

    International Nuclear Information System (INIS)

    2001-06-01

    The ever increasing human population and dwindling land and water resources worldwide make it essential to produce more food, fibre and fodder from less and less land. During the last century, plant breeding contributed remarkably to increasing food by producing varieties which give higher yield, have improved quality and nutrition, and resist diseases and pests. Nearly 50% of the increase in food production in Asia during the last fifty years can be attributed to the high yielding, short height varieties of rice and wheat, the remaining to the improved agronomic inputs and management. Many crops, such as cassava, potato, pineapple, sweet potato, sugarcane, banana and plantain are major food crops, and others such as sugarcane and pineapple are important to the economies of many developing countries. One of the solutions to have a sustainable and secure food production is to breed varieties which are tolerant of stress conditions during their growth and development. Hence a Co-ordinated Research Project on In vitro Techniques for Selection of Radiation Induced Mutations Adapted to Adverse Environmental Conditions was initiated and focused primarily on the improvement of vegetatively propagated plants. Since the inception of this project, several participating scientists established the optimal dose requirement for in vitro cultured material. Investigations were carried out on the effect of radiation to alter traits which affect survival under stress conditions and high temperature stress in potato, pineapple, sweet potato and garlic. The possibility to change traits such as tolerance to saline and water logged soils in sugarcane and gene regulation for salinity tolerance were studied. The limited number of available reports suggest that callus cultures are much more sensitive to radiation treatment and require much lower doses (2 to 5 Gy) than stem cuttings or seeds, and that relatively higher doses (15 to 20 Gy) cause necrosis or loss of regenerative capacity. The

  18. In vitro techniques for selection of radiation induced mutations adapted to adverse environmental conditions. Proceedings of a final research co-ordination meeting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-06-01

    The ever increasing human population and dwindling land and water resources worldwide make it essential to produce more food, fibre and fodder from less and less land. During the last century, plant breeding contributed remarkably to increasing food by producing varieties which give higher yield, have improved quality and nutrition, and resist diseases and pests. Nearly 50% of the increase in food production in Asia during the last fifty years can be attributed to the high yielding, short height varieties of rice and wheat, the remaining to the improved agronomic inputs and management. Many crops, such as cassava, potato, pineapple, sweet potato, sugarcane, banana and plantain are major food crops, and others such as sugarcane and pineapple are important to the economies of many developing countries. One of the solutions to have a sustainable and secure food production is to breed varieties which are tolerant of stress conditions during their growth and development. Hence a Co-ordinated Research Project on In vitro Techniques for Selection of Radiation Induced Mutations Adapted to Adverse Environmental Conditions was initiated and focused primarily on the improvement of vegetatively propagated plants. Since the inception of this project, several participating scientists established the optimal dose requirement for in vitro cultured material. Investigations were carried out on the effect of radiation to alter traits which affect survival under stress conditions and high temperature stress in potato, pineapple, sweet potato and garlic. The possibility to change traits such as tolerance to saline and water logged soils in sugarcane and gene regulation for salinity tolerance were studied. The limited number of available reports suggest that callus cultures are much more sensitive to radiation treatment and require much lower doses (2 to 5 Gy) than stem cuttings or seeds, and that relatively higher doses (15 to 20 Gy) cause necrosis or loss of regenerative capacity. The

  19. Effects of Yoga on Stress, Stress Adaption, and Heart Rate Variability Among Mental Health Professionals--A Randomized Controlled Trial.

    Science.gov (United States)

    Lin, Shu-Ling; Huang, Ching-Ya; Shiu, Shau-Ping; Yeh, Shu-Hui

    2015-08-01

    Mental health professionals experiencing work-related stress may experience burn out, leading to a negative impact on their organization and patients. The aim of this study was to examine the effects of yoga classes on work-related stress, stress adaptation, and autonomic nerve activity among mental health professionals. A randomized controlled trial was used, which compared the outcomes between the experimental (e.g., yoga program) and the control groups (e.g., no yoga exercise) for 12 weeks. Work-related stress and stress adaptation were assessed before and after the program. Heart rate variability (HRV) was measured at baseline, midpoint through the weekly yoga classes (6 weeks), and postintervention (after 12 weeks of yoga classes). The results showed that the mental health professionals in the yoga group experienced a significant reduction in work-related stress (t = -6.225, p control group revealed no significant changes. Comparing the mean differences in pre- and posttest scores between yoga and control groups, we found the yoga group significantly decreased work-related stress (t = -3.216, p = .002), but there was no significant change in stress adaptation (p = .084). While controlling for the pretest scores of work-related stress, participants in yoga, but not the control group, revealed a significant increase in autonomic nerve activity at midpoint (6 weeks) test (t = -2.799, p = .007), and at posttest (12 weeks; t = -2.099, p = .040). Because mental health professionals experienced a reduction in work-related stress and an increase in autonomic nerve activity in a weekly yoga program for 12 weeks, clinicians, administrators, and educators should offer yoga classes as a strategy to help health professionals reduce their work-related stress and balance autonomic nerve activities. © 2015 The Authors. Worldviews on Evidence-Based Nursing published by Wiley Periodicals, Inc. on behalf of Society for Worldviews on Evidence-Based Nursing.

  20. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

    Directory of Open Access Journals (Sweden)

    Rick Hursel

    Full Text Available Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d or low protein (0.4 g protein/kg/d energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001. Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03, synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01 and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001 were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042

  1. Farsi version of social skills rating system-secondary student form: cultural adaptation, reliability and construct validity.

    Science.gov (United States)

    Eslami, Ahmad Ali; Amidi Mazaheri, Maryam; Mostafavi, Firoozeh; Abbasi, Mohamad Hadi; Noroozi, Ensieh

    2014-01-01

    Assessment of social skills is a necessary requirement to develop and evaluate the effectiveness of cognitive and behavioral interventions. This paper reports the cultural adaptation and psychometric properties of the Farsi version of the social skills rating system-secondary students form (SSRS-SS) questionnaire (Gresham and Elliot, 1990), in a normative sample of secondary school students. A two-phase design was used that phase 1 consisted of the linguistic adaptation and in phase 2, using cross-sectional sample survey data, the construct validity and reliability of the Farsi version of the SSRS-SS were examined in a sample of 724 adolescents aged from 13 to 19 years. Content validity index was excellent, and the floor/ceiling effects were low. After deleting five of the original SSRS-SS items, the findings gave support for the item convergent and divergent validity. Factor analysis revealed four subscales. RESULTS showed good internal consistency (0.89) and temporal stability (0.91) for the total scale score. Findings demonstrated support for the use of the 27-item Farsi version in the school setting. Directions for future research regarding the applicability of the scale in other settings and populations of adolescents are discussed.

  2. A model of curved saccade trajectories: spike rate adaptation in the brainstem as the cause of deviation away.

    Science.gov (United States)

    Kruijne, Wouter; Van der Stigchel, Stefan; Meeter, Martijn

    2014-03-01

    The trajectory of saccades to a target is often affected whenever there is a distractor in the visual field. Distractors can cause a saccade to deviate towards their location or away from it. The oculomotor mechanisms that produce deviation towards distractors have been thoroughly explored in behavioral, neurophysiological and computational studies. The mechanisms underlying deviation away, on the other hand, remain unclear. Behavioral findings suggest a mechanism of spatially focused, top-down inhibition in a saccade map, and deviation away has become a tool to investigate such inhibition. However, this inhibition hypothesis has little neuroanatomical or neurophysiological support, and recent findings go against it. Here, we propose that deviation away results from an unbalanced saccade drive from the brainstem, caused by spike rate adaptation in brainstem long-lead burst neurons. Adaptation to stimulation in the direction of the distractor results in an unbalanced drive away from it. An existing model of the saccade system was extended with this theory. The resulting model simulates a wide range of findings on saccade trajectories, including findings that have classically been interpreted to support inhibition views. Furthermore, the model replicated the effect of saccade latency on deviation away, but predicted this effect would be absent with large (400 ms) distractor-target onset asynchrony. This prediction was confirmed in an experiment, which demonstrates that the theory both explains classical findings on saccade trajectories and predicts new findings. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Application of multivariate adaptive regression spine-assisted objective function on optimization of heat transfer rate around a cylinder

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Prasenjit; Dad, Ajoy K. [Mechanical Engineering Department, National Institute of Technology, Agartala (India)

    2016-12-15

    The present study aims to predict the heat transfer characteristics around a square cylinder with different corner radii using multivariate adaptive regression splines (MARS). Further, the MARS-generated objective function is optimized by particle swarm optimization. The data for the prediction are taken from the recently published article by the present authors [P. Dey, A. Sarkar, A.K. Das, Development of GEP and ANN model to predict the unsteady forced convection over a cylinder, Neural Comput. Appl. (2015). Further, the MARS model is compared with artificial neural network and gene expression programming. It has been found that the MARS model is very efficient in predicting the heat transfer characteristics. It has also been found that MARS is more efficient than artificial neural network and gene expression programming in predicting the forced convection data, and also particle swarm optimization can efficiently optimize the heat transfer rate.

  4. Reducing Deadline Miss Rate for Grid Workloads running in Virtual Machines: a deadline-aware and adaptive approach

    CERN Document Server

    Khalid, Omer; Anthony, Richard; Petridis, Miltos

    2011-01-01

    This thesis explores three major areas of research; integration of virutalization into sci- entific grid infrastructures, evaluation of the virtualization overhead on HPC grid job’s performance, and optimization of job execution times to increase their throughput by reducing job deadline miss rate. Integration of the virtualization into the grid to deploy on-demand virtual machines for jobs in a way that is transparent to the end users and have minimum impact on the existing system poses a significant challenge. This involves the creation of virtual machines, decompression of the operating system image, adapting the virtual environ- ment to satisfy software requirements of the job, constant update of the job state once it’s running with out modifying batch system or existing grid middleware, and finally bringing the host machine back to a consistent state. To facilitate this research, an existing and in production pilot job framework has been modified to deploy virtual machines on demand on the grid using...

  5. Designing adaptive integral sliding mode control for heart rate regulation during cycle-ergometer exercise using bio-feedback.

    Science.gov (United States)

    Argha, Ahmadreza; Su, Steven W; Nguyen, Hung; Celler, Branko G

    2015-01-01

    This paper considers our developed control system which aims to regulate the exercising subjects' heart rate (HR) to a predefined profile. The controller would be an adaptive integral sliding mode controller. Here it is assumed that the controller commands are interpreted as biofeedback auditory commands. These commands can be heard and implemented by the exercising subject as a part of the control-loop. However, transmitting a feedback signal while the pedals are not in the appropriate position to efficiently exert force may lead to a cognitive disengagement of the user from the feedback controller. To address this problem this paper will employ a different form of control system regarding as "actuator-based event-driven control system". This paper will claim that the developed event-driven controller makes it possible to effectively regulate HR to a predetermined HR profile.

  6. Comparability of Mayo-Portland Adaptability Inventory ratings by staff, significant others and people with acquired brain injury.

    Science.gov (United States)

    Malec, James F

    2004-06-01

    To determine the internal consistency, reliability and comparability of the Mayo-Portland Adaptability Inventory (MPAI-4) and sub-scales completed by people with acquired brain injury (ABI), family and significant others (SO) and rehabilitation staff. 134 people with ABI consecutively seen for outpatient rehabilitation evaluation. MPAI-4 protocols based on independent ratings by the people with ABI undergoing evaluation, SO and rehabilitation staff were submitted to Rasch Facets analysis to determine the internal consistency of the overall measure and sub-scales (Ability, Adjustment and Participation indices) for each rater group and for a composite measure based on all rater groups. Rater agreement for individual items was also examined. Rasch indicators of internal consistency were entirely within acceptable limits for 3-rater composite full scale and sub-scale measures; these indicators were generally within acceptable limits for measures based on a single rater group. Item agreement was generally acceptable; disagreements suggested various sources of bias for specific rater groups. The MPAI-4 possesses satisfactory internal consistency regardless of rating source. A composite measure based on ratings made independently by people with ABI, SO and staff may serve as a 'gold standard' for research purposes. In the clinical setting, assessment of varying perspectives and biases may not only best represent outcome as evaluated by all parties involved but be essential to developing effective rehabilitation plans.

  7. A software reconfigurable optical multiband UWB system utilizing a bit-loading combined with adaptive LDPC code rate scheme

    Science.gov (United States)

    He, Jing; Dai, Min; Chen, Qinghui; Deng, Rui; Xiang, Changqing; Chen, Lin

    2017-07-01

    In this paper, an effective bit-loading combined with adaptive LDPC code rate algorithm is proposed and investigated in software reconfigurable multiband UWB over fiber system. To compensate the power fading and chromatic dispersion for the high frequency of multiband OFDM UWB signal transmission over standard single mode fiber (SSMF), a Mach-Zehnder modulator (MZM) with negative chirp parameter is utilized. In addition, the negative power penalty of -1 dB for 128 QAM multiband OFDM UWB signal are measured at the hard-decision forward error correction (HD-FEC) limitation of 3.8 × 10-3 after 50 km SSMF transmission. The experimental results show that, compared to the fixed coding scheme with the code rate of 75%, the signal-to-noise (SNR) is improved by 2.79 dB for 128 QAM multiband OFDM UWB system after 100 km SSMF transmission using ALCR algorithm. Moreover, by employing bit-loading combined with ALCR algorithm, the bit error rate (BER) performance of system can be further promoted effectively. The simulation results present that, at the HD-FEC limitation, the value of Q factor is improved by 3.93 dB at the SNR of 19.5 dB over 100 km SSMF transmission, compared to the fixed modulation with uncoded scheme at the same spectrum efficiency (SE).

  8. Combined non-adaptive light and smell stimuli lowered blood pressure, reduced heart rate and reduced negative affect.

    Science.gov (United States)

    Dong, Shan; Jacob, Tim J C

    2016-03-15

    Bright light therapy has been shown to have a positive impact on seasonal affective disorder (SAD), depression and anxiety. Smell has also has been shown to have effects on mood, stress, anxiety and depression. The objective of this study was to investigate the effect of the combination of light and smell in a non-adaptive cycle. Human subjects were given smell (lemon, lavender or peppermint) and light stimuli in a triangular wave (60scycle) for 15min. Blood pressure and heart rate were monitored before and after each session for 5 consecutive days and a Profile of Mood States (POMS) test was administered before and after the sensory stimulation on days 1, 3 and 5. The light-smell stimulus lowered blood pressure, both systolic and diastolic, and reduced heart rate for all odours compared to control. Of the two sensory stimuli, the odour stimulus contributed most to this effect. The different aromas in the light-smell combinations could be distinguished by their different effects on the mood factors with lemon inducing the greatest mood changes in Dejection-Depression, Anger-Hostility, Tension-Anxiety. In conclusion, combined light and smell stimulation was effective in lowering blood pressure, reducing heart rate and improving mood. The combination was more effective than either smell or light stimuli alone, suggesting that a light-smell combination would be a more robust and efficacious alternative treatment for depression, anxiety and stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  10. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  11. Cross-cultural adaptation and reliability and validity of the Dutch Patient-Rated Tennis Elbow Evaluation (PRTEE-D).

    Science.gov (United States)

    van Ark, Mathijs; Zwerver, Johannes; Diercks, Ronald L; van den Akker-Scheek, Inge

    2014-08-11

    Lateral Epicondylalgia (LE) is a common injury for which no reliable and valid measure exists to determine severity in the Dutch language. The Patient-Rated Tennis Elbow Evaluation (PRTEE) is the first questionnaire specifically designed for LE but in English. The aim of this study was to translate into Dutch and cross-culturally adapt the PRTEE and determine reliability and validity of the PRTEE-D (Dutch version). The PRTEE was cross-culturally adapted according to international guidelines. Participants (n = 122) were asked to fill out the PRTEE-D twice with a one week interval to assess test-retest reliability. Internal consistency of the PRTEE-D was determined by calculating Crohnbach's alphas for the questionnaire and subscales. Intraclass Correlation Coefficients (ICC) were calculated for the overall PRTEE-D score, pain and function subscale and individual questions to determine test-retest reliability. Additionally, the Disabilities for the Arm, Shoulder and Hand questionnaire (DASH) and Visual Analogue Scale (VAS) pain scores were obtained from 30 patients to assess construct validity; Spearman's correlation coefficients were calculated between the PRTEE-D (subscales) and DASH and VAS-pain scores. The PRTEE was successfully cross-culturally adapted into Dutch (PRTEE-D). Crohnbach's alpha for the first assessment of the PRTEE-D was 0.98; Crohnbach's alpha was 0.93 for the pain subscale and 0.97 for the function subscale. ICC for the PRTEE-D was 0.98; subscales also showed excellent ICC values (pain scale 0.97 and function scale 0.97). A significant moderate correlation exists between PRTEE-D and DASH (0.65) and PRTEE-D and VAS pain (0.68). The PRTEE was successfully cross-culturally adapted and this study showed that the PRTEE-D is reliable and valid to obtain an indication of severity of LE. An easy-to-use instrument for practitioners is now available and this facilitates comparing Dutch and international research data.

  12. Transcultural adaption and validation of the Spanish version of the Bipolar Depression Rating Scale (BDRS-S).

    Science.gov (United States)

    Sarró, Salvador; Madre, Mercè; Fernández-Corcuera, Paloma; Valentí, Marc; Goikolea, José M; Pomarol-Clotet, Edith; Berk, Michael; Amann, Benedikt L

    2015-02-01

    The Bipolar Depression Rating Scale (BDRS) arguably better captures symptoms in bipolar depression especially depressive mixed states than traditional unipolar depression rating scales. The psychometric properties of the Spanish adapted version, BDRS-S, are reported. The BDRS was translated into Spanish by two independent psychiatrists fluent in English and Spanish. After its back-translation into English, the BDRS-S was administered to 69 DSMI-IV bipolar I and II patients who were recruited from two Spanish psychiatric hospitals. The Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS) were concurrently administered. 42 patients were reviewed via video by four psychiatrists blind to the psychopathological status of those patients. In order to assess the BDRS-S intra-rater or test-retest validity, 22 subjects were assessed by the same investigator performing two evaluations within five days. The BDRS-S had a good internal consistency (Cronbach׳s α=0.870). We observed strong correlations between the BDRS-S and the HDRS (r=0.874) and MADRS (r=0.854) and also between the mixed symptom cluster score of the BDRS-S and the YMRS (r=0.803). Exploratory factor analysis revealed a three factor solution: psychological depressive symptoms cluster, somatic depressive symptoms cluster and mixed symptoms cluster. A relatively small sample size for a 20-item scale. The BDRS-S provides solid psychometric performance and in particular captures depressive or mixed symptoms in Spanish bipolar patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Left ventricular mechanics in humans with high aerobic fitness: adaptation independent of structural remodelling, arterial haemodynamics and heart rate

    Science.gov (United States)

    Stöhr, Eric J; McDonnell, Barry; Thompson, Jane; Stone, Keeron; Bull, Tom; Houston, Rory; Cockcroft, John; Shave, Rob

    2012-01-01

    Individuals with high aerobic fitness have lower systolic left ventricular strain, rotation and twist (‘left ventricular (LV) mechanics’) at rest, suggesting a beneficial reduction in LV myofibre stress and more efficient systolic function. However, the mechanisms responsible for this functional adaptation are not known and the influence of aerobic fitness on LV mechanics during dynamic exercise has never been studied. We assessed LV mechanics, LV wall thickness and dimensions, central augmentation index (AIx), aortic pulse wave velocity (aPWV), blood pressure and heart rate in 28 males (age: 21 ± 2 years SD) with a consistent physical activity level (no change >6 months). Individuals were examined at rest and during exercise (40% peak exercise capacity) and separated post hoc into a moderate and high aerobic fitness group (: 49 ± 5 and 63 ± 7 ml kg−1 min−1, respectively, P 0.05). However, for the same AIx, the high group had significantly lower LV apical rotation (P = 0.002) and LV twist (P = 0.003) while basal rotation and strain indices did not differ between groups (P > 0.05). We conclude that young males with high aerobic fitness have lower LV apical rotation at rest and during submaximal exercise that can occur without changes in gross LV structure, arterial haemodynamics or heart rate. The findings suggest a previously unknown type of physiological adaptation of the left ventricle that may have important implications for exercise training in older individuals and patient populations in which exercise training has previously failed to show clear benefits for LV function. PMID:22431336

  14. Content Adaptive Lagrange Multiplier Selection for Rate-Distortion Optimization in 3-D Wavelet-Based Scalable Video Coding

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2018-03-01

    Full Text Available Rate-distortion optimization (RDO plays an essential role in substantially enhancing the coding efficiency. Currently, rate-distortion optimized mode decision is widely used in scalable video coding (SVC. Among all the possible coding modes, it aims to select the one which has the best trade-off between bitrate and compression distortion. Specifically, this tradeoff is tuned through the choice of the Lagrange multiplier. Despite the prevalence of conventional method for Lagrange multiplier selection in hybrid video coding, the underlying formulation is not applicable to 3-D wavelet-based SVC where the explicit values of the quantization step are not available, with on consideration of the content features of input signal. In this paper, an efficient content adaptive Lagrange multiplier selection algorithm is proposed in the context of RDO for 3-D wavelet-based SVC targeting quality scalability. Our contributions are two-fold. First, we introduce a novel weighting method, which takes account of the mutual information, gradient per pixel, and texture homogeneity to measure the temporal subband characteristics after applying the motion-compensated temporal filtering (MCTF technique. Second, based on the proposed subband weighting factor model, we derive the optimal Lagrange multiplier. Experimental results demonstrate that the proposed algorithm enables more satisfactory video quality with negligible additional computational complexity.

  15. On the power and offset allocation for rate adaptation of spatial multiplexing in optical wireless MIMO channels

    KAUST Repository

    Park, Kihong

    2013-04-01

    In this paper, we consider resource allocation method in the visible light communication. It is challenging to achieve high data rate due to the limited bandwidth of the optical sources. In order to increase the spectral efficiency, we design a suitable multiple-input multiple-output (MIMO) system utilizing spatial multiplexing based on singular value decomposition and adaptive modulation. More specifically, after explaining why the conventional allocation method in radio frequency MIMO channels cannot be applied directly to the optical intensity channels, we theoretically derive a power allocation method for an arbitrary number of transmit and receive antennas for optical wireless MIMO systems. Based on three key constraints: the nonnegativity of the intensity-modulated signal, the aggregate optical power budget, and the bit error rate requirement, we propose a novel method to allocate the optical power, the offset value, and the modulation size. Based on some selected simulation results, we show that our proposed allocation method gives a better spectral efficiency at the expense of an increased computational complexity in comparison to a simple method that allocates the optical power equally among all the data streams. © 2013 IEEE.

  16. On the power and offset allocation for rate adaptation of spatial multiplexing in optical wireless MIMO channels

    KAUST Repository

    Park, Kihong; Ko, Youngchai; Alouini, Mohamed-Slim

    2013-01-01

    In this paper, we consider resource allocation method in the visible light communication. It is challenging to achieve high data rate due to the limited bandwidth of the optical sources. In order to increase the spectral efficiency, we design a suitable multiple-input multiple-output (MIMO) system utilizing spatial multiplexing based on singular value decomposition and adaptive modulation. More specifically, after explaining why the conventional allocation method in radio frequency MIMO channels cannot be applied directly to the optical intensity channels, we theoretically derive a power allocation method for an arbitrary number of transmit and receive antennas for optical wireless MIMO systems. Based on three key constraints: the nonnegativity of the intensity-modulated signal, the aggregate optical power budget, and the bit error rate requirement, we propose a novel method to allocate the optical power, the offset value, and the modulation size. Based on some selected simulation results, we show that our proposed allocation method gives a better spectral efficiency at the expense of an increased computational complexity in comparison to a simple method that allocates the optical power equally among all the data streams. © 2013 IEEE.

  17. Gait in ducks (Anas platyrhynchos and chickens (Gallus gallus – similarities in adaptation to high growth rate

    Directory of Open Access Journals (Sweden)

    B. M. Duggan

    2016-08-01

    Full Text Available Genetic selection for increased growth rate and muscle mass in broiler chickens has been accompanied by mobility issues and poor gait. There are concerns that the Pekin duck, which is on a similar selection trajectory (for production traits to the broiler chicken, may encounter gait problems in the future. In order to understand how gait has been altered by selection, the walking ability of divergent lines of high- and low-growth chickens and ducks was objectively measured using a pressure platform, which recorded various components of their gait. In both species, lines which had been selected for large breast muscle mass moved at a slower velocity and with a greater step width than their lighter conspecifics. These high-growth lines also spent more time supported by two feet in order to improve balance when compared with their lighter, low-growth conspecifics. We demonstrate that chicken and duck lines which have been subjected to intense selection for high growth rates and meat yields have adapted their gait in similar ways. A greater understanding of which components of gait have been altered in selected lines with impaired walking ability may lead to more effective breeding strategies to improve gait in poultry.

  18. 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.

  19. Adaptive mutations enhance assembly and cell-to-cell transmission of a high-titer hepatitis C virus genotype 5a Core-NS2 JFH1-based recombinant

    DEFF Research Database (Denmark)

    Mathiesen, Christian K; Prentoe, Jannick; Meredith, Luke W

    2015-01-01

    UNLABELLED: Recombinant hepatitis C virus (HCV) clones propagated in human hepatoma cell cultures yield relatively low infectivity titers. Here, we adapted the JFH1-based Core-NS2 recombinant SA13/JFH1C3405G,A3696G (termed SA13/JFH1orig), of the poorly characterized genotype 5a, to Huh7.5 cells......-titer production of diverse HCV strains would be advantageous. Our study offers important functional data on how cell culture-adaptive mutations identified in genotype 5a JFH1-based HCVcc permit high-titer culture by affecting HCV genesis through increasing virus assembly and HCV fitness by enhancing the virus...... specific infectivity and cell-to-cell transmission ability, without influencing the biophysical particle properties. High-titer HCVcc like the one described in this study may be pivotal in future vaccine-related studies where large quantities of infectious HCV particles are necessary....

  20. 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...

  1. Programming adaptive control to evolve increased metabolite production.

    Science.gov (United States)

    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.

  2. 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

  3. Optimal Policy of Cross-Layer Design for Channel Access and Transmission Rate Adaptation in Cognitive Radio Networks

    Science.gov (United States)

    He, Hao; Wang, Jun; Zhu, Jiang; Li, Shaoqian

    2010-12-01

    In this paper, we investigate the cross-layer design of joint channel access and transmission rate adaptation in CR networks with multiple channels for both centralized and decentralized cases. Our target is to maximize the throughput of CR network under transmission power constraint by taking spectrum sensing errors into account. In centralized case, this problem is formulated as a special constrained Markov decision process (CMDP), which can be solved by standard linear programming (LP) method. As the complexity of finding the optimal policy by LP increases exponentially with the size of action space and state space, we further apply action set reduction and state aggregation to reduce the complexity without loss of optimality. Meanwhile, for the convenience of implementation, we also consider the pure policy design and analyze the corresponding characteristics. In decentralized case, where only local information is available and there is no coordination among the CR users, we prove the existence of the constrained Nash equilibrium and obtain the optimal decentralized policy. Finally, in the case that the traffic load parameters of the licensed users are unknown for the CR users, we propose two methods to estimate the parameters for two different cases. Numerical results validate the theoretic analysis.

  4. Implementasi Jaringan Syaraf Tiruan Recurrent Menggunakan Gradient Descent Adaptive Learning Rate and Momentum Untuk Pendugaan Curah Hujan

    Directory of Open Access Journals (Sweden)

    Afan Galih Salman

    2011-06-01

    Full Text Available The artificial neural network (ANN technology in rainfall prediction can be done using the learning approach. The ANN prediction accuracy is measured by the determination coefficient (R2 and root mean square error (RMSE. This research implements Elman’s Recurrent ANN which is heuristically optimized based on el-nino southern oscilation (ENSO variables: wind, southern oscillation index (SOI, sea surface temperatur (SST dan outgoing long wave radiation (OLR to forecast regional monthly rainfall in Bongan Bali. The heuristic learning optimization done is basically a performance development of standard gradient descent learning algorithm into training algorithms: gradient descent momentum and adaptive learning rate. The patterns of input data affect the performance of Recurrent Elman neural network in estimation process. The first data group that is 75% training data and 25% testing data produce the maximum R2 leap 74,6% while the second data group that is 50% training data and 50% testing data produce the maximum R2 leap 49,8%.

  5. Optimal Policy of Cross-Layer Design for Channel Access and Transmission Rate Adaptation in Cognitive Radio Networks

    Directory of Open Access Journals (Sweden)

    Jiang Zhu

    2010-01-01

    Full Text Available In this paper, we investigate the cross-layer design of joint channel access and transmission rate adaptation in CR networks with multiple channels for both centralized and decentralized cases. Our target is to maximize the throughput of CR network under transmission power constraint by taking spectrum sensing errors into account. In centralized case, this problem is formulated as a special constrained Markov decision process (CMDP, which can be solved by standard linear programming (LP method. As the complexity of finding the optimal policy by LP increases exponentially with the size of action space and state space, we further apply action set reduction and state aggregation to reduce the complexity without loss of optimality. Meanwhile, for the convenience of implementation, we also consider the pure policy design and analyze the corresponding characteristics. In decentralized case, where only local information is available and there is no coordination among the CR users, we prove the existence of the constrained Nash equilibrium and obtain the optimal decentralized policy. Finally, in the case that the traffic load parameters of the licensed users are unknown for the CR users, we propose two methods to estimate the parameters for two different cases. Numerical results validate the theoretic analysis.

  6. NEAR-INFRARED ADAPTIVE OPTICS IMAGING OF INFRARED LUMINOUS GALAXIES: THE BRIGHTEST CLUSTER MAGNITUDE-STAR FORMATION RATE RELATION

    International Nuclear Information System (INIS)

    Randriamanakoto, Z.; Väisänen, P.; Escala, A.; Kankare, E.; Kotilainen, J.; Mattila, S.; Ryder, S.

    2013-01-01

    We have established a relation between the brightest super star cluster (SSC) magnitude in a galaxy and the host star formation rate (SFR) for the first time in the near-infrared (NIR). The data come from a statistical sample of ∼40 luminous IR galaxies (LIRGs) and starbursts utilizing K-band adaptive optics imaging. While expanding the observed relation to longer wavelengths, less affected by extinction effects, it also pushes to higher SFRs. The relation we find, M K ∼ –2.6log SFR, is similar to that derived previously in the optical and at lower SFRs. It does not, however, fit the optical relation with a single optical to NIR color conversion, suggesting systematic extinction and/or age effects. While the relation is broadly consistent with a size-of-sample explanation, we argue physical reasons for the relation are likely as well. In particular, the scatter in the relation is smaller than expected from pure random sampling strongly suggesting physical constraints. We also derive a quantifiable relation tying together cluster-internal effects and host SFR properties to possibly explain the observed brightest SSC magnitude versus SFR dependency

  7. Power allocation and achievable data rate in spectrum-sharing channels under adaptive primary service outage constraints

    KAUST Repository

    Yang, Yuli

    2012-09-01

    In this paper, we focus on a cognitive radio network where adaptive modulation is adopted in primary links. The gap between the primary user (PU)\\'s received signal-to-noise ratio (SNR) and the lower SNR boundary of the modulation mode that is being used, provides an interference-tolerable zone. Based on this gap, a secondary user (SU) has an increased opportunity to access the licensed spectrum and to determine the transmit power it should use to keep the PU\\'s quality-of-service (QoS) unaffected. However, since the SU cannot obtain perfect information on the PU\\'s received SNR, it has to choose an SNR point between the lower and upper boundaries of the PU\\'s current modulation mode as if this point were the real SNR received by the PU. Considering this issue, in order to quantify the effect of the SU\\'s transmissions on the PU\\'s QoS, we define the PU\\'s service outage probability and obtain its closed-form expressions by taking into account whether the peak transmit power constraint is imposed on the secondary\\'s transmission or not. Subsequently, we derive the SU\\'s achievable data rate in closed form for counterpart scenarios. Numerical results provided here quantify the relation between the PU\\'s service outage probability and the SU\\'s achievable data rate, which further demonstrate that the higher the peak transmit power a secondary transmitter can support, the better performance the cognitive radio network can achieve. © 2012 IEEE.

  8. Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes.

    Science.gov (United States)

    Souza, C J H; McNeilly, A S; Benavides, M V; Melo, E O; Moraes, J C F

    2014-10-01

    Litter size (LS) in sheep is determined mainly by ovulation rate (OR). Several polymorphisms have been identified in the growth differentiation factor 9 (GDF9) gene that result in an increase in OR and prolificacy of sheep. Screening the databank of the Brazilian Sheep Breeders Association for triplet delivery, we identified flocks of prolific Ile de France ewes. After resequencing of GDF9, a point mutation (c.943C>T) was identified, resulting in a non-conservative amino acid change (p.Arg315Cys) in the cleavage site of the propeptide. This new allele was called Vacaria (FecG(v) ). A flock of half-sib ewes was evaluated for OR in the first three breeding seasons, and Vacaria heterozygotes had higher OR (P develop up to small antral stages, although with abnormal oocyte morphology and altered arrangement of granulosa cells. After the collapse of the oocyte in most follicles, the remaining cells formed clusters that persisted in the ovary. This SNP is useful to improve selection for dam prolificacy and also as a model to investigate GDF9 post-translation processing and the fate of the follicular cells that remain after the oocyte demise. © 2014 Stichting International Foundation for Animal Genetics.

  9. Evaluation of discriminating power of 13 Y chromosome markers with high rate of mutation (RM Y-STR) in the Costa Rican population

    International Nuclear Information System (INIS)

    Solano Matamoros, Carlos

    2014-01-01

    The Y chromosome microsatellites analysis has had among its purposes the obtaining of a male haplotype from mixtures with high prevalence of female genetic material, such as sexual offenses. The currently available markers set as AmpFISTR® Yfiler® have offered haplotype resolution to level of incomplete patrilineal line. This limitation has been particularly important when is needed to supplement paternity studies. The implementation expected of the 13 Y chromosome microsatellites with high mutation rate (RM Y-STR) recently described, has improved the discriminating power of microsatellite analysis of Y in the forensic context. However, for implemetation it has been necessary to obtain the frequencies of haplotypes in the Costa Rican population. In addition, the discriminating power of the new markers is evaluated and compared with current markers set, such as AmpFISTR® Yfile®, to determine whether the former have an advantage over the latter. The use of a powerful new tool has been claimed for a more efficient and effective application of justice in Costa Rica, specially in sexual offenses [es

  10. Use of Adaptive Laboratory Evolution To Discover Key Mutations Enabling Rapid Growth of Escherichia coli K-12 MG1655 on Glucose Minimal Medium

    DEFF Research Database (Denmark)

    LaCroix, Ryan A.; Sandberg, Troy E.; O'Brien, Edward J.

    2015-01-01

    Adaptive laboratory evolution (ALE) has emerged as an effective tool for scientific discovery and addressing biotechnological needs. Much of ALE's utility is derived from reproducibly obtained fitness increases. Identifying causal genetic changes and their combinatorial effects is challenging...

  11. Morphological adaptation of rumen papillae during the dry period and early lactation as affected by rate of increase of concentrate allowance

    NARCIS (Netherlands)

    Dieho, K.|info:eu-repo/dai/nl/314000550; Bannink, A.; Geurts, I. A L; Schonewille, J. T.|info:eu-repo/dai/nl/185364306; Gort, G.; Dijkstra, J.

    2016-01-01

    Knowledge of the morphological adaptation of rumen papilla, which plays an important role in volatile fatty acid absorption, in dry and early lactation dairy cattle is limited. Therefore, macro- and microscopic changes in papilla morphology during the dry period and lactation and the effect of rate

  12. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

    Science.gov (United States)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  13. Metabolic engineering of an ATP-neutral Embden-Meyerhof-Parnas pathway in Corynebacterium glutamicum: growth restoration by an adaptive point mutation in NADH dehydrogenase.

    Science.gov (United States)

    Komati Reddy, Gajendar; Lindner, Steffen N; Wendisch, Volker F

    2015-03-01

    Corynebacterium glutamicum uses the Embden-Meyerhof-Parnas pathway of glycolysis and gains 2 mol of ATP per mol of glucose by substrate-level phosphorylation (SLP). To engineer glycolysis without net ATP formation by SLP, endogenous phosphorylating NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was replaced by nonphosphorylating NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GapN) from Clostridium acetobutylicum, which irreversibly converts glyceraldehyde-3-phosphate (GAP) to 3-phosphoglycerate (3-PG) without generating ATP. As shown recently (S. Takeno, R. Murata, R. Kobayashi, S. Mitsuhashi, and M. Ikeda, Appl Environ Microbiol 76:7154-7160, 2010, http://dx.doi.org/10.1128/AEM.01464-10), this ATP-neutral, NADPH-generating glycolytic pathway did not allow for the growth of Corynebacterium glutamicum with glucose as the sole carbon source unless hitherto unknown suppressor mutations occurred; however, these mutations were not disclosed. In the present study, a suppressor mutation was identified, and it was shown that heterologous expression of udhA encoding soluble transhydrogenase from Escherichia coli partly restored growth, suggesting that growth was inhibited by NADPH accumulation. Moreover, genome sequence analysis of second-site suppressor mutants that were able to grow faster with glucose revealed a single point mutation in the gene of non-proton-pumping NADH:ubiquinone oxidoreductase (NDH-II) leading to the amino acid change D213G, which was shared by these suppressor mutants. Since related NDH-II enzymes accepting NADPH as the substrate possess asparagine or glutamine residues at this position, D213G, D213N, and D213Q variants of C. glutamicum NDH-II were constructed and were shown to oxidize NADPH in addition to NADH. Taking these findings together, ATP-neutral glycolysis by the replacement of endogenous NAD-dependent GAPDH with NADP-dependent GapN became possible via oxidation of NADPH formed in this pathway by mutant NADPH

  14. 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

  15. Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs

    DEFF Research Database (Denmark)

    Hickman, Rachel A.; Munck, Christian; Sommer, Morten Otto Alexander

    2017-01-01

    + CHL and CHL + CIP). We find that lineages evolved to antibiotic combinations exhibit different resistance allele dynamics compared with those of single-drug evolved lineages, especially for a drug pair with reciprocal collateral sensitivity. During adaptation, we observed interfering, superimposing...

  16. Hypervariable region 1 deletion and required adaptive envelope mutations confer decreased dependency on scavenger receptor class B type I and low-density lipoprotein receptor for hepatitis C virus

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Serre, Stéphanie B N; Ramirez, Santseharay

    2014-01-01

    -deleted viruses. Apolipoprotein E (ApoE)-specific HCV neutralization was similar for H77, J6, and S52 viruses with and without HVR1. In conclusion, HVR1 and HVR1-related adaptive envelope mutations appeared to be involved in LDLr and SR-BI dependency, respectively. Also, LDLr served Apo....../S733F), S52(ΔHVR1/A369V), and S52(A369V), but not for J6(ΔHVR1). Low-density lipoprotein receptor (LDLr) dependency was decreased for HVR1-deleted viruses, but not for H77(N476D/S733F) and S52(A369V). Soluble LDLr neutralization revealed strong inhibition of parental HCV but limited effect against HVR1...

  17. Microanatomical and histological features in the long bones of Mosasaurine mosasaurs (Reptilia, Squamata)--implications for aquatic adaptation and growth rates.

    Science.gov (United States)

    Houssaye, Alexandra; Lindgren, Johan; Pellegrini, Rodrigo; Lee, Andrew H; Germain, Damien; Polcyn, Michael J

    2013-01-01

    During their evolution in the Late Cretaceous, mosasauroids attained a worldwide distribution, accompanied by a marked increase in body size and open ocean adaptations. This transition from land-dwellers to highly marine-adapted forms is readily apparent not only at the gross anatomic level but also in their inner bone architecture, which underwent profound modifications. The present contribution describes, both qualitatively and quantitatively, the internal organization (microanatomy) and tissue types and characteristics (histology) of propodial and epipodial bones in one lineage of mosasauroids; i.e., the subfamily Mosasaurinae. By using microanatomical and histological data from limb bones in combination with recently acquired knowledge on the inner structure of ribs and vertebrae, and through comparisons with extant squamates and semi-aquatic to fully marine amniotes, we infer possible implications on mosasaurine evolution, aquatic adaptation, growth rates, and basal metabolic rates. Notably, we observe the occurrence of an unusual type of parallel-fibered bone, with large and randomly shaped osteocyte lacunae (otherwise typical of fibrous bone) and particular microanatomical features in Dallasaurus, which displays, rather than a spongious inner organization, bone mass increase in its humeri and a tubular organization in its femora and ribs. The dominance of an unusual type of parallel-fibered bone suggests growth rates and, by extension, basal metabolic rates intermediate between that of the extant leatherback turtle, Dermochelys, and those suggested for plesiosaur and ichthyosaur reptiles. Moreover, the microanatomical features of the relatively primitive genus Dallasaurus differ from those of more derived mosasaurines, indicating an intermediate stage of adaptation for a marine existence. The more complete image of the various microanatomical trends observed in mosasaurine skeletal elements supports the evolutionary convergence between this lineage of

  18. Microanatomical and histological features in the long bones of Mosasaurine mosasaurs (Reptilia, Squamata--implications for aquatic adaptation and growth rates.

    Directory of Open Access Journals (Sweden)

    Alexandra Houssaye

    Full Text Available BACKGROUND: During their evolution in the Late Cretaceous, mosasauroids attained a worldwide distribution, accompanied by a marked increase in body size and open ocean adaptations. This transition from land-dwellers to highly marine-adapted forms is readily apparent not only at the gross anatomic level but also in their inner bone architecture, which underwent profound modifications. METHODOLOGY/PRINCIPAL FINDINGS: The present contribution describes, both qualitatively and quantitatively, the internal organization (microanatomy and tissue types and characteristics (histology of propodial and epipodial bones in one lineage of mosasauroids; i.e., the subfamily Mosasaurinae. By using microanatomical and histological data from limb bones in combination with recently acquired knowledge on the inner structure of ribs and vertebrae, and through comparisons with extant squamates and semi-aquatic to fully marine amniotes, we infer possible implications on mosasaurine evolution, aquatic adaptation, growth rates, and basal metabolic rates. Notably, we observe the occurrence of an unusual type of parallel-fibered bone, with large and randomly shaped osteocyte lacunae (otherwise typical of fibrous bone and particular microanatomical features in Dallasaurus, which displays, rather than a spongious inner organization, bone mass increase in its humeri and a tubular organization in its femora and ribs. CONCLUSIONS/SIGNIFICANCE: The dominance of an unusual type of parallel-fibered bone suggests growth rates and, by extension, basal metabolic rates intermediate between that of the extant leatherback turtle, Dermochelys, and those suggested for plesiosaur and ichthyosaur reptiles. Moreover, the microanatomical features of the relatively primitive genus Dallasaurus differ from those of more derived mosasaurines, indicating an intermediate stage of adaptation for a marine existence. The more complete image of the various microanatomical trends observed in mosasaurine

  19. Doubling the referral rate of monogenic diabetes through a nationwide information campaign--update on glucokinase gene mutations in a Polish cohort.

    Science.gov (United States)

    Borowiec, M; Fendler, W; Antosik, K; Baranowska, A; Gnys, P; Zmyslowska, A; Malecki, M; Mlynarski, W

    2012-12-01

    In order to improve recruitment efficiency of patients with monogenic diabetes in Poland, in September 2010 a nationwide advertising campaign was launched to inform multiple target groups interested or participating in pediatric diabetologic care. Promotional actions aimed at informing physicians, patients, parents and educators were carried out through nationwide newspapers, medical and patient-developed websites and educational conference presentations. Recruitment efficiency was compared between September 2010 (publication of the first report on project's results) and the following 12 months. The number of families and patients referred to genetic screening was increased by 92% and 96% respectively nearly reaching the numbers recruited throughout the initial 4 years of the project. Participation of non-academic centers was also significantly increased from 2.3% to 7.5% (p = 0.0005). DNA sequencing and Multiplex Ligation-dependant Probe Amplification of the glucokinase gene resulted in finding 50 different mutations. Among those mutations, 19 were novel variants, which included: 17 missense mutations (predicted to be pathogenic according to bioinformatic analysis), 1 nonsense mutation and 1 mutation affecting a consensus intronic splice site. Advertising actions directed at increasing recruitment efficiency are a powerful and possibly neglected tool in screening for rare genetic disorders with a clinically defined phenotype. © 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  20. Using combined measurements for comparison of light induction of stomatal conductance, electron transport rate and CO2 fixation in woody and fern species adapted to different light regimes.

    Science.gov (United States)

    Wong, Shau-Lian; Chen, Chung-Wei; Huang, Hsien-Wen; Weng, Jen-Hsien

    2012-05-01

    We aimed to understand the relation of photosynthetic rate (A) with g(s) and electron transport rate (ETR) in species of great taxonomic range and light adaptation capability during photosynthetic light induction. We studied three woody species (Alnus formosana, Ardisia crenata and Ardisia cornudentata) and four fern species (Pyrrosia lingus, Asplenium antiquum, Diplazium donianum and Archangiopteris somai) with different light adaptation capabilities. Pot-grown materials received 100 and/or 10% sunlight according to their light adaptation capabilities. At least 4 months after light acclimation, CO(2) and H(2)O exchange and chlorophyll fluorescence were measured simultaneously by equipment in the laboratory. In plants adapted or acclimated to low light, dark-adapted leaves exposed to 500 or 2000 µmol m(-2) s(-1) photosynthetic photon flux (PPF) for 30 min showed low gross photosynthetic rate (P(g)) and short time required to reach 90% of maximum P(g) (). At the initiation of illumination, two broad-leaved understory shrubs and the four ferns, especially ferns adapted to heavy shade, showed higher stomatal conductance (g(s)) than pioneer tree species; materials with higher g(s) had short at both 500 and 2000 µmol m(-2) s(-1) PPF. With 500 or 2000 µmol m(-2) s(-1) PPF, the g(s) for the three woody species increased from 2 to 30 min after the start of illumination, but little change in the g(s) of the four ferns. Thus, P(g) and g(s) were not correlated for all material measured at the same PPF and induction time. However, P(g) was positively correlated with ETR, even though CO(2) assimilation may be influenced by stomatal, biochemical and photoinhibitory limitations. In addition, was closely related to time required to reach 90% maximal ETR for all materials and with two levels of PPF combined. Thus, ETR is a good indicator for estimating the light induction of photosynthetic rate of species, across a wide taxonomic range and light adaptation and acclimation

  1. Vacuolar Protein Sorting genes in Parkinson’s Disease: a re-appraisal of mutations detection rate and neurobiology of disease

    Directory of Open Access Journals (Sweden)

    Stefano Gambardella

    2016-11-01

    Full Text Available Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN. Recently, retromers have been linked to Parkinson's Disease (PD since the identification of the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35 as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation, which represent critical steps in the molecular mechanisms of disease. Other slightly penetrant and mildly deleterious mutations in VPS genes have been reported in both sporadic and familial PD. Therefore, understanding the actual prevalence of the whole range of VPS gene mutations is key to understand the relevance of retromers impairment in PD. This scenario indicates a plethora of mutations occurring in different pathways (autophagy, mitophagy, proteasome, endosomes, protein misfolding all converging to cell clearing systems. This may explain how genetic predispositions to PD may derive from slightly deleterious mutations when combining with heterogeneous environmental factors. This manuscript is a re-appraisal of genetic data produced in the last five years redefining the prevalence of VPS mutations in PD. The prevalence of p.Asp620Asn in VPS35 is 0.286 of familial PD. This data increases up to 0.548 considering mutations affecting all VPS genes, thus representing the second most frequent autosomal dominant PD genotype. This high prevalence, joined with increased awareness of the key role of retromers alterations in PD, strongly candidate environmentally-induced VPS alterations as key molecular mechanisms in the genesis of PD. rations as key molecular mechanisms in the genesis of PD.

  2. Adaptive support ventilation may deliver unwanted respiratory rate-tidal volume combinations in patients with acute lung injury ventilated according to an open lung concept.

    Science.gov (United States)

    Dongelmans, Dave A; Paulus, Frederique; Veelo, Denise P; Binnekade, Jan M; Vroom, Margreeth B; Schultz, Marcus J

    2011-05-01

    With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury. Patients with acute lung injury were ventilated according to a local guideline advising the use of lower V(T) (6-8 ml/kg predicted body weight), high concentrations of positive end-expiratory pressure, and recruitment maneuvers. Ventilation parameters were recorded when the ventilator was switched to adaptive support ventilation, and after recruitment maneuvers. If V(T) increased more than 8 ml/kg predicted body weight, airway pressure was limited to correct for the rise of V(T). Ten patients with a mean (±SD) Pao(2)/Fio(2) of 171 ± 86 mmHg were included. After a switch from pressure-controlled ventilation to adaptive support ventilation, respiratory rate declined (from 31 ± 5 to 21 ± 6 breaths/min; difference = 10 breaths/min, 95% CI 3-17 breaths/min, P = 0.008) and V(T) increased (from 6.5 ± 0.8 to 9.0 ± 1.6 ml/kg predicted body weight; difference = 2.5 ml, 95% CI 0.4-4.6 ml/kg predicted body weight, P = 0.02). Pressure limitation corrected for the rise of V(T), but minute ventilation declined, forcing the user to switch back to pressure-controlled ventilation. Adaptive support ventilation, compared with pressure-controlled ventilation in an open lung strategy setting, delivers a lower respiratory rate-higher V(T) combination. Pressure limitation does correct for the rise of V(T), but leads to a decline in minute ventilation.

  3. Evolutionary rescue and local adaptation under different rates of temperature increase: a combined analysis of changes in phenotype expression and genotype frequency in Paramecium microcosms.

    Science.gov (United States)

    Killeen, Joshua; Gougat-Barbera, Claire; Krenek, Sascha; Kaltz, Oliver

    2017-04-01

    Evolutionary rescue (ER) occurs when populations, which have declined due to rapid environmental change, recover through genetic adaptation. The success of this process and the evolutionary trajectory of the population strongly depend on the rate of environmental change. Here we investigated how different rates of temperature increase (from 23 to 32 °C) affect population persistence and evolutionary change in experimental microcosms of the protozoan Paramecium caudatum. Consistent with theory on ER, we found that those populations experiencing the slowest rate of temperature increase were the least likely to become extinct and tended to be the best adapted to the new temperature environment. All high-temperature populations were more tolerant to severe heat stress (35, 37 °C), indicating a common mechanism of heat protection. High-temperature populations also had superior growth rates at optimum temperatures, leading to the absence of a pattern of local adaptation to control (23 °C) and high-temperature (32 °C) environments. However, high-temperature populations had reduced growth at low temperatures (5-9 °C), causing a shift in the temperature niche. In part, the observed evolutionary change can be explained by selection from standing variation. Using mitochondrial markers, we found complete divergence between control and high-temperature populations in the frequencies of six initial founder genotypes. Our results confirm basic predictions of ER and illustrate how adaptation to an extreme local environment can produce positive as well as negative correlated responses to selection over the entire range of the ecological niche. © 2017 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-07-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.

  6. A loss-of-function mutation in the PAS kinase Rim15p is related to defective quiescence entry and high fermentation rates of Saccharomyces cerevisiae sake yeast strains.

    Science.gov (United States)

    Watanabe, Daisuke; Araki, Yuya; Zhou, Yan; Maeya, Naoki; Akao, Takeshi; Shimoi, Hitoshi

    2012-06-01

    Sake yeast cells have defective entry into the quiescent state, allowing them to sustain high fermentation rates. To reveal the underlying mechanism, we investigated the PAS kinase Rim15p, which orchestrates initiation of the quiescence program in Saccharomyces cerevisiae. We found that Rim15p is truncated at the carboxyl terminus in modern sake yeast strains as a result of a frameshift mutation. Introduction of this mutation or deletion of the full-length RIM15 gene in a laboratory strain led to a defective stress response, decreased synthesis of the storage carbohydrates trehalose and glycogen, and impaired G(1) arrest, which together closely resemble the characteristic phenotypes of sake yeast. Notably, expression of a functional RIM15 gene in a modern sake strain suppressed all of these phenotypes, demonstrating that dysfunction of Rim15p prevents sake yeast cells from entering quiescence. Moreover, loss of Rim15p or its downstream targets Igo1p and Igo2p remarkably improved the fermentation rate in a laboratory strain. This finding verified that Rim15p-mediated entry into quiescence plays pivotal roles in the inhibition of ethanol fermentation. Taken together, our results suggest that the loss-of-function mutation in the RIM15 gene may be the key genetic determinant of the increased ethanol production rates in modern sake yeast strains.

  7. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  8. Controlling the chaotic discrete-Hénon system using a feedforward neural network with an adaptive learning rate

    OpenAIRE

    GÖKCE, Kürşad; UYAROĞLU, Yılmaz

    2013-01-01

    This paper proposes a feedforward neural network-based control scheme to control the chaotic trajectories of a discrete-Hénon map in order to stay within an acceptable distance from the stable fixed point. An adaptive learning back propagation algorithm with online training is employed to improve the effectiveness of the proposed method. The simulation study carried in the discrete-Hénon system verifies the validity of the proposed control system.

  9. Maximum inflation of the type 1 error rate when sample size and allocation rate are adapted in a pre-planned interim look.

    Science.gov (United States)

    Graf, Alexandra C; Bauer, Peter

    2011-06-30

    We calculate the maximum type 1 error rate of the pre-planned conventional fixed sample size test for comparing the means of independent normal distributions (with common known variance) which can be yielded when sample size and allocation rate to the treatment arms can be modified in an interim analysis. Thereby it is assumed that the experimenter fully exploits knowledge of the unblinded interim estimates of the treatment effects in order to maximize the conditional type 1 error rate. The 'worst-case' strategies require knowledge of the unknown common treatment effect under the null hypothesis. Although this is a rather hypothetical scenario it may be approached in practice when using a standard control treatment for which precise estimates are available from historical data. The maximum inflation of the type 1 error rate is substantially larger than derived by Proschan and Hunsberger (Biometrics 1995; 51:1315-1324) for design modifications applying balanced samples before and after the interim analysis. Corresponding upper limits for the maximum type 1 error rate are calculated for a number of situations arising from practical considerations (e.g. restricting the maximum sample size, not allowing sample size to decrease, allowing only increase in the sample size in the experimental treatment). The application is discussed for a motivating example. Copyright © 2011 John Wiley & Sons, Ltd.

  10. RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

    Science.gov (United States)

    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

  11. Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination

    International Nuclear Information System (INIS)

    Ohara, Maki; Funyu, Yumi; Ebara, Shunsuke

    2014-01-01

    Ionizing radiation induces DNA double-strand breaks (DSBs). Mammalian cells repair DSBs through multiple pathways, and the repair pathway that is utilized may affect cellular radiation sensitivity. In this study, we examined effects on cellular radiosensitivity resulting from functional alterations in homologous recombination (HR). HR was inhibited by overexpression of the forkhead-associated (FHA) domain-mutated NBS1 (G27D/R28D: FHA-2D) protein in HeLa cells or in hamster cells carrying a human X-chromosome. Cells expressing FHA-2D presented partially (but significantly) HR-deficient phenotypes, which were assayed by the reduction of gene conversion frequencies measured with a reporter assay, a decrease in radiation-induced Mre11 foci formation, and hypersensitivity to camptothecin treatments. Interestingly, ectopic expression of FHA-2D did not increase the frequency of radiation-induced somatic mutations at the HPRT locus, suggesting that a partial reduction of HR efficiency has only a slight effect on genomic stability. The expression of FHA-2D rendered the exponentially growing cell population slightly (but significantly) more sensitive to ionizing radiation. This radiosensitization effect due to the expression of FHA-2D was enhanced when the cells were irradiated with split doses delivered at 24-h intervals. Furthermore, enhancement of radiation sensitivity by split dose irradiation was not seen in contact-inhibited G0/G1 populations, even though the cells expressed FHA-2D. These results suggest that the FHA domain of NBS1 might be an effective molecular target that can be used to induce radiosensitization using low molecular weight chemicals, and that partial inhibition of HR might improve the effectiveness of cancer radiotherapy. (author)

  12. Translation, Cross-Cultural Adaptation, and Validation of the Activity Rating Scale for Disorders of the Knee

    DEFF Research Database (Denmark)

    Flosadottir, Vala; Roos, Ewa M; Ageberg, Eva

    2017-01-01

    and cross-culturally adapt the ARS into Swedish and to assess measurement properties of the Swedish version of the ARS. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The COSMIN guidelines were followed. Participants (N = 100 [55 women]; mean age, 27 years) who were undergoing...... rehabilitation for a knee injury completed the ARS twice for test-retest reliability. The Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale (TAS), and modernized Saltin-Grimby Physical Activity Level Scale (SGPALS) were administered at baseline to validate the ARS. Construct validity...

  13. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

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

    Science.gov (United States)

    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.

  15. Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

    International Nuclear Information System (INIS)

    Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

    2008-01-01

    Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

  16. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression

    International Nuclear Information System (INIS)

    Toledo, S.M. de; Mitchel, R.E.J.; Azzam, E.; Ottawa Univ., ON; Raaphorst, G.P.

    1994-01-01

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs

  17. Individual adaptation to experimental changes in running speed and step rate during treadmill running in injury-free runners

    DEFF Research Database (Denmark)

    Larsen, Lars Henrik; Kjeldsen, Nikolaj Hørby; Stoklund Pedersen, Daniel

    % velocity with self-selected and 105% step rate and 100% velocity with 105% step rate) and 2 sides (left and right) were analyzed by RM- ANOVA with a Greenhouse-Geisser correction and significance level 0.05 in IBM SPSS version 22.0 Results A 2-way RM-ANOVA including sides (left and right) and conditions (5...

  18. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

  19. Somatic mutation in peripheral blood lymphocytes among Metro Manila residents: indicator of exposure to environmental pollution

    International Nuclear Information System (INIS)

    Yulo-Nazarea, M.T.; Cobar, M.L.C.; Endriga, M.A.; Sta Maria, E.J.; Nato, A.Q.; Eduardo, J.; Dy, R.

    1994-01-01

    Metro Manila is ranked as one of the world's most polluted cities where air quality levels are 2-3 times higher than the levels set by WHO. Development of diseases could be alleviated if early warning signs as occurrence of gene mutations are detected early enough. The adapted hypoxanthine guanine phosphoribosyl transferase (HGPRT) mutation assay measures the degree of mutation on the HGPRT gene and allows rapid evaluation of the occurrence of mutation in an individual exposed to radiation or mutagens within six months after exposure. The objective of the project is to (1) assay exposure of Metro Manila residents exposed to environmental pollution, (2) determine population groups significantly affected by pollutants and (3) construct an environmental baseline HGPRT mutation data bank specific to area in Metro Manila. A composite table of personal information of donors against mutation index in two barangays in Venezuela is presented. About 30% of the total samples are shown to have mutation index greater than 0.5. So far, the data show a slightly higher mutation rate among donors who are smokers with more than 5 hours outdoor exposure to pollutants per day than the corresponding class of non-smokers. (author). 5 refs.; 5 tabs

  20. Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

    Science.gov (United States)

    2018-01-01

    Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired

  1. On the power and offset allocation for rate adaptation of spatial multiplexing in optical wireless MIMO channels

    KAUST Repository

    Park, Kihong; Ko, Youngchai; Alouini, Mohamed-Slim

    2011-01-01

    Visible light communication (VLC) using optical sources which can be simultaneously utilized for illumination and communication is currently an attractive option for wireless personal area network. Improving the data rate in optical wireless

  2. Executive Function and Adaptive Behavior in Muenke Syndrome.

    Science.gov (United States)

    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.

  3. The risk of extinction - the mutational meltdown or the overpopulation

    OpenAIRE

    Malarz, K.

    2006-01-01

    The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.

  4. The risk of extinction - the mutational meltdown or the overpopulation.

    Science.gov (United States)

    Malarz, Krzysztof

    2007-04-01

    The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.

  5. 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.

  6. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  7. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Radiation-induced mutation at minisatellite loci

    International Nuclear Information System (INIS)

    Dubrova, Y.E.; Nesterov, V.N.; Krouchinsky, N.G.

    1997-01-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of γ-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure 137 Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed

  10. 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)

  11. Cross-cultural adaptation and reliability and validity of the Dutch Patient-Rated Tennis Elbow Evaluation (PRTEE-D)

    NARCIS (Netherlands)

    van Ark, Mathijs; Zwerver, Johannes; Diercks, Ronald L; van den Akker-Scheek, Inge

    2014-01-01

    Background: Lateral Epicondylalgia (LE) is a common injury for which no reliable and valid measure exists to determine severity in the Dutch language. The Patient-Rated Tennis Elbow Evaluation (PRTEE) is the first questionnaire specifically designed for LE but in English. The aim of this study was

  12. Psychometric Adaptation of the Beck Hopelessness Scale as a Self-Rated Suicide Risk Screening Instrument Among Nigerian University Students.

    Science.gov (United States)

    Aloba, Olutayo; Awe, Oluwatosin; Adelola, Aderopo; Olatunji, Philemon; Aloba, Tolulope

    2018-03-01

    Globally, suicide is the most important cause of mortality among adolescents and young adults. The factor that correlates most significantly with suicide is hopelessness. The aim is to explore the psychometric adaptation of the Beck Hopelessness Scale (BHS) as a suicide risk evaluation tool among Nigerian university students. A total of 554 Nigerian students completed the BHS and the Depression Anxiety Stress Scale (DASS). Suicide risk level among them was determined by interviewing them with the Mini International Neuropsychiatric Interview Suicidality module. Cronbach's alpha for the 16-item BHS was 0.87. It exhibited satisfactory concurrent validity with the Mini International Neuropsychiatric Interview (MINI) Suicidality module and the subscales of the DASS among the students. The 2-factor model of the BHS-16 exhibited satisfactory indices of fitness (goodness of fit index = 0.930; parsimonious goodness of fit index = 0.601; comparative fit index = 0.934; incremental fit index = 0.936; Tucker-Lewis index = 0.910; root mean square error of approximation = 0.059; χ 2 / df = 1.9). Receiver operating characteristics curve indicated that the best cutoff score for those categorized as high suicide risk was 7 (sensitivity 0.700, specificity 0.908, AUC = 0.897). The BHS has satisfactory psychometric properties as a suicide risk screening tool among Nigerian university students.

  13. Power Spectral Analysis of Short-Term Heart Rate Variability in Healthy and Arrhythmia Subjects by the Adaptive Continuous Morlet Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Ram Sewak SINGH

    2017-12-01

    Full Text Available Power spectral analysis of short-term heart rate variability (HRV can provide instant valuable information to understand the functioning of autonomic control over the cardiovascular system. In this study, an adaptive continuous Morlet wavelet transform (ACMWT method has been used to describe the time-frequency characteristics of the HRV using band power spectra and the median value of interquartile range. Adaptation of the method was based on the measurement of maximum energy concentration. The ACMWT has been validated on synthetic signals (i.e. stationary, non-stationary as slow varying and fast changing frequency with time modeled as closest to dynamic changes in HRV signals. This method has been also tested in the presence of additive white Gaussian noise (AWGN to show its robustness towards the noise. From the results of testing on synthetic signals, the ACMWT was found to be an enhanced energy concentration estimator for assessment of power spectral of short-term HRV time series compared to adaptive Stockwell transform (AST, adaptive modified Stockwell transform (AMST, standard continuous Morlet wavelet transform (CMWT and Stockwell transform (ST estimators at statistical significance level of 5%. Further, the ACMWT was applied to real HRV data from Fantasia and MIT-BIH databases, grouped as healthy young group (HYG, healthy elderly group (HEG, arrhythmia controlled medication group (ARCMG, and supraventricular tachycardia group (SVTG subjects. The global results demonstrate that spectral indices of low frequency power (LFp and high frequency power (HFp of HRV were decreased in HEG compared to HYG subjects (p<0.0001. While LFp and HFp indices were increased in ARCMG compared to HEG (p<0.00001. The LFp and HFp components of HRV obtained from SVTG were reduced compared to other group subjects (p<0.00001.

  14. Adapting the Caesium-137 technique to document soil redistribution rates associated with traditional cultivation practices in Haiti.

    Science.gov (United States)

    Velasco, H; Astorga, R Torres; Joseph, D; Antoine, J S; Mabit, L; Toloza, A; Dercon, G; Walling, Des E

    2018-03-01

    Large-scale deforestation, intensive land use and unfavourable rainfall conditions are responsible for significant continuous degradation of the Haitian uplands. To develop soil conservation strategies, simple and cost-effective methods are needed to assess rates of soil loss from farmland in Haiti. The fallout radionuclide caesium-137 ( 137 Cs) provides one such means of documenting medium-term soil redistribution rates. In this contribution, the authors report the first use in Haiti of 137 Cs measurements to document soil redistribution rates and the associated pattern of erosion/sedimentation rates along typical hillslopes within a traditional upland Haitian farming area. The local 137 Cs reference inventory, measured at an adjacent undisturbed flat area, was 670 Bq m -2 (SD = 100 Bq m -2 , CV = 15%, n = 7). Within the study area, where cultivation commenced in 1992 after deforestation, three representative downslope transects were sampled. These were characterized by 137 Cs inventories ranging from 190 to 2200 Bq m -2 . Although, the study area was cultivated by the local farmers, the 137 Cs depth distributions obtained from the area differed markedly from those expected from a cultivated area. They showed little evidence of tillage mixing within the upper part of the soil or, more particularly, of the near-uniform activities normally associated with the plough layer or cultivation horizon. They were very similar to that found at the reference site and were characterized by high 137 Cs activities at the surface and much lower activities at greater depths. This situation is thought to reflect the traditional manual tillage practices which cause limited disturbance and mixing of the upper part of the soil. It precluded the use of the conversion models normally used to estimate soil redistribution rates from 137 Cs measurements on cultivated soils and the Diffusion and Migration conversion model frequently used for uncultivated soils was modified for

  15. On the power and offset allocation for rate adaptation of spatial multiplexing in optical wireless MIMO channels

    KAUST Repository

    Park, Kihong

    2011-07-01

    Visible light communication (VLC) using optical sources which can be simultaneously utilized for illumination and communication is currently an attractive option for wireless personal area network. Improving the data rate in optical wireless communication system is challenging due to the limited bandwidth of the optical sources. In this paper, we design the singular value decomposition (SVD)- based multiplexing multiple-input multiple-output (MIMO) system to support two data streams in optical wireless channels. Noting that the conventional allocation method in radio frequency (RF) MIMO channels cannot be applied directly to the optical intensity channels, we propose a novel method to allocate the optical power, the offset value and the modulation size for maximum sum rate under the constraints of the nonnegativity of the modulated signals, the aggregate optical power and the bit error rate (BER) requirement. The simulation results show that the proposed allocation method gives the better performance than the method to allocate the optical power equally for each data stream. © 2011 IEEE.

  16. Mutation breeding in soybean

    International Nuclear Information System (INIS)

    Baradjanegara, A.A.

    1983-01-01

    In Indonesia, soybean is one of the important crop after rice. It is generally cultivated in the lowlands and rarely in the highlands. Seeds of soybean variety ORBA were treated with various doses of fast neutrons, gamma rays, EMS and NaN 3 with the aims of studying the mutagen effects in M-1 and M-2 generations and also to select mutants adapted to highland conditions. D-50 doses for gamma rays, fast neutrons and EMS were around 23 krad, 2,300 rad, 0.3%, respectively. Much higher chlorophyll mutation frequency was observed in EMS treatment of 0.3%. Seven mutants were shorter and four early mutants matured from 4 to 20 days earlier than the control plants. Two early mutants were quite adaptable in both the low and highlands and produced better yields than the parental material. (author)

  17. Non-technical skills evaluation in the critical care air ambulance environment: introduction of an adapted rating instrument--an observational study.

    Science.gov (United States)

    Myers, Julia A; Powell, David M C; Psirides, Alex; Hathaway, Karyn; Aldington, Sarah; Haney, Michael F

    2016-03-08

    In the isolated and dynamic health-care setting of critical care air ambulance transport, the quality of clinical care is strongly influenced by non-technical skills such as anticipating, recognising and understanding, decision making, and teamwork. However there are no published reports identifying or applying a non-technical skills framework specific to an intensive care air ambulance setting. The objective of this study was to adapt and evaluate a non-technical skills rating framework for the air ambulance clinical environment. In the first phase of the project the anaesthetists' non-technical skills (ANTS) framework was adapted to the air ambulance setting, using data collected directly from clinician groups, published literature, and field observation. In the second phase experienced and inexperienced inter-hospital transport clinicians completed a simulated critical care air transport scenario, and their non-technical skills performance was independently rated by two blinded assessors. Observed and self-rated general clinical performance ratings were also collected. Rank-based statistical tests were used to examine differences in the performance of experienced and inexperienced clinicians, and relationships between different assessment approaches and assessors. The framework developed during phase one was referred to as an aeromedical non-technical skills framework, or AeroNOTS. During phase two 16 physicians from speciality training programmes in intensive care, emergency medicine and anaesthesia took part in the clinical simulation study. Clinicians with inter-hospital transport experience performed more highly than those without experience, according to both AeroNOTS non-technical skills ratings (p = 0.001) and general performance ratings (p = 0.003). Self-ratings did not distinguish experienced from inexperienced transport clinicians (p = 0.32) and were not strongly associated with either observed general performance (r(s) = 0.4, p = 0

  18. Sign and magnitude scaling properties of heart rate variability in patients with end-stage renal failure: Are these properties useful to identify pathophysiological adaptations?

    Science.gov (United States)

    Lerma, Claudia; Echeverría, Juan C.; Infante, Oscar; Pérez-Grovas, Héctor; González-Gómez, Hortensia

    2017-09-01

    The scaling properties of heart rate variability data are reliable dynamical features to predict mortality and for the assessment of cardiovascular risk. The aim of this manuscript was to determine if the scaling properties, as provided by the sign and magnitude analysis, can be used to differentiate between pathological changes and those adaptations basically introduced by modifications of the mean heart rate in distinct manoeuvres (active standing or hemodialysis treatment, HD), as well as clinical conditions (end stage renal disease, ESRD). We found that in response to active standing, the short-term scaling index (α1) increased in healthy subjects and in ESRD patients only after HD. The sign short-term scaling exponent (α1sign) increased in healthy subjects and ESRD patients, showing a less anticorrelated behavior in active standing. Both α1 and α1sign did show covariance with the mean heart rate in healthy subjects, while in ESRD patients, this covariance was observed only after HD. A reliable estimation of the magnitude short-term scaling exponent (α1magn) required the analysis of time series with a large number of samples (>3000 data points). This exponent was similar for both groups and conditions and did not show covariance with the mean heart rate. A surrogate analysis confirmed the presence of multifractal properties (α1magn > 0.5) in the time series of healthy subjects and ESDR patients. In conclusion, α1 and α1sign provided insights into the physiological adaptations during active standing, which revealed a transitory impairment before HD in ESRD patients. The presence of multifractal properties indicated that a reduced short-term variability does not necessarily imply a declined regulatory complexity in these patients.

  19. Analytical approximations of the firing rate of an adaptive exponential integrate-and-fire neuron in the presence of synaptic noise

    Directory of Open Access Journals (Sweden)

    Loreen eHertäg

    2014-09-01

    Full Text Available Computational models offer a unique tool for understanding the network-dynamical mechanisms which mediate between physiological and biophysical properties, and behavioral function. A traditional challenge in computational neuroscience is, however, that simple neuronal models which can be studied analytically fail to reproduce the diversity of electrophysiological behaviors seen in real neurons, while detailed neuronal models which do reproduce such diversity are intractable analytically and computationally expensive. A number of intermediate models have been proposed whose aim is to capture the diversity of firing behaviors and spike times of real neurons while entailing a mathematical description as simple as possible. One such model is the exponential integrate-and-fire neuron with spike rate adaptation (aEIF which consists of two differential equations for the membrane potential (V and an adaptation current (w. Despite its simplicity, it can reproduce a wide variety of physiologically observed spiking patterns, can be fit to physiological recordings quantitatively, and, once done so, is able to predict spike times on traces not used for model fitting. Here we compute the steady-state firing rate of aEIF in the presence of Gaussian synaptic noise, using two approaches. The first approach is based on the 2-dimensional Fokker-Planck equation that describes the (V,w-probability distribution, which is solved using an expansion in the ratio between the time constants of the two variables. The second is based on the firing rate of the EIF model, which is averaged over the distribution of the $w$ variable. These analytically derived closed-form expressions were tested on simulations from a large variety of model cells quantitatively fitted to in vitro electrophysiological recordings from pyramidal cells and interneurons. Theoretical predictions closely agreed with the firing rate of the simulated cells fed with in-vivo-like synaptic noise.

  20. Analytical approximations of the firing rate of an adaptive exponential integrate-and-fire neuron in the presence of synaptic noise.

    Science.gov (United States)

    Hertäg, Loreen; Durstewitz, Daniel; Brunel, Nicolas

    2014-01-01

    Computational models offer a unique tool for understanding the network-dynamical mechanisms which mediate between physiological and biophysical properties, and behavioral function. A traditional challenge in computational neuroscience is, however, that simple neuronal models which can be studied analytically fail to reproduce the diversity of electrophysiological behaviors seen in real neurons, while detailed neuronal models which do reproduce such diversity are intractable analytically and computationally expensive. A number of intermediate models have been proposed whose aim is to capture the diversity of firing behaviors and spike times of real neurons while entailing the simplest possible mathematical description. One such model is the exponential integrate-and-fire neuron with spike rate adaptation (aEIF) which consists of two differential equations for the membrane potential (V) and an adaptation current (w). Despite its simplicity, it can reproduce a wide variety of physiologically observed spiking patterns, can be fit to physiological recordings quantitatively, and, once done so, is able to predict spike times on traces not used for model fitting. Here we compute the steady-state firing rate of aEIF in the presence of Gaussian synaptic noise, using two approaches. The first approach is based on the 2-dimensional Fokker-Planck equation that describes the (V,w)-probability distribution, which is solved using an expansion in the ratio between the time constants of the two variables. The second is based on the firing rate of the EIF model, which is averaged over the distribution of the w variable. These analytically derived closed-form expressions were tested on simulations from a large variety of model cells quantitatively fitted to in vitro electrophysiological recordings from pyramidal cells and interneurons. Theoretical predictions closely agreed with the firing rate of the simulated cells fed with in-vivo-like synaptic noise.

  1. Volatility of Mutator Phenotypes at Single Cell Resolution.

    Directory of Open Access Journals (Sweden)

    Scott R Kennedy

    2015-04-01

    Full Text Available Mutator phenotypes accelerate the evolutionary process of neoplastic transformation. Historically, the measurement of mutation rates has relied on scoring the occurrence of rare mutations in target genes in large populations of cells. Averaging mutation rates over large cell populations assumes that new mutations arise at a constant rate during each cell division. If the mutation rate is not constant, an expanding mutator population may contain subclones with widely divergent rates of evolution. Here, we report mutation rate measurements of individual cell divisions of mutator yeast deficient in DNA polymerase ε proofreading and base-base mismatch repair. Our data are best fit by a model in which cells can assume one of two distinct mutator states, with mutation rates that differ by an order of magnitude. In error-prone cell divisions, mutations occurred on the same chromosome more frequently than expected by chance, often in DNA with similar predicted replication timing, consistent with a spatiotemporal dimension to the hypermutator state. Mapping of mutations onto predicted replicons revealed that mutations were enriched in the first half of the replicon as well as near termination zones. Taken together, our findings show that individual genome replication events exhibit an unexpected volatility that may deepen our understanding of the evolution of mutator-driven malignancies.

  2. Enhancing the Frequency Adaptability of Periodic Current Controllers with a Fixed Sampling Rate for Grid-Connected Power Converters

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

    2016-01-01

    Grid-connected power converters should employ advanced current controllers, e.g., Proportional Resonant (PR) and Repetitive Controllers (RC), in order to produce high-quality feed-in currents that are required to be synchronized with the grid. The synchronization is actually to detect...... of the resonant controllers and by approximating the fractional delay using a Lagrange interpolating polynomial for the RC, respectively, the frequency-variation-immunity of these periodic current controllers with a fixed sampling rate is improved. Experiments on a single-phase grid-connected system are presented...... the instantaneous grid information (e.g., frequency and phase of the grid voltage) for the current control, which is commonly performed by a Phase-Locked-Loop (PLL) system. Hence, harmonics and deviations in the estimated frequency by the PLL could lead to current tracking performance degradation, especially...

  3. Comparison of Rooting Strategies to Explore Rock Fractures for Shallow Soil-Adapted Tree Species with Contrasting Aboveground Growth Rates: A Greenhouse Microcosm Experiment.

    Science.gov (United States)

    Nie, Yunpeng; Chen, Hongsong; Ding, Yali; Yang, Jing; Wang, Kelin

    2017-01-01

    For tree species adapted to shallow soil environments, rooting strategies that efficiently explore rock fractures are important because soil water depletion occurs frequently. However, two questions: (a) to what extent shallow soil-adapted species rely on exploring rock fractures and (b) what outcomes result from drought stress, have rarely been tested. Therefore, based on the expectation that early development of roots into deep soil layers is at the cost of aboveground growth, seedlings of three tree species ( Cyclobalanopsis glauca, Delavaya toxocarpa , and Acer cinnamomifolium ) with distinct aboveground growth rates were selected from a typical shallow soil region. In a greenhouse experiment that mimics the basic features of shallow soil environments, 1-year-old seedlings were transplanted into simulated microcosms of shallow soil overlaying fractured bedrock. Root biomass allocation and leaf physiological activities, as well as leaf δ 13 C values were investigated and compared for two treatments: regular irrigation and repeated cycles of drought stress. Our results show that the three species differed in their rooting strategies in the context of encountering rock fractures, however, these strategies were not closely related to the aboveground growth rate. For the slowest-growing seedling, C. glauca , percentages of root mass in the fractures, as well as in the soil layer between soil and bedrock increased significantly under both treatments, indicating a specialized rooting strategy that facilitated the exploration of rock fractures. Early investment in deep root growth was likely critical to the establishment of this drought-vulnerable species. For the intermediate-growing, A. cinnamomifolium , percentages of root mass in the bedrock and interface soil layers were relatively low and exhibited no obvious change under either treatment. This limited need to explore rock fractures was compensated by a conservative water use strategy. For the fast-growing, D

  4. Comparison of Rooting Strategies to Explore Rock Fractures for Shallow Soil-Adapted Tree Species with Contrasting Aboveground Growth Rates: A Greenhouse Microcosm Experiment

    Directory of Open Access Journals (Sweden)

    Yunpeng Nie

    2017-09-01

    Full Text Available For tree species adapted to shallow soil environments, rooting strategies that efficiently explore rock fractures are important because soil water depletion occurs frequently. However, two questions: (a to what extent shallow soil-adapted species rely on exploring rock fractures and (b what outcomes result from drought stress, have rarely been tested. Therefore, based on the expectation that early development of roots into deep soil layers is at the cost of aboveground growth, seedlings of three tree species (Cyclobalanopsis glauca, Delavaya toxocarpa, and Acer cinnamomifolium with distinct aboveground growth rates were selected from a typical shallow soil region. In a greenhouse experiment that mimics the basic features of shallow soil environments, 1-year-old seedlings were transplanted into simulated microcosms of shallow soil overlaying fractured bedrock. Root biomass allocation and leaf physiological activities, as well as leaf δ13C values were investigated and compared for two treatments: regular irrigation and repeated cycles of drought stress. Our results show that the three species differed in their rooting strategies in the context of encountering rock fractures, however, these strategies were not closely related to the aboveground growth rate. For the slowest-growing seedling, C. glauca, percentages of root mass in the fractures, as well as in the soil layer between soil and bedrock increased significantly under both treatments, indicating a specialized rooting strategy that facilitated the exploration of rock fractures. Early investment in deep root growth was likely critical to the establishment of this drought-vulnerable species. For the intermediate-growing, A. cinnamomifolium, percentages of root mass in the bedrock and interface soil layers were relatively low and exhibited no obvious change under either treatment. This limited need to explore rock fractures was compensated by a conservative water use strategy. For the fast

  5. 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