Science.gov

Sample records for deleterious materials

  1. Sex and deleterious mutations.

    PubMed

    Gordo, Isabel; Campos, Paulo R A

    2008-05-01

    The evolutionary advantage of sexual reproduction has been considered as one of the most pressing questions in evolutionary biology. While a pluralistic view of the evolution of sex and recombination has been suggested by some, here we take a simpler view and try to quantify the conditions under which sex can evolve given a set of minimal assumptions. Since real populations are finite and also subject to recurrent deleterious mutations, this minimal model should apply generally to all populations. We show that the maximum advantage of recombination occurs for an intermediate value of the deleterious effect of mutations. Furthermore we show that the conditions under which the biggest advantage of sex is achieved are those that produce the fastest fitness decline in the corresponding asexual population and are therefore the conditions for which Muller's ratchet has the strongest effect. We also show that the selective advantage of a modifier of the recombination rate depends on its strength. The quantification of the range of selective effects that favors recombination then leads us to suggest that, if in stressful environments the effect of deleterious mutations is enhanced, a connection between sex and stress could be expected, as it is found in several species.

  2. 21 CFR 509.6 - Added poisonous or deleterious substances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious...

  3. Deleterious Passengers in Adapting Populations

    PubMed Central

    Good, Benjamin H.; Desai, Michael M.

    2014-01-01

    Most new mutations are deleterious and are eventually eliminated by natural selection. But in an adapting population, the rapid amplification of beneficial mutations can hinder the removal of deleterious variants in nearby regions of the genome, altering the patterns of sequence evolution. Here, we analyze the interactions between beneficial “driver” mutations and linked deleterious “passengers” during the course of adaptation. We derive analytical expressions for the substitution rate of a deleterious mutation as a function of its fitness cost, as well as the reduction in the beneficial substitution rate due to the genetic load of the passengers. We find that the fate of each deleterious mutation varies dramatically with the rate and spectrum of beneficial mutations and the deleterious substitution rate depends nonmonotonically on the population size and the rate of adaptation. By quantifying this dependence, our results allow us to estimate which deleterious mutations will be likely to fix and how many of these mutations must arise before the progress of adaptation is significantly reduced. PMID:25194161

  4. Deleterious background selection with recombination

    SciTech Connect

    Hudson, R.R.; Kaplan, N.L.

    1995-12-01

    An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. 33 refs., 4 figs., 1 tab.

  5. Limited dispersal, deleterious mutations and the evolution of sex

    SciTech Connect

    Peck, J.R.

    1996-03-01

    This study presents a mathematical model that allows for some offspring to be dispersed at random, while others stay close to their mothers. A single genetic locus is assumed to control fertility, and this locus is subject to the occurrence of deletions mutations. It is shown that, at equilibrium, the frequency of deleterious mutations in the population is inversely related to the rate of dispersal. The results also show that sexual reproduction can lead to a decrease in the equilibrium frequency of deleterious mutations. The reason for this relationship is that sex involves the dispersal of genetic material, and thus, like the dispersal of offspring, sex enhances competition among adults. The model is described using the example of a hermaphroditic plant population. However, the results should apply to animal populations as well. 36 refs., 1 fig.

  6. Deleterious mutation and the evolution of eusociality.

    PubMed

    Cherry, Joshua L

    2002-12-01

    Certain arguments concerning the evolution of eusociality form a classic example of the application of the principles of kin selection. These arguments center on the different degrees of relatedness of potential beneficiaries of an individual's efforts, for example a female's higher relatedness to her sisters than to her daughters in a haplodiploid system. This type of reasoning is insufficicnt to account for the evolution and maintainence of sexual reproduction, because parthenogenic females produce offspring that are more closely related to them than are offspring produced sexually. Among the forces invoked to explain sexual reproduction is deleterious mutation. This factor can be shown to favor eusociality as well, because siblings produced by helping carry fewer deleterious alleles on average than would offspring. The strength of this effect depends on the genomewide deleterious mutation rate, U, and on the selection coefficient, s, associated with deleterious alleles. For small s, the effect depends approximately on the product Us. This phenomenon illustrates that an assumption implicit in some analyses-that the relatedness of an individual to an actor is all that matters to its value to that actor-can fail for the evolution of eusociality as it does for the evolution of sex. PMID:12583576

  7. Validation of Deleterious Mutations in Vorderwald Cattle

    PubMed Central

    Reinartz, Sina; Distl, Ottmar

    2016-01-01

    In Montbéliarde cattle two candidate mutations on bovine chromosomes 19 and 29 responsible for embryonic lethality have been detected. Montbéliarde bulls have been introduced into Vorderwald cattle to improve milk and fattening performance. Due to the small population size of Vorderwald cattle and the wide use of a few Montbéliarde bulls through artificial insemination, inbreeding on Montbéliarde bulls in later generations was increasing. Therefore, we genotyped an aborted fetus which was inbred on Montbéliarde as well as Vorderwald x Montbéliarde crossbred bulls for both deleterious mutations. The abortion was observed in an experimental herd of Vorderwald cattle. The objectives of the present study were to prove if one or both lethal mutations may be assumed to have caused this abortion and to show whether these deleterious mutations have been introduced into the Vorderwald cattle population through Montbéliarde bulls. The aborted fetus was homozygous for the SLC37A2:g.28879810C>T mutation (ss2019324563) on BTA29 and both parents as well as the paternal and maternal grandsire were heterozygous for this mutation. In addition, the parents and the paternal grandsire were carriers of the MH2-haplotype linked with the T-allele of the SLC37A2:g.28879810C>T mutation. For the SHBG:g.27956790C>T mutation (rs38377500) on BTA19 (MH1), the aborted fetus and its sire were heterozygous. Among all further 341 Vorderwald cattle genotyped we found 27 SLC37A2:g.28879810C>T heterozygous animals resulting in an allele frequency of 0.0396. Among the 120 male Vorderwald cattle, there were 12 heterozygous with an allele frequency of 0.05. The SLC37A2:g.28879810C>T mutation could not be found in further nine cattle breeds nor in Vorderwald cattle with contributions from Ayrshire bulls. In 69 Vorderwald cattle without genes from Montbéliarde bulls the mutated allele of SLC37A2:g.28879810C>T could not be detected. The SHBG:g.27956790C>T mutation appeared unlikely to be responsible

  8. Validation of Deleterious Mutations in Vorderwald Cattle.

    PubMed

    Reinartz, Sina; Distl, Ottmar

    2016-01-01

    In Montbéliarde cattle two candidate mutations on bovine chromosomes 19 and 29 responsible for embryonic lethality have been detected. Montbéliarde bulls have been introduced into Vorderwald cattle to improve milk and fattening performance. Due to the small population size of Vorderwald cattle and the wide use of a few Montbéliarde bulls through artificial insemination, inbreeding on Montbéliarde bulls in later generations was increasing. Therefore, we genotyped an aborted fetus which was inbred on Montbéliarde as well as Vorderwald x Montbéliarde crossbred bulls for both deleterious mutations. The abortion was observed in an experimental herd of Vorderwald cattle. The objectives of the present study were to prove if one or both lethal mutations may be assumed to have caused this abortion and to show whether these deleterious mutations have been introduced into the Vorderwald cattle population through Montbéliarde bulls. The aborted fetus was homozygous for the SLC37A2:g.28879810C>T mutation (ss2019324563) on BTA29 and both parents as well as the paternal and maternal grandsire were heterozygous for this mutation. In addition, the parents and the paternal grandsire were carriers of the MH2-haplotype linked with the T-allele of the SLC37A2:g.28879810C>T mutation. For the SHBG:g.27956790C>T mutation (rs38377500) on BTA19 (MH1), the aborted fetus and its sire were heterozygous. Among all further 341 Vorderwald cattle genotyped we found 27 SLC37A2:g.28879810C>T heterozygous animals resulting in an allele frequency of 0.0396. Among the 120 male Vorderwald cattle, there were 12 heterozygous with an allele frequency of 0.05. The SLC37A2:g.28879810C>T mutation could not be found in further nine cattle breeds nor in Vorderwald cattle with contributions from Ayrshire bulls. In 69 Vorderwald cattle without genes from Montbéliarde bulls the mutated allele of SLC37A2:g.28879810C>T could not be detected. The SHBG:g.27956790C>T mutation appeared unlikely to be responsible

  9. The Role of Deleterious Substitutions in Crop Genomes

    PubMed Central

    Kono, Thomas J. Y.; Fu, Fengli; Mohammadi, Mohsen; Hoffman, Paul J.; Liu, Chaochih; Stupar, Robert M.; Smith, Kevin P.; Tiffin, Peter; Fay, Justin C.; Morrell, Peter L.

    2016-01-01

    Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects of new mutations is not directly observable, many mutations likely either have no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of 15 barley accessions and genome resequencing of 8 soybean accessions to investigate the prevalence of deleterious single nucleotide polymorphisms (SNPs) in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach identifies known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool BAD_Mutations that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes. PMID:27301592

  10. 21 CFR 509.6 - Added poisonous or deleterious substances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS UNAVOIDABLE CONTAMINANTS IN ANIMAL FOOD AND FOOD... poisonous or deleterious substance, other than a pesticide chemical, that is also a food additive will be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Added poisonous or deleterious substances....

  11. 21 CFR 109.6 - Added poisonous or deleterious substances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) FOOD FOR HUMAN CONSUMPTION UNAVOIDABLE CONTAMINANTS IN FOOD FOR HUMAN CONSUMPTION AND FOOD... poisonous or deleterious substance, other than a pesticide chemical, that is also a food additive, will be... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Added poisonous or deleterious substances....

  12. Deleterious mutations and selection for sex in finite diploid populations.

    PubMed

    Roze, Denis; Michod, Richard E

    2010-04-01

    In diploid populations, indirect benefits of sex may stem from segregation and recombination. Although it has been recognized that finite population size is an important component of selection for recombination, its effects on selection for segregation have been somewhat less studied. In this article, we develop analytical two- and three-locus models to study the effect of recurrent deleterious mutations on a modifier gene increasing sex, in a finite diploid population. The model also incorporates effects of mitotic recombination, causing loss of heterozygosity (LOH). Predictions are tested using multilocus simulations representing deleterious mutations occurring at a large number of loci. The model and simulations show that excess of heterozygosity generated by finite population size is an important component of selection for sex, favoring segregation when deleterious alleles are nearly additive to dominant. Furthermore, sex tends to break correlations in homozygosity among selected loci, which disfavors sex when deleterious alleles are either recessive or dominant. As a result, we find that it is difficult to maintain costly sex when deleterious alleles are recessive. LOH tends to favor sex when deleterious mutations are recessive, but the effect is relatively weak for rates of LOH corresponding to current estimates (of the order 10(-4)-10(-5)).

  13. Efficient purging of deleterious mutations in plants with haploid selfing

    SciTech Connect

    Szovenyi, Peter; Shaw, Jon; Yang, Xiaohan; Devos, Nicolas

    2014-05-30

    In diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly more non-synonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale.

  14. Efficient Purging of Deleterious Mutations in Plants with Haploid Selfing

    PubMed Central

    Szövényi, Péter; Devos, Nicolas; Weston, David J.; Yang, Xiaohan; Hock, Zsófia; Shaw, Jonathan A.; Shimizu, Kentaro K.; McDaniel, Stuart F.; Wagner, Andreas

    2014-01-01

    In diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here, we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly more nonsynonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale. PMID:24879432

  15. Efficient purging of deleterious mutations in plants with haploid selfing.

    PubMed

    Szövényi, Péter; Devos, Nicolas; Weston, David J; Yang, Xiaohan; Hock, Zsófia; Shaw, Jonathan A; Shimizu, Kentaro K; McDaniel, Stuart F; Wagner, Andreas

    2014-05-01

    In diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here, we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly more nonsynonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale. PMID:24879432

  16. Deleterious oral habits in children with hearing impairment

    PubMed Central

    SUHANI, RALUCA DIANA; SUHANI, MIHAI FLAVIU; MUNTEAN, ALEXANDRINA; MESAROS, MICHAELA; BADEA, MINDRA EUGENIA

    2015-01-01

    Background and aims Deleterious oral habits represent a serious public health issue. The information available about this problem in children with hearing impairment is insufficient. The purpose of this study was to investigate the prevalence of deleterious oral habits among children with hearing impairment and comparing results against children without hearing impairment. Method This epidemiological study was carried out in a sample size of 315 children. We used a random sampling technique that included 150 children with hearing impairment and 165 without hearing impairment. All subjects were submitted to a clinical examination. The parents/legal guardians were asked to complete a questionnaire regarding the deleterious habits of their children. Results The data collected indicated a higher prevalence of deleterious oral habits among children with hearing impairment: 53.3% as opposed to 40.6% among children without hearing impairment. There was a higher incidence of malocclusion in children with hearing impairment (79.3%) compared to children without hearing impairment (57%). Conclusions This study highlighted the need to establish protocols for preventive orthodontic treatment at an early age, in order to reduce the deleterious oral habits and prevent malocclusion. Dental institutions/clinicians need to implement oral care programs including proper oral education aiming to promote oral health. PMID:26609277

  17. The deleterious mutation load is insensitive to recent population history

    PubMed Central

    Simons, Yuval B.; Turchin, Michael C.; Pritchard, Jonathan K.; Sella, Guy

    2014-01-01

    Human populations have undergone dramatic changes in population size in the past 100,000 years, including recent rapid growth. How these demographic events have affected the burden of deleterious mutations in individuals and the frequencies of disease mutations in populations remains unclear. We use population genetic models to show that recent human demography has likely had little impact on the average burden of deleterious mutations. This prediction is supported by two exome sequence datasets showing that individuals of west African and European ancestry carry very similar burdens of damaging mutations. We further show that for many diseases, rare alleles are unlikely to contribute a large fraction of the heritable variation, and therefore the impact of recent growth is likely to be modest. However, for those diseases that have a direct impact on fitness, strongly deleterious rare mutations likely do play an important role, and recent growth will have increased their impact. PMID:24509481

  18. Obstruction of adaptation in diploids by recessive, strongly deleterious alleles

    PubMed Central

    Assaf, Zoe June; Petrov, Dmitri A.; Blundell, Jamie R.

    2015-01-01

    Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a “staggered sweep.” It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila. PMID:25941393

  19. Nonequilibrium model for estimating parameters of deleterious mutations

    NASA Astrophysics Data System (ADS)

    Gordo, Isabel; Dionisio, Francisco

    2005-03-01

    Deleterious mutations are of extreme evolutionary importance because, even though they are eliminated by natural selection, their continuous pressure creates a pool of variability in natural populations. They are of potential relevance for the existence of several features in evolution, such as sexual reproduction, and pose a risk to small asexual populations. Despite their extreme importance, the deleterious mutation rate and the effects of each mutation on fitness are poorly known quantities. Here we analyze a simple model that can be applied to simple experiments, in microorganisms, aiming at the quantification of these values.

  20. Influence of the grain size on deleterious phase precipitation in superduplex stainless steel UNS S32750

    SciTech Connect

    Pardal, J.M.

    2009-03-15

    In the present work, the effect of grain size on deleterious phase precipitation in a superduplex stainless steel was investigated. The materials studied were heat treated isothermally at 800 deg. C, 850 deg. C and 900 deg. C for times up to 120 min. Hardness tests, light optical microscopy, scanning electron microscopy and X-ray diffraction were carried out to detect sigma and other harmful precipitate phases. The ferritic and austenitic grain sizes in the solution treated condition of the two steels analyzed were measured by electron backscattered diffraction (EBSD). Cyclic polarization corrosion tests were performed to evaluate the effect of grain size on the corrosion resistance. The results presented show that the precipitation of deleterious phases such as {chi}, {sigma} and {gamma}{sub 2}, which can occur during welding and forming operations, is retarded by grain growth.

  1. Prevention of deleterious deposits in a coal liquefaction system

    DOEpatents

    Carr, Norman L.; Prudich, Michael E.; King, Jr., William E.; Moon, William G.

    1984-07-03

    A process for preventing the formation of deleterious coke deposits on the walls of coal liquefaction reactor vessels involves passing hydrogen and a feed slurry comprising feed coal and recycle liquid solvent to a coal liquefaction reaction zone while imparting a critical mixing energy of at least 3500 ergs per cubic centimeter of reaction zone volume per second to the reacting slurry.

  2. 21 CFR 109.6 - Added poisonous or deleterious substances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 109.6 Section 109.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION UNAVOIDABLE CONTAMINANTS IN FOOD FOR HUMAN CONSUMPTION AND...

  3. Accumulation of Deleterious Mutations Near Sexually Antagonistic Genes

    PubMed Central

    Connallon, Tim; Jordan, Crispin Y.

    2016-01-01

    Mutation generates a steady supply of genetic variation that, while occasionally useful for adaptation, is more often deleterious for fitness. Recent research has emphasized that the fitness effects of mutations often differ between the sexes, leading to important evolutionary consequences for the maintenance of genetic variation and long-term population viability. Some forms of sex-specific selection—i.e., stronger purifying selection in males than females—can help purge a population’s load of female-harming mutations and promote population growth. Other scenarios—e.g., sexually antagonistic selection, in which mutations that harm females are beneficial for males—inflate genetic loads and potentially dampen population viability. Evolutionary processes of sexual antagonism and purifying selection are likely to impact the evolutionary dynamics of different loci within a genome, yet theory has mostly ignored the potential for interactions between such loci to jointly shape the evolutionary genetic basis of female and male fitness variation. Here, we show that sexually antagonistic selection at a locus tends to elevate the frequencies of deleterious alleles at tightly linked loci that evolve under purifying selection. Moreover, haplotypes that segregate for different sexually antagonistic alleles accumulate different types of deleterious mutations. Haplotypes that carry female-benefit sexually antagonistic alleles preferentially accumulate mutations that are primarily male harming, whereas male-benefit haplotypes accumulate mutations that are primarily female harming. The theory predicts that sexually antagonistic selection should shape the genomic organization of genetic variation that differentially impacts female and male fitness, and contribute to sexual dimorphism in the genetic basis of fitness variation. PMID:27226163

  4. Accumulation of Deleterious Mutations Near Sexually Antagonistic Genes.

    PubMed

    Connallon, Tim; Jordan, Crispin Y

    2016-01-01

    Mutation generates a steady supply of genetic variation that, while occasionally useful for adaptation, is more often deleterious for fitness. Recent research has emphasized that the fitness effects of mutations often differ between the sexes, leading to important evolutionary consequences for the maintenance of genetic variation and long-term population viability. Some forms of sex-specific selection-i.e., stronger purifying selection in males than females-can help purge a population's load of female-harming mutations and promote population growth. Other scenarios-e.g., sexually antagonistic selection, in which mutations that harm females are beneficial for males-inflate genetic loads and potentially dampen population viability. Evolutionary processes of sexual antagonism and purifying selection are likely to impact the evolutionary dynamics of different loci within a genome, yet theory has mostly ignored the potential for interactions between such loci to jointly shape the evolutionary genetic basis of female and male fitness variation. Here, we show that sexually antagonistic selection at a locus tends to elevate the frequencies of deleterious alleles at tightly linked loci that evolve under purifying selection. Moreover, haplotypes that segregate for different sexually antagonistic alleles accumulate different types of deleterious mutations. Haplotypes that carry female-benefit sexually antagonistic alleles preferentially accumulate mutations that are primarily male harming, whereas male-benefit haplotypes accumulate mutations that are primarily female harming. The theory predicts that sexually antagonistic selection should shape the genomic organization of genetic variation that differentially impacts female and male fitness, and contribute to sexual dimorphism in the genetic basis of fitness variation. PMID:27226163

  5. RNA chaperones buffer deleterious mutations in E. coli

    PubMed Central

    Rudan, Marina; Schneider, Dominique; Warnecke, Tobias; Krisko, Anita

    2015-01-01

    Both proteins and RNAs can misfold into non-functional conformations. Protein chaperones promote native folding of nascent polypeptides and refolding of misfolded species, thereby buffering mutations that compromise protein structure and function. Here, we show that RNA chaperones can also act as mutation buffers that enhance organismal fitness. Using competition assays, we demonstrate that overexpression of select RNA chaperones, including three DEAD box RNA helicases (DBRHs) (CsdA, SrmB, RhlB) and the cold shock protein CspA, improves fitness of two independently evolved Escherichia coli mutator strains that have accumulated deleterious mutations during short- and long-term laboratory evolution. We identify strain-specific mutations that are deleterious and subject to buffering when introduced individually into the ancestral genotype. For DBRHs, we show that buffering requires helicase activity, implicating RNA structural remodelling in the buffering process. Our results suggest that RNA chaperones might play a fundamental role in RNA evolution and evolvability. DOI: http://dx.doi.org/10.7554/eLife.04745.001 PMID:25806682

  6. Sex-chromosome turnovers induced by deleterious mutation load.

    PubMed

    Blaser, Olivier; Grossen, Christine; Neuenschwander, Samuel; Perrin, Nicolas

    2013-03-01

    In sharp contrast with mammals and birds, many cold-blooded vertebrates present homomorphic sex chromosomes. Empirical evidence supports a role for frequent turnovers, which replace nonrecombining sex chromosomes before they have time to decay. Three main mechanisms have been proposed for such turnovers, relying either on neutral processes, sex-ratio selection, or intrinsic benefits of the new sex-determining genes (due, e.g., to linkage with sexually antagonistic mutations). Here, we suggest an additional mechanism, arising from the load of deleterious mutations that accumulate on nonrecombining sex chromosomes. In the absence of dosage compensation, this load should progressively lower survival rate in the heterogametic sex. Turnovers should occur when this cost outweighs the benefits gained from any sexually antagonistic genes carried by the nonrecombining sex chromosome. We use individual-based simulations of a Muller's ratchet process to test this prediction, and investigate how the relevant parameters (effective population size, strength and dominance of deleterious mutations, size of nonrecombining segment, and strength of sexually antagonistic selection) are expected to affect the rate of turnovers. PMID:23461315

  7. A bird's eye view of a deleterious recessive allele.

    PubMed

    Ekblom, Robert

    2016-07-01

    In the endangered Scottish chough (Pyrrhocorax pyrrhocorax) population, a lethal blindness syndrome is found to be caused by a deleterious recessive allele. Photo: Gordon Yates. In Focus: Trask, A.E., Bignal, E.M., McCracken, D.I., Monaghan, P., Piertney, S.B. & Reid, J.M. (2016) Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. Journal of Animal Ecology, 85, 879-891. In this issue of Journal of Animal Ecology, Trask et al. () report on a strange, lethal, blindness that regularly affects chicks of an endangered bird population. The authors show that the inheritance mode of this blindness disease precisely matches the expectations of a recessive deleterious mutation. Intriguingly, there is also an indication that the disease-causing variant might be maintained in the population by balancing selection, due to a selective advantage for heterozygotes. Could this finding have consequences for conservation actions implemented for the population? PMID:27279331

  8. The Effects of Deleterious Mutations on Evolution at Linked Sites

    PubMed Central

    Charlesworth, Brian

    2012-01-01

    The process of evolution at a given site in the genome can be influenced by the action of selection at other sites, especially when these are closely linked to it. Such selection reduces the effective population size experienced by the site in question (the Hill–Robertson effect), reducing the level of variability and the efficacy of selection. In particular, deleterious variants are continually being produced by mutation and then eliminated by selection at sites throughout the genome. The resulting reduction in variability at linked neutral or nearly neutral sites can be predicted from the theory of background selection, which assumes that deleterious mutations have such large effects that their behavior in the population is effectively deterministic. More weakly selected mutations can accumulate by Muller’s ratchet after a shutdown of recombination, as in an evolving Y chromosome. Many functionally significant sites are probably so weakly selected that Hill–Robertson interference undermines the effective strength of selection upon them, when recombination is rare or absent. This leads to large departures from deterministic equilibrium and smaller effects on linked neutral sites than under background selection or Muller’s ratchet. Evidence is discussed that is consistent with the action of these processes in shaping genome-wide patterns of variation and evolution. PMID:22219506

  9. Paradoxical Roles of the Neutrophil in Sepsis: Protective and Deleterious

    PubMed Central

    Sônego, Fabiane; Castanheira, Fernanda Vargas e Silva; Ferreira, Raphael Gomes; Kanashiro, Alexandre; Leite, Caio Abner Vitorino Gonçalves; Nascimento, Daniele Carvalho; Colón, David Fernando; Borges, Vanessa de Fátima; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2016-01-01

    Sepsis, an overwhelming inflammatory response syndrome secondary to infection, is one of the costliest and deadliest medical conditions worldwide. Neutrophils are classically considered to be essential players in the host defense against invading pathogens. However, several investigations have shown that impairment of neutrophil migration to the site of infection, also referred to as neutrophil paralysis, occurs during severe sepsis, resulting in an inability of the host to contain and eliminate the infection. On the other hand, the neutrophil antibacterial arsenal contributes to tissue damage and the development of organ dysfunction during sepsis. In this review, we provide an overview of the main events in which neutrophils play a beneficial or deleterious role in the outcome of sepsis. PMID:27199981

  10. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  11. Cells that produce deleterious autoreactive antibodies are vulnerable to suicide.

    PubMed

    Niu, Haitao; Leung, Danny T M; Ma, Chun Hung; Law, Eric C Y; Tam, Frankie C H; Lim, Pak-Leong

    2008-08-01

    It is puzzling how autoreactive B cells that escape self-tolerance mechanisms manage to produce Abs that target vital cellular processes without succumbing themselves to the potentially deleterious effects of these proteins. We report that censorship indeed exists at this level: when the Ab synthesis in the cell is up-regulated in IL-6-enriched environments (e.g., adjuvant-primed mouse peritoneum), the cell dies of the increased intracellular binding between the Ab and the cellular autoantigen. In the case in which telomerase is the autoantigen, mouse hybridoma cells synthesizing such an autoantibody, which appeared to grow well in culture, could not grow in syngeneic BALB/c mice to form ascites, but grew nevertheless in athymic siblings. Culture experiments demonstrated that peritoneal cell-derived IL-6 (and accessory factors) affected the growth and functions of the hybridoma cells, including the induction of mitochondria-based apoptosis. Electron microscopy revealed an abundance of Abs in the nuclear chromatin of IL-6-stimulated cells, presumably piggy-backed there by telomerase from the cytosol. This nuclear presence was confirmed by light microscopy analysis of isolated nuclei. In two other cases, hybridoma cells synthesizing an autoantibody to GTP or osteopontin also showed similar growth inhibition in vivo. In all cases, Ab function was crucial to the demise of the cells. Thus, autoreactive cells, which synthesize autoantibodies to certain intracellular Ags, live delicately between life and death depending on the cytokine microenvironment. Paradoxically, IL-6, which is normally growth-potentiating for B cells, is proapoptotic for these cells. The findings reveal potential strategies and targets for immunotherapy. PMID:18641365

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

    PubMed Central

    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

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

    PubMed

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

    2013-08-20

    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.

  14. Europeans have a higher proportion of high‑frequency deleterious variants than Africans.

    PubMed

    Subramanian, Sankar

    2016-01-01

    Recent studies have shown that a high proportion of rare variants in European and African populations are deleterious in nature. However, the deleterious fraction of high-frequency variants is unclear. Using more than 6500 exomes we show a much higher fraction (11 %) of relatively high-frequency nonsynonymous (amino acid altering) variants (DAF 0.1–10 %) in European Americans (EA) compared to those from African Americans (AA). In contrast, this difference was only marginal (<2 %) for low-frequency nonsynonymous variants (DAF <0.1 %). Our results also revealed that the proportion of high-frequency deleterious nonsynonymous variants in EA was much higher (24 %) than that in AA and this difference was very small (4 %) for the low-frequency deleterious amino acid altering variants. We also show that EA have significantly more number of high-frequency deleterious nonsynonymous variants per genome than AA. The high proportion of high-frequency deleterious variants in EA could be the result of the well-known bottleneck experienced by European populations in which harmful mutations may have drifted to high frequencies. The estimated ages of deleterious variants support this prediction. Our results suggest that high-frequency variants could be relatively more likely to be associated with diseases in Europeans than in Africans and hence emphasize the need for population-specific strategies in genomic medicine studies.

  15. Characteristics of neutral and deleterious protein-coding variation among individuals and populations.

    PubMed

    Fu, Wenqing; Gittelman, Rachel M; Bamshad, Michael J; Akey, Joshua M

    2014-10-01

    Whole-genome and exome data sets continue to be produced at a frenetic pace, resulting in massively large catalogs of human genomic variation. However, a clear picture of the characteristics and patterns of neutral and deleterious variation within and between populations has yet to emerge, given that recent large-scale sequencing studies have often emphasized different aspects of the data and sometimes appear to have conflicting conclusions. Here, we comprehensively studied characteristics of protein-coding variation in high-coverage exome sequence data from 6,515 European American (EA) and African American (AA) individuals. We developed an unbiased approach to identify putatively deleterious variants and investigated patterns of neutral and deleterious single-nucleotide variants and alleles between individuals and populations. We show that there are substantial differences in the composition of genotypes between EA and AA populations and that small but statistically significant differences exist in the average number of deleterious alleles carried by EA and AA individuals. Furthermore, we performed extensive simulations to delineate the temporal dynamics of deleterious alleles for a broad range of demographic models and use these data to inform the interpretation of empirical patterns of deleterious variation. Finally, we illustrate that the effects of demographic perturbations, such as bottlenecks and expansions, often manifest in opposing patterns of neutral and deleterious variation depending on whether the focus is on populations or individuals. Our results clarify seemingly disparate empirical characteristics of protein-coding variation and provide substantial insights into how natural selection and demographic history have patterned neutral and deleterious variation within and between populations. PMID:25279984

  16. Spatial heterogeneity in the strength of selection against deleterious alleles and the mutation load.

    PubMed

    Roze, D

    2012-09-01

    According to current estimates of genomic deleterious mutation rates (which are often of the order 0.1-1) the mutation load (defined as a reduction in the average fitness of a population due to the presence of deleterious alleles) may be important in many populations. In this paper, I use multilocus simulations to explore the effect of spatial heterogeneity in the strength of selection against deleterious alleles on the mutation load (for example, it has been suggested that stressful environments may increase the strength of selection). These simulations show contrasted results: in some situations, spatial heterogeneity may greatly reduce the mutation load, due to the fact that migrants coming from demes under stronger selection carry relatively few deleterious alleles, and benefit from a strong advantage within demes under weaker selection (where individuals carry many more deleterious alleles); in other situations, however, deleterious alleles accumulate within demes under stronger selection, due to migration pressure from demes under weaker selection, leading to fitness erosion within those demes. This second situation is more frequent when the productivity of the different demes is proportional to their mean fitness. The effect of spatial heterogeneity is greatly reduced, however, when the response to environmental differences is inconsistent across loci.

  17. Estimate of the genomic mutation rate deleterious to overall fitness in E. coll

    NASA Astrophysics Data System (ADS)

    Kibota, Travis T.; Lynch, Michael

    1996-06-01

    MUTATIONS are a double-edged sword: they are the ultimate source of genetic variation upon which evolution depends, yet most mutations affecting fitness (viability and reproductive success) appear to be harmful1. Deleterious mutations of small effect can escape natural selection, and should accumulate in small populations2-4. Reduced fitness from deleterious-mutation accumulation may be important in the evolution of sex5-7, mate choice8,9, and diploid life-cycles10, and in the extinction of small populations11,12. Few empirical data exist, however. Minimum estimates of the genomic deleterious-mutation rate for viability in Drosophila melanogaster are surprisingly high1,13,14, leading to the conjecture that the rate for total fitness could exceed 1.0 mutation per individual per generation5,6. Here we use Escherichia coli to provide an estimate of the genomic deleterious-mutation rate for total fitness in a microbe. We estimate that the per-microbe rate of deleterious mutations is in excess of 0.0002.

  18. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection

    PubMed Central

    Lenz, Tobias L.; Spirin, Victor; Jordan, Daniel M.; Sunyaev, Shamil R.

    2016-01-01

    Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here, we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole-exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in nonhuman leukocyte antigen (non-HLA) genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases. PMID:27436009

  19. Antagonistic coevolution with parasites increases the cost of host deleterious mutations

    PubMed Central

    Buckling, Angus; Wei, Yan; Massey, Ruth C; Brockhurst, Michael A; Hochberg, Michael E

    2005-01-01

    The fitness consequences of deleterious mutations are sometimes greater when individuals are parasitized, hence parasites may result in the more rapid purging of deleterious mutations from host populations. The significance of host deleterious mutations when hosts and parasites antagonistically coevolve (reciprocal evolution of host resistance and parasite infectivity) has not previously been experimentally investigated. We addressed this by coevolving the bacterium Pseudomonas fluorescens and a parasitic bacteriophage in laboratory microcosms, using bacteria with high and low mutation loads. Directional coevolution between bacterial resistance and phage infectivity occurred in all populations. Bacterial population fitness, as measured by competition experiments with ancestral genotypes in the absence of phage, declined with time spent coevolving. However, this decline was significantly more rapid in bacteria with high mutation loads, suggesting the cost of bacterial resistance to phage was greater in the presence of deleterious mutations (synergistic epistasis). As such, resistance to phage was more costly to evolve in the presence of a high mutation load. Consistent with these data, bacteria with high mutation loads underwent less rapid directional coevolution with their phage populations, and showed lower levels of resistance to their coevolving phage populations. These data suggest that coevolution with parasites increases the rate at which deleterious mutations are purged from host populations. PMID:16519233

  20. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel.

    PubMed

    González-Pérez, Abel; López-Bigas, Nuria

    2011-04-01

    Several large ongoing initiatives that profit from next-generation sequencing technologies have driven--and in coming years will continue to drive--the emergence of long catalogs of missense single-nucleotide variants (SNVs) in the human genome. As a consequence, researchers have developed various methods and their related computational tools to classify these missense SNVs as probably deleterious or probably neutral polymorphisms. The outputs produced by each of these computational tools are of different natures and thus difficult to compare and integrate. Taking advantage of the possible complementarity between different tools might allow more accurate classifications. Here we propose an effective approach to integrating the output of some of these tools into a unified classification; this approach is based on a weighted average of the normalized scores of the individual methods (WAS). (In this paper, the approach is illustrated for the integration of five tools.) We show that this WAS outperforms each individual method in the task of classifying missense SNVs as deleterious or neutral. Furthermore, we demonstrate that this WAS can be used not only for classification purposes (deleterious versus neutral mutation) but also as an indicator of the impact of the mutation on the functionality of the mutant protein. In other words, it may be used as a deleteriousness score of missense SNVs. Therefore, we recommend the use of this WAS as a consensus deleteriousness score of missense mutations (Condel). PMID:21457909

  1. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection.

    PubMed

    Lenz, Tobias L; Spirin, Victor; Jordan, Daniel M; Sunyaev, Shamil R

    2016-10-01

    Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here, we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole-exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in nonhuman leukocyte antigen (non-HLA) genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases. PMID:27436009

  2. Parasites and deleterious mutations: interactions influencing the evolutionary maintenance of sex.

    PubMed

    Park, A W; Jokela, J; Michalakis, Y

    2010-05-01

    The restrictive assumptions associated with purely genetic and purely ecological mechanisms suggest that neither of the two forces, in isolation, can offer a general explanation for the evolutionary maintenance of sex. Consequently, attention has turned to pluralistic models (i.e. models that apply both ecological and genetic mechanisms). Existing research has shown that combining mutation accumulation and parasitism allows restrictive assumptions about genetic and parasite parameter values to be relaxed while still predicting the maintenance of sex. However, several empirical studies have shown that deleterious mutations and parasitism can reduce fitness to a greater extent than would be expected if the two acted independently. We show how interactions between these genetic and ecological forces can completely reverse predictions about the evolution of reproductive modes. Moreover, we demonstrate that synergistic interactions between infection and deleterious mutations can render sex evolutionarily stable even when there is antagonistic epistasis among deleterious mutations, thereby widening the conditions for the evolutionary maintenance of sex.

  3. The accumulation of deleterious mutations within the frozen niche variation hypothesis.

    PubMed

    Pound, G E; Cox, S J; Doncaster, C P

    2004-05-01

    The frozen niche variation hypothesis proposes that asexual clones exploit a fraction of a total resource niche available to the sexual population from which they arise. Differences in niche breadth may allow a period of coexistence between a sexual population and the faster reproducing asexual clones. Here, we model the longer term threat to the persistence of the sexual population from an accumulation of clonal diversity, balanced by the cost to the asexual population resulting from a faster rate of accumulation of deleterious mutations. We use Monte-Carlo simulations to quantify the interaction of niche breadth with accumulating deleterious mutations. These two mechanisms may act synergistically to prevent the extinction of the sexual population, given: (1) sufficient genetic variation, and consequently niche breadth, in the sexual population; (2) a relatively slow rate of accumulation of genetic diversity in the clonal population; (3) synergistic epistasis in the accumulation of deleterious mutations. PMID:15149407

  4. The Genomic Load of Deleterious Mutations: Relevance to Death in Infancy and Childhood

    PubMed Central

    Morris, James Alfred

    2015-01-01

    The human diploid genome has approximately 40,000 functioning conserved genes distributed within 6 billion base pairs of DNA. Most individuals carry a few heterozygous deleterious mutations and this leads to an increased risk of recessive disease in the offspring of cousin unions. Rare recessive disease is more common in the children of cousin marriages than in the general population, even though <1% of marriages in the Western World are between first cousins. But more than 90% of the children of cousin marriages do not have recessive disease and are as healthy as the rest of the population. A mathematical model based on these observations generates simultaneous equations linking the mean number of deleterious mutations in the genome of adults (M), the mean number of new deleterious mutations arising in gametogenesis and passed to the next generation (N) and the number of genes in the human diploid genome (L). The best estimates are that M is <7 and N is approximately 1. The nature of meiosis indicates that deleterious mutations in zygotes will have a Poisson distribution with a mean of M + N. There must be strong selective pressure against zygotes at the upper end of the Poisson distribution otherwise the value of M would rise with each generation. It is suggested that this selection is based on synergistic interaction of heterozygous deleterious mutations acting in large complex highly redundant and robust genetic networks. To maintain the value of M in single figures over many thousands of generations means that the zygote loss must be of the order of 30%. Most of this loss will occur soon after conception but some will occur later; during fetal development, in infancy and even in childhood. Selection means genetic death and this is caused by disease to which the deleterious mutations predispose. In view of this genome sequencing should be undertaken in all infant deaths in which the cause of death is not ascertained by standard techniques. PMID:25852684

  5. Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

    PubMed

    Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

    2016-01-01

    Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.

  6. Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

    PubMed Central

    Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.

    2016-01-01

    Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

  7. Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

    PubMed

    Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

    2016-01-01

    Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

  8. [Study on species and valence state of heavy metals and deleterious elements of mineral medicine].

    PubMed

    Han, Xu; Luo, Jiao-yang; Liu, Qiu-tao; Li, Yan-jun; Xie, Yan-jun; Yang, Shi-hai; Yang, Mei-hua

    2015-12-01

    As an important part of traditional Chinese medicine (TCM), mineral medicine plays an irreplaceable role. However, little has been reported on its species and valence state of heavy metals and deleterious elements, and also the relevance to pharmacological effect and toxicology. The present paper, in a new perspective, summarized the determination of the species and valence state of heavy metals and deleterious elements in recent years, discussed the progress of the pharmacological effect and toxicology, and prospected for future study which might provide reference for mineral medicine. PMID:27141663

  9. A study of deleterious gene structure in plants using Markov chain Monte Carlo.

    PubMed

    Lee, J K; Lascoux, M; Newton, M A; Nordheim, E V

    1999-06-01

    The characteristics of deleterious genes have been of great interest in both theory and practice in genetics. Because of the complex genetic mechanism of these deleterious genes, most current studies try to estimate the overall magnitude of mortality effects on a population, which is characterized classically by the number of lethal equivalents. This number is a combination of several parameters, each of which has a distinct biological effect on genetic mortality. In conservation and breeding programs, it is important to be able to distinguish among different combinations of these parameters that lead to the same number of lethal equivalents, such as a large number of mildly deleterious genes or a few lethal genes, The ability to distinguish such parameter combinations requires more than one generation of mating. We propose a model for survival data from a two-generation mating experiment on the plant species Brassica rapa, and we enable inference with Markov chain Monte Carlo. This computational strategy is effective because a vast amount of missing genotype information must be accounted for. In addition to the lethal equivalents, the two-generation data provide separate information on the average intensity of mortality and the average number of deleterious genes carried by an individual. In our Markov chain Monte Carlo algorithm, we use a vector proposal distribution to overcome inefficiency of a single-site Gibbs sampler. Information about environmental effects is obtained from an outcrossing experiment conducted in parallel with the two-generation mating experiments.

  10. Separating multiple, short-term deleterious effects of saline solutions to the growth of cowpea seedlings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reductions in plant growth due to salinity are of global importance in natural and agricultural landscapes. Short-term (48 h) solution culture experiments studied 404 treatments with seedlings of cowpea (Vigna unguiculata (L.) Walp. cv. Caloona) to examine the multiple deleterious effects of Ca, Mg...

  11. Computational evaluation of cellular metabolic costs successfully predicts genes whose expression is deleterious

    PubMed Central

    Wagner, Allon; Zarecki, Raphy; Reshef, Leah; Gochev, Camelia; Sorek, Rotem; Gophna, Uri; Ruppin, Eytan

    2013-01-01

    Gene suppression and overexpression are both fundamental tools in linking genotype to phenotype in model organisms. Computational methods have proven invaluable in studying and predicting the deleterious effects of gene deletions, and yet parallel computational methods for overexpression are still lacking. Here, we present Expression-Dependent Gene Effects (EDGE), an in silico method that can predict the deleterious effects resulting from overexpression of either native or foreign metabolic genes. We first test and validate EDGE’s predictive power in bacteria through a combination of small-scale growth experiments that we performed and analysis of extant large-scale datasets. Second, a broad cross-species analysis, ranging from microorganisms to multiple plant and human tissues, shows that genes that EDGE predicts to be deleterious when overexpressed are indeed typically down-regulated. This reflects a universal selection force keeping the expression of potentially deleterious genes in check. Third, EDGE-based analysis shows that cancer genetic reprogramming specifically suppresses genes whose overexpression impedes proliferation. The magnitude of this suppression is large enough to enable an almost perfect distinction between normal and cancerous tissues based solely on EDGE results. We expect EDGE to advance our understanding of human pathologies associated with up-regulation of particular transcripts and to facilitate the utilization of gene overexpression in metabolic engineering. PMID:24198337

  12. Deleterious BRCA1/2 mutations in an urban population of Black women.

    PubMed

    Lynce, Filipa; Smith, Karen Lisa; Stein, Julie; DeMarco, Tiffani; Wang, Yiru; Wang, Hongkun; Fries, Melissa; Peshkin, Beth N; Isaacs, Claudine

    2015-08-01

    Information on the prevalence of deleterious BRCA1 and BRCA2 (BRCA1/2) mutations in clinic-based populations of Black women is limited. In order to address this gap, we performed a retrospective study to determine the prevalence of deleterious BRCA1/2 mutations, predictors of having a mutation, and acceptance of risk-reducing surgeries in Black women. In an urban unselected clinic-based population, we evaluated 211 self-identified Black women who underwent genetic counseling for hereditary breast-ovarian cancer syndrome. BRCA1/2 mutations were identified in 13.4% of the participants who received genetic testing. Younger age at diagnosis, higher BRCAPRO score, significant family history, and diagnosis of triple-negative breast cancer were associated with identification of a BRCA1/2 mutation. Of the affected patients found to have a deleterious mutation, almost half underwent prophylactic measures. In our study population, 1 in 7 Black women who underwent genetic testing harbored a deleterious BRCA1/2 mutation independent of age at diagnosis or family history.

  13. Recurrent loss of sex is associated with accumulation of deleterious mutations in Oenothera.

    PubMed

    Hollister, Jesse D; Greiner, Stephan; Wang, Wei; Wang, Jun; Zhang, Yong; Wong, Gane Ka-Shu; Wright, Stephen I; Johnson, Marc T J

    2015-04-01

    Sexual reproduction is nearly universal among eukaryotes. Theory predicts that the rarity of asexual eukaryotic species is in part caused by accumulation of deleterious mutations and heightened extinction risk associated with suppressed recombination and segregation in asexual species. We tested this prediction with a large data set of 62 transcriptomes from 29 species in the plant genus Oenothera, spanning ten independent transitions between sexual and a functionally asexual genetic system called permanent translocation heterozygosity. Illumina short-read sequencing and de novo transcript assembly yielded an average of 16.4 Mb of sequence per individual. Here, we show that functionally asexual species accumulate more deleterious mutations than sexual species using both population genomic and phylogenetic analysis. At an individual level, asexual species exhibited 1.8 × higher heterozygosity than sexual species. Within species, we detected a higher proportion of nonsynonymous polymorphism relative to synonymous variation within asexual compared with sexual species, indicating reduced efficacy of purifying selection. Asexual species also exhibited a greater proportion of transcripts with premature stop codons. The increased proportion of nonsynonymous mutations was also positively correlated with divergence time between sexual and asexual species, consistent with Muller's ratchet. Between species, we detected repeated increases in the ratio of nonsynonymous to synonymous divergence in asexual species compared with sexually reproducing sister taxa, indicating increased accumulation of deleterious mutations. These results confirm that an important advantage of sex is that it facilitates selection against deleterious alleles, which might help to explain the dearth of extant asexual species.

  14. Similarity of Deleterious Effects of Divorce on Chinese and American Children.

    ERIC Educational Resources Information Center

    Zhou, Zheng; Bray, Melissa A.; Kehle, Thomas J.; Xin, Tao

    2001-01-01

    Reviews and contrasts the effects of divorce on Chinese children's adjustment to American children of divorce. Results indicate that the deleterious effects of divorce on children's academic and social functioning appear to be similar to that experienced by American children. (Contains 23 references.) (GCP)

  15. Mating density and the strength of sexual selection against deleterious alleles in Drosophila melanogaster.

    PubMed

    Sharp, Nathaniel P; Agrawal, Aneil F

    2008-04-01

    Deleterious alleles constantly enter populations via mutation. Their presence reduces mean fitness and may threaten population persistence. It has been suggested that sexual selection may be an efficient way by which deleterious alleles are removed from populations but there is little direct experimental evidence. Because of its potential role in mutational meltdowns, there is particular interest in whether the strength of sexual selection changes with density. For each of eight visible markers in Drosophila melanogaster we have compared the strength of sexual selection at two densities. We find evidence of strong sexual selection against most but not all of these alleles. There is no evidence that sexual selection tends to be stronger (or weaker) at high density relative to low density. In addition, we also measure the effects of these mutations on two key parameters relevant to population productivity--juvenile viability and female fecundity. In most cases, sexual selection is as strong or stronger than these other forms of selection.

  16. Brief report: Labelling effects on the perceived deleterious consequences of pop music listening.

    PubMed

    North, Adrian C; Hargreaves, David J

    2005-06-01

    Several correlational studies have supported the claim of conservative protestors that there exists a positive relationship between listening to pop music and adolescent problem behaviours. However, research on the so-called 'prestige effects' has shown that experimental participants' responses to music can be mediated by manipulations of prior information concerning that music. This study investigated whether perceptions of deleterious effects of pop songs on listeners may be attributable to prior labelling of those stimuli as 'problem music'. Eighty undergraduates were played songs that they were told were either suicide-inducing or life-affirming. Subsequent ratings of the songs indicated that those presented as 'suicide-inducing' were perceived as such, whereas presentation of the same songs in a 'life-affirming' frame led to the perception of them as such. These findings indicate that censorship and the subsequent labelling of certain songs as 'problematic' might itself cause these songs to have deleterious effects on listeners.

  17. Brief report: Labelling effects on the perceived deleterious consequences of pop music listening.

    PubMed

    North, Adrian C; Hargreaves, David J

    2005-06-01

    Several correlational studies have supported the claim of conservative protestors that there exists a positive relationship between listening to pop music and adolescent problem behaviours. However, research on the so-called 'prestige effects' has shown that experimental participants' responses to music can be mediated by manipulations of prior information concerning that music. This study investigated whether perceptions of deleterious effects of pop songs on listeners may be attributable to prior labelling of those stimuli as 'problem music'. Eighty undergraduates were played songs that they were told were either suicide-inducing or life-affirming. Subsequent ratings of the songs indicated that those presented as 'suicide-inducing' were perceived as such, whereas presentation of the same songs in a 'life-affirming' frame led to the perception of them as such. These findings indicate that censorship and the subsequent labelling of certain songs as 'problematic' might itself cause these songs to have deleterious effects on listeners. PMID:15925693

  18. Modes of reproduction and the accumulation of deleterious mutations with multiplicative fitness effects.

    PubMed Central

    Haccou, Patsy; Schneider, Maria Victoria

    2004-01-01

    Mutational load depends not only on the number and nature of mutations but also on the reproductive mode. Traditionally, only a few specific reproductive modes are considered in the search of explanations for the maintenance of sex. There are, however, many alternatives. Including these may give radically different conclusions. The theory on deterministic deleterious mutations states that in large populations segregation and recombination may lead to a lower load of deleterious mutations, provided that there are synergistic interactions. Empirical research suggests that effects of deleterious mutations are often multiplicative. Such situations have largely been ignored in the literature, since recombination and segregation have no effect on mutation load in the absence of epistasis. However, this is true only when clonal reproduction and sexual reproduction with equal male and female ploidy are considered. We consider several alternative reproductive modes that are all known to occur in insects: arrhenotoky, paternal genome elimination, apomictic thelytoky, and automictic thelytoky with different cytological mechanisms to restore diploidy. We give a method that is based on probability-generating functions, which provides analytical and numerical results on the distributions of deleterious mutations. Using this, we show that segregation and recombination do make a difference. Furthermore, we prove that a modified form of Haldane's principle holds more generally for thelytokous reproduction. We discuss the implications of our results for evolutionary transitions between different reproductive modes in insects. Since the strength of Muller's ratchet is reduced considerably for several forms of automictic thelytoky, many of our results are expected to be also valid for initially small populations. PMID:15020489

  19. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies

    PubMed Central

    Dong, Chengliang; Wei, Peng; Jian, Xueqiu; Gibbs, Richard; Boerwinkle, Eric; Wang, Kai; Liu, Xiaoming

    2015-01-01

    Accurate deleteriousness prediction for nonsynonymous variants is crucial for distinguishing pathogenic mutations from background polymorphisms in whole exome sequencing (WES) studies. Although many deleteriousness prediction methods have been developed, their prediction results are sometimes inconsistent with each other and their relative merits are still unclear in practical applications. To address these issues, we comprehensively evaluated the predictive performance of 18 current deleteriousness-scoring methods, including 11 function prediction scores (PolyPhen-2, SIFT, MutationTaster, Mutation Assessor, FATHMM, LRT, PANTHER, PhD-SNP, SNAP, SNPs&GO and MutPred), 3 conservation scores (GERP++, SiPhy and PhyloP) and 4 ensemble scores (CADD, PON-P, KGGSeq and CONDEL). We found that FATHMM and KGGSeq had the highest discriminative power among independent scores and ensemble scores, respectively. Moreover, to ensure unbiased performance evaluation of these prediction scores, we manually collected three distinct testing datasets, on which no current prediction scores were tuned. In addition, we developed two new ensemble scores that integrate nine independent scores and allele frequency. Our scores achieved the highest discriminative power compared with all the deleteriousness prediction scores tested and showed low false-positive prediction rate for benign yet rare nonsynonymous variants, which demonstrated the value of combining information from multiple orthologous approaches. Finally, to facilitate variant prioritization in WES studies, we have pre-computed our ensemble scores for 87 347 044 possible variants in the whole-exome and made them publicly available through the ANNOVAR software and the dbNSFP database. PMID:25552646

  20. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies.

    PubMed

    Dong, Chengliang; Wei, Peng; Jian, Xueqiu; Gibbs, Richard; Boerwinkle, Eric; Wang, Kai; Liu, Xiaoming

    2015-04-15

    Accurate deleteriousness prediction for nonsynonymous variants is crucial for distinguishing pathogenic mutations from background polymorphisms in whole exome sequencing (WES) studies. Although many deleteriousness prediction methods have been developed, their prediction results are sometimes inconsistent with each other and their relative merits are still unclear in practical applications. To address these issues, we comprehensively evaluated the predictive performance of 18 current deleteriousness-scoring methods, including 11 function prediction scores (PolyPhen-2, SIFT, MutationTaster, Mutation Assessor, FATHMM, LRT, PANTHER, PhD-SNP, SNAP, SNPs&GO and MutPred), 3 conservation scores (GERP++, SiPhy and PhyloP) and 4 ensemble scores (CADD, PON-P, KGGSeq and CONDEL). We found that FATHMM and KGGSeq had the highest discriminative power among independent scores and ensemble scores, respectively. Moreover, to ensure unbiased performance evaluation of these prediction scores, we manually collected three distinct testing datasets, on which no current prediction scores were tuned. In addition, we developed two new ensemble scores that integrate nine independent scores and allele frequency. Our scores achieved the highest discriminative power compared with all the deleteriousness prediction scores tested and showed low false-positive prediction rate for benign yet rare nonsynonymous variants, which demonstrated the value of combining information from multiple orthologous approaches. Finally, to facilitate variant prioritization in WES studies, we have pre-computed our ensemble scores for 87 347 044 possible variants in the whole-exome and made them publicly available through the ANNOVAR software and the dbNSFP database. PMID:25552646

  1. The Evolution of Selfing Is Accompanied by Reduced Efficacy of Selection and Purging of Deleterious Mutations

    PubMed Central

    Arunkumar, Ramesh; Ness, Rob W.; Wright, Stephen I.; Barrett, Spencer C. H.

    2015-01-01

    The transition from outcrossing to selfing is predicted to reduce the genome-wide efficacy of selection because of the lower effective population size (Ne) that accompanies this change in mating system. However, strongly recessive deleterious mutations exposed in the homozygous backgrounds of selfers should be under strong purifying selection. Here, we examine estimates of the distribution of fitness effects (DFE) and changes in the magnitude of effective selection coefficients (Nes) acting on mutations during the transition from outcrossing to selfing. Using forward simulations, we investigated the ability of a DFE inference approach to detect the joint influence of mating system and the dominance of deleterious mutations on selection efficacy. We investigated predictions from our simulations in the annual plant Eichhornia paniculata, in which selfing has evolved from outcrossing on multiple occasions. We used range-wide sampling to generate population genomic datasets and identified nonsynonymous and synonymous polymorphisms segregating in outcrossing and selfing populations. We found that the transition to selfing was accompanied by a change in the DFE, with a larger fraction of effectively neutral sites (Nes < 1), a result consistent with the effects of reduced Ne in selfers. Moreover, an increased proportion of sites in selfers were under strong purifying selection (Nes > 100), and simulations suggest that this is due to the exposure of recessive deleterious mutations. We conclude that the transition to selfing has been accompanied by the genome-wide influences of reduced Ne and strong purifying selection against deleterious recessive mutations, an example of purging at the molecular level. PMID:25552275

  2. Sexual selection is ineffectual or inhibits the purging of deleterious mutations in Drosophila melanogaster.

    PubMed

    Arbuthnott, Devin; Rundle, Howard D

    2012-07-01

    The effects of sexual selection on population mean fitness are unclear and a subject of debate. Recent models propose that, because reproductive success may be condition dependent, much of the genome may be a target of sexual selection. Under this scenario, mutations that reduce health, and thus nonsexual fitness, may also be deleterious with respect to reproductive success, meaning that sexual selection may contribute to the purging of deleterious alleles. We tested this hypothesis directly by subjecting replicate Drosophila melanogaster populations to two treatments that altered the opportunity for sexual selection and then tracked changes in the frequency of six separate deleterious alleles with recessive and visible phenotypic effects. While natural selection acted to decrease the frequency of all six mutations, the addition of sexual selection did not aid in the purging of any of them, and for three of them appears to have hampered it. Courtship and mating have harmful effects in this species and mate choice assays showed that males directed more courtship and mating behavior toward wild-type over mutant females, providing a likely explanation for sexual selection's cost. Whether this cost extends to other mutations (e.g., those lacking visible phenotypic effects) is an important topic for future research.

  3. Somatic deleterious mutation rate in a woody plant: estimation from phenotypic data

    PubMed Central

    Bobiwash, K; Schultz, S T; Schoen, D J

    2013-01-01

    We conducted controlled crosses in populations of the long-lived clonal shrub, Vaccinium angustifolium (lowbush blueberry) to estimate inbreeding depression and mutation parameters associated with somatic deleterious mutation. Inbreeding depression level was high, with many plants failing to set fruit after self-pollination. We also compared fruit set from autogamous pollinations (pollen collected from within the same inflorescence) with fruit set from geitonogamous pollinations (pollen collected from the same plant but from inflorescences separated by several meters of branch growth). The difference between geitonogamous versus autogamous fitness within single plants is referred to as ‘autogamy depression' (AD). AD can be caused by somatic deleterious mutation. AD was significantly different from zero for fruit set. We developed a maximum-likelihood procedure to estimate somatic mutation parameters from AD, and applied it to geitonogamous and autogamous fruit set data from this experiment. We infer that, on average, approximately three sublethal, partially dominant somatic mutations exist within the crowns of the plants studied. We conclude that somatic mutation in this woody plant results in an overall genomic deleterious mutation rate that exceeds the rate measured to date for annual plants. Some implications of this result for evolutionary biology and agriculture are discussed. PMID:23778990

  4. The evolution of XY recombination: sexually antagonistic selection versus deleterious mutation load.

    PubMed

    Grossen, Christine; Neuenschwander, Samuel; Perrin, Nicolas

    2012-10-01

    Recombination arrest between X and Y chromosomes, driven by sexually antagonistic genes, is expected to induce their progressive differentiation. However, in contrast to birds and mammals (which display the predicted pattern), most cold-blooded vertebrates have homomorphic sex chromosomes. Two main hypotheses have been proposed to account for this, namely high turnover rates of sex-determining systems and occasional XY recombination. Using individual-based simulations, we formalize the evolution of XY recombination (here mediated by sex reversal; the "fountain-of-youth" model) under the contrasting forces of sexually antagonistic selection and deleterious mutations. The shift between the domains of elimination and accumulation occurs at much lower selection coefficients for the Y than for the X. In the absence of dosage compensation, mildly deleterious mutations accumulating on the Y depress male fitness, thereby providing incentives for XY recombination. Under our settings, this occurs via "demasculinization" of the Y, allowing recombination in XY (sex-reversed) females. As we also show, this generates a conflict with the X, which coevolves to oppose sex reversal. The resulting rare events of XY sex reversal are enough to purge the Y from its load of deleterious mutations. Our results support the "fountain of youth" as a plausible mechanism to account for the maintenance of sex-chromosome homomorphy. PMID:23025605

  5. A perspective on the evolution of germ-cell development and germinal mosaics of deleterious mutations.

    PubMed

    Woodruff, Ronny C; Balinski, Michael A; Bouzat, Juan L

    2015-10-01

    In many animals a small number of primordial germ cells (PGCs) are set aside early in development, mitosis and mitochondrial DNA syntheses are arrested, transcription is stopped or reduced, and the PGCs migrate later to the emerging gonads and become germ cells. What could be the evolutionary advantage of sequestering non-dividing PGCs early in development? A commonly cited advantage is a reduction in the number of new deleterious mutations that would occur if there were additional divisions in PGCs early in development. We would like to add to this advantage the fact that these additional mutations in PGCs give rise to germinal mosaics (i.e., premeiotic clusters of mutation) in multiple progeny of the same individual, thus having a larger detrimental effect on the evolutionary fitness of their carriers. Here, we reviewed published studies providing evidence that germinal mosaics of deleterious mutant alleles are not rare, occur for all types of genetic damage, and have been observed in all tested organisms and in nature. We propose the hypothesis that PGC sequestration during early animal development may have evolved in part in response to selection for preventing the occurrence of premeiotic clusters of deleterious mutant alleles, and describe a series of predictions that would allow the assessment of the potential role of germinal mosaics on the evolution of PGC sequestration.

  6. Deleterious mutations and the genetic variance of male fitness components in Mimulus guttatus.

    PubMed Central

    Kelly, John K

    2003-01-01

    Deleterious mutations are relevant to a broad range of questions in genetics and evolutionary biology. I present an application of the "biometric method" for estimating mutational parameters for male fitness characters of the yellow monkeyflower, Mimulus guttatus. The biometric method rests on two critical assumptions. The first is that experimental inbreeding changes genotype frequencies without changing allele frequencies; i.e., there is no genetic purging during the experiment. I satisfy this condition by employing a breeding design in which the parents are randomly extracted, fully homozygous inbred lines. The second is that all genetic variation is attributable to deleterious mutations maintained in mutation-selection balance. I explicitly test this hypothesis using likelihood ratios. Of the three deleterious mutation models tested, the first two are rejected for all characters. The failure of these models is due to an excess of additive genetic variation relative to the expectation under mutation-selection balance. The third model is not rejected for either of two log-transformed male fitness traits. However, this model imposes only "weak conditions" and is not sufficiently detailed to provide estimates for mutational parameters. The implication is that, if biometric methods are going to yield useful parameter estimates, they will need to consider mutational models more complicated than those typically employed in experimental studies. PMID:12871916

  7. Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes

    PubMed Central

    Chen, Xin; Guo, Jun; Cai, Tao; Zhang, Fengshan; Pan, Shengfa; Zhang, Li; Wang, Shaobo; Zhou, Feifei; Diao, Yinze; Zhao, Yanbin; Chen, Zhen; Liu, Xiaoguang; Chen, Zhongqiang; Liu, Zhongjun; Sun, Yu; Du, Jie

    2016-01-01

    Ossification of the posterior longitudinal ligament of the spine (OPLL), which is characterized by ectopic bone formation in the spinal ligaments, can cause spinal-cord compression. To date, at least 11 susceptibility genes have been genetically linked to OPLL. In order to identify potential deleterious alleles in these OPLL-associated genes, we designed a capture array encompassing all coding regions of the target genes for next-generation sequencing (NGS) in a cohort of 55 unrelated patients with OPLL. By bioinformatics analyses, we successfully identified three novel and five extremely rare variants (MAF < 0.005). These variants were predicted to be deleterious by commonly used various algorithms, thereby resulting in missense mutations in four OPLL-associated genes (i.e., COL6A1, COL11A2, FGFR1, and BMP2). Furthermore, potential effects of the patient with p.Q89E of BMP2 were confirmed by a markedly increased BMP2 level in peripheral blood samples. Notably, seven of the variants were found to be associated with the patients with continuous subtype changes by cervical spinal radiological analyses. Taken together, our findings revealed for the first time that deleterious coding variants of the four OPLL-associated genes are potentially pathogenic in the patients with OPLL. PMID:27246988

  8. [Reduction of a risk of the deleterious effects of persistent toxic substances on the health of the far north population].

    PubMed

    Dudarev, A A; Mizerniuk, V N; Chupakhin, V S; Lebedev, G B; Chashchin, V P

    2010-01-01

    The paper presents the general principles and procedure of the development and implementation of measures to decrease and prevent environmental pollution with persistent toxic substances (PTS) in the Russian Arctic and, accordingly, to reduce a risk of the deleterious effects of PTS on human health. Based on the results of a study of PTS in the Russian Arctic (from the Kola Peninsula to Chukotka), the authors first systematized the basic lines and actions and formulated specific measures to reduce the North population's exposure to PTSs, such as polychlorinated biphenyls, organic chlorine pesticides (dichlorodiphenyltrichloroethane, hexachlorocyclohexane, hexachlorobenzene, etc.), and heavy metals (mercury, lead, cadmium). A package of measures is aimed at maximally reducing the presence of PTS-containing objects and materials in the north (via detection, collection, and extermination), at neutralizing the soils in settlement lands, at setting up safe water consumption systems, at organizing effective control over the safe use of chemicals and the levels of PTS in raw food materials and foodstuffs, and at working out recommendations on safe procedures for food purchase, storage, and cooking. PMID:20491265

  9. Can Platelet-Rich Plasma Protect Rat Achilles Tendons From the Deleterious Effects of Triamcinolone Acetonide?

    PubMed Central

    Muto, Tomoyuki; Kokubu, Takeshi; Mifune, Yutaka; Inui, Atsuyuki; Sakata, Ryosuke; Harada, Yoshifumi; Takase, Fumiaki; Ueda, Yasuhiro; Kuroda, Ryosuke; Kurosaka, Masahiro

    2015-01-01

    Background Triamcinolone acetonide (TA) injections are widely used for tendinitis but have deleterious effects, including tendon degeneration or tendon rupture. Purpose To investigate whether adding platelet-rich plasma (PRP), a blood fraction that participates in tissue repair processes, to TA can prevent its deleterious effects. Study Design Controlled laboratory study. Methods Rat Achilles tendons were injected with TA, TA + PRP, PRP alone, or saline (control). Biomechanical testing and histological analyses were performed on Achilles tendons 1 week after injections. Results The maximum failure loads in the control, TA, TA + PRP, and PRP groups were 31.7 ± 2.3, 19.0 ± 3.6, 31.0 ± 7.1, and 30.2 ± 6.8 N, respectively. The tendon stiffness in the control, TA, TA + PRP, and PRP groups was 12.1 ± 1.8, 7.5 ± 1.8, 11.0 ± 2.8, and 11.3 ± 2.5 N/mm, respectively. The maximum failure load and stiffness were significantly lower in the TA group compared with the other 3 groups. There was no significant difference between the TA + PRP and control groups. Cell invasions, vacuolation, collagen attenuation, and increased type III collagen expression were histologically observed in the TA group; however, these changes were prevented by the simultaneous administration of PRP. Conclusion Administering PRP may prevent deleterious effects caused by TA; therefore, PRP may be used as a protective agent in clinical situations. Clinical Relevance PRP can be useful as a protective agent for sports injury patients receiving local corticosteroid injections. PMID:26673355

  10. SDS, a structural disruption score for assessment of missense variant deleteriousness

    PubMed Central

    Preeprem, Thanawadee; Gibson, Greg

    2014-01-01

    We have developed a novel structure-based evaluation for missense variants that explicitly models protein structure and amino acid properties to predict the likelihood that a variant disrupts protein function. A structural disruption score (SDS) is introduced as a measure to depict the likelihood that a case variant is functional. The score is constructed using characteristics that distinguish between causal and neutral variants within a group of proteins. The SDS score is correlated with standard sequence-based deleteriousness, but shows promise for improving discrimination between neutral and causal variants at less conserved sites. The prediction was performed on 3-dimentional structures of 57 gene products whose homozygous SNPs were identified as case-exclusive variants in an exome sequencing study of epilepsy disorders. We contrasted the candidate epilepsy variants with scores for likely benign variants found in the EVS database, and for positive control variants in the same genes that are suspected to promote a range of diseases. To derive a characteristic profile of damaging SNPs, we transformed continuous scores into categorical variables based on the score distribution of each measurement, collected from all possible SNPs in this protein set, where extreme measures were assumed to be deleterious. A second epilepsy dataset was used to replicate the findings. Causal variants tend to receive higher sequence-based deleterious scores, induce larger physico-chemical changes between amino acid pairs, locate in protein domains, buried sites or on conserved protein surface clusters, and cause protein destabilization, relative to negative controls. These measures were agglomerated for each variant. A list of nine high-priority putative functional variants for epilepsy was generated. Our newly developed SDS protocol facilitates SNP prioritization for experimental validation. PMID:24795746

  11. Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia

    PubMed Central

    Yu, Lan; Sawle, Ashley D.; Wynn, Julia; Aspelund, Gudrun; Stolar, Charles J.; Arkovitz, Marc S.; Potoka, Douglas; Azarow, Kenneth S.; Mychaliska, George B.; Shen, Yufeng; Chung, Wendy K.

    2015-01-01

    Congenital diaphragmatic hernia (CDH) is a serious birth defect that accounts for 8% of all major birth anomalies. Approximately 40% of cases occur in association with other anomalies. As sporadic complex CDH likely has a significant impact on reproductive fitness, we hypothesized that de novo variants would account for the etiology in a significant fraction of cases. We performed exome sequencing in 39 CDH trios and compared the frequency of de novo variants with 787 unaffected controls from the Simons Simplex Collection. We found no significant difference in overall frequency of de novo variants between cases and controls. However, among genes that are highly expressed during diaphragm development, there was a significant burden of likely gene disrupting (LGD) and predicted deleterious missense variants in cases (fold enrichment = 3.2, P-value = 0.003), and these genes are more likely to be haploinsufficient (P-value = 0.01) than the ones with benign missense or synonymous de novo variants in cases. After accounting for the frequency of de novo variants in the control population, we estimate that 15% of sporadic complex CDH patients are attributable to de novo LGD or deleterious missense variants. We identified several genes with predicted deleterious de novo variants that fall into common categories of genes related to transcription factors and cell migration that we believe are related to the pathogenesis of CDH. These data provide supportive evidence for novel genes in the pathogenesis of CDH associated with other anomalies and suggest that de novo variants play a significant role in complex CDH cases. PMID:26034137

  12. Effects of chronic hypergravity: from adaptive to deleterious responses in growing mouse skeleton.

    PubMed

    Gnyubkin, Vasily; Guignandon, Alain; Laroche, Norbert; Vanden-Bossche, Arnaud; Normand, Myriam; Lafage-Proust, Marie-Hélène; Vico, Laurence

    2015-10-15

    One of the most important but least studied environmental factors playing a major role in bone physiology is gravity. While the knowledge of deleterious effects of microgravity on the skeleton is expanding, little is known about hypergravity and its osteogenic potential. Centrifugation was used to assess effects of 21-day continuous 2- or 3-g acceleration on femur and L2-vertebra of 7-wk-old male C57BL/6 mice. Under 3 g, body mass growth slowed down, and deleterious skeletal effects were found (P < 0.05 compared with control): cortical thinning, osteoclasts surface increase (+41% in femur, +20% in vertebra), and bone formation rate decrease (-34% in femur, -38% in vertebra). A 2-g centrifugation did not reduce body mass and improved trabecular volume (+18% in femur, +13% in vertebra) and microarchitecture (+32% connectivity density in femur, +9% trabecular thickness in vertebra, P < 0.05 compared with control). Centrifugation at 2 g also decreased osteoclast surfaces (-36% in femur, -16% in vertebra) and increased the extent of mineralized surfaces (+31% in femur, +48% in vertebra, P < 0.05 compare to control). Quantitative immunohistochemistry revealed an increase of dentin matrix acidic phosphoprotein 1 (DMP1) and decrease of sclerostin (+60% and -35% respectively, P < 0.001 compared with control) in the femur cortex of 2-g mice. In the distal femur metaphysis, the number and volume of blood vessels increased by 22 and 44%, respectively (P < 0.05 compared with control). In conclusion, the effects of continuous hypergravity were bone compartment-specific and depended on the gravity level, with a threshold between beneficial 2-g and deleterious 3-g effects.

  13. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.

    PubMed

    Bedarida, Tatiana; Baron, Stephanie; Vessieres, Emilie; Vibert, Francoise; Ayer, Audrey; Marchiol-Fournigault, Carmen; Henrion, Daniel; Paul, Jean-Louis; Noble, Florence; Golmard, Jean-Louis; Beaudeux, Jean-Louis; Cottart, Charles-Henry; Nivet-Antoine, Valerie

    2014-09-01

    High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet.

  14. Analysis of the estimators of the average coefficient of dominance of deleterious mutations.

    PubMed

    Fernández, B; García-Dorado, A; Caballero, A

    2004-10-01

    We investigate the sources of bias that affect the most commonly used methods of estimation of the average degree of dominance (h) of deleterious mutations, focusing on estimates from segregating populations. The main emphasis is on the effect of the finite size of the populations, but other sources of bias are also considered. Using diffusion approximations to the distribution of gene frequencies in finite populations as well as stochastic simulations, we assess the behavior of the estimators obtained from populations at mutation-selection-drift balance under different mutational scenarios and compare averages of h for newly arisen and segregating mutations. Because of genetic drift, the inferences concerning newly arisen mutations based on the mutation-selection balance theory can have substantial upward bias depending upon the distribution of h. In addition, estimates usually refer to h weighted by the homozygous deleterious effect in different ways, so that inferences are complicated when these two variables are negatively correlated. Due to both sources of bias, the widely used regression of heterozygous on homozygous means underestimates the arithmetic mean of h for segregating mutations, in contrast to their repeatedly assumed equality in the literature. We conclude that none of the estimators from segregating populations provides, under general conditions, a useful tool to ascertain the properties of the degree of dominance, either for segregating or for newly arisen deleterious mutations. Direct estimates of the average h from mutation-accumulation experiments are shown to suffer some bias caused by purging selection but, because they do not require assumptions on the causes maintaining segregating variation, they appear to give a more reliable average dominance for newly arisen mutations.

  15. One-Nanometer Thin Monolayers Remove the Deleterious Effect of Substrate Defects in Molecular Tunnel Junctions.

    PubMed

    Jiang, Li; Sangeeth, C S Suchand; Yuan, Li; Thompson, Damien; Nijhuis, Christian A

    2015-10-14

    Defects in self-assembled monolayer (SAMs) based junctions cause the largest deviation between predicted and measured values of the tunnelling current. We report the remarkable, seemingly counterintuitive finding that shorter, less-ordered SAMs provide, unlike taller crystalline-like SAMs, higher quality tunnelling barriers on defective substrates, which points to self-repair of liquid-like SAMs on defects. The molecular dynamics show that short-chain molecules can more easily rotate into low-density boundary regions and smoothen out defects than thick solid-like SAMs. Our findings point to an attractive means of removing their deleterious effects simply by using flexible molecules.

  16. Deleterious effects of recombination and possible nonrecombinatorial advantages of sex in a fungal model.

    PubMed

    López-Villavicencio, M; Debets, A J M; Slakhorst, M; Giraud, T; Schoustra, S E

    2013-09-01

    Why sexual reproduction is so prevalent in nature remains a major question in evolutionary biology. Most of the proposed advantages of sex rely on the benefits obtained from recombination. However, it is still unclear whether the conditions under which these recombinatorial benefits would be sufficient to maintain sex in the short term are met in nature. Our study addresses a largely overlooked hypothesis, proposing that sex could be maintained in the short term by advantages due to functions linked with sex, but not related to recombination. These advantages would be so essential that sex could not be lost in the short term. Here, we used the fungus Aspergillus nidulans to experimentally test predictions of this hypothesis. Specifically, we were interested in (i) the short-term deleterious effects of recombination, (ii) possible nonrecombinatorial advantages of sex particularly through the elimination of mutations and (iii) the outcrossing rate under choice conditions in a haploid fungus able to reproduce by both outcrossing and haploid selfing. Our results were consistent with our hypotheses: we found that (i) recombination can be strongly deleterious in the short term, (ii) sexual reproduction between individuals derived from the same clonal lineage provided nonrecombinatorial advantages, likely through a selection arena mechanism, and (iii) under choice conditions, outcrossing occurs in a homothallic species, although at low rates.

  17. Accumulation of Deleterious Passenger Mutations Is Associated with the Progression of Hepatocellular Carcinoma.

    PubMed

    Budzinska, Magdalena A; Tu, Thomas; d'Avigdor, William M H; McCaughan, Geoffrey W; Luciani, Fabio; Shackel, Nicholas A

    2016-01-01

    In hepatocellular carcinoma (HCC), somatic genome-wide DNA mutations are numerous, universal and heterogeneous. Some of these somatic mutations are drivers of the malignant process but the vast majority are passenger mutations. These passenger mutations can be deleterious to individual protein function but are tolerated by the cell or are offset by a survival advantage conferred by driver mutations. It is unknown if these somatic deleterious passenger mutations (DPMs) develop in the precancerous state of cirrhosis or if it is confined to HCC. Therefore, we studied four whole-exome sequencing datasets, including patients with non-cirrhotic liver (n = 12), cirrhosis without HCC (n = 6) and paired HCC with surrounding non-HCC liver (n = 74 paired samples), to identify DPMs. After filtering out putative germline mutations, we identified 187±22 DPMs per non-diseased tissue. DPMs number was associated with liver disease progressing to HCC, independent of the number of exonic mutations. Tumours contained significantly more DPMs compared to paired non-tumour tissue (258-293 per HCC exome). Cirrhosis- and HCC-associated DPMs do not occur predominantly in specific genes, chromosomes or biological pathways and the effect on tumour biology is presently unknown. Importantly, for the first time we have shown a significant increase in DPMs with HCC. PMID:27631787

  18. Accumulation of Deleterious Passenger Mutations Is Associated with the Progression of Hepatocellular Carcinoma

    PubMed Central

    d’Avigdor, William M. H.; McCaughan, Geoffrey W.; Luciani, Fabio; Shackel, Nicholas A.

    2016-01-01

    In hepatocellular carcinoma (HCC), somatic genome-wide DNA mutations are numerous, universal and heterogeneous. Some of these somatic mutations are drivers of the malignant process but the vast majority are passenger mutations. These passenger mutations can be deleterious to individual protein function but are tolerated by the cell or are offset by a survival advantage conferred by driver mutations. It is unknown if these somatic deleterious passenger mutations (DPMs) develop in the precancerous state of cirrhosis or if it is confined to HCC. Therefore, we studied four whole-exome sequencing datasets, including patients with non-cirrhotic liver (n = 12), cirrhosis without HCC (n = 6) and paired HCC with surrounding non-HCC liver (n = 74 paired samples), to identify DPMs. After filtering out putative germline mutations, we identified 187±22 DPMs per non-diseased tissue. DPMs number was associated with liver disease progressing to HCC, independent of the number of exonic mutations. Tumours contained significantly more DPMs compared to paired non-tumour tissue (258–293 per HCC exome). Cirrhosis- and HCC-associated DPMs do not occur predominantly in specific genes, chromosomes or biological pathways and the effect on tumour biology is presently unknown. Importantly, for the first time we have shown a significant increase in DPMs with HCC. PMID:27631787

  19. Accumulation of slightly deleterious mutations in mitochondrial protein-coding genes of large versus small mammals

    PubMed Central

    Popadin, Konstantin; Polishchuk, Leonard V.; Mamirova, Leila; Knorre, Dmitry; Gunbin, Konstantin

    2007-01-01

    After the effective size of a population, Ne, declines, some slightly deleterious amino acid replacements which were initially suppressed by purifying selection become effectively neutral and can reach fixation. Here we investigate this phenomenon for a set of all 13 mitochondrial protein-coding genes from 110 mammalian species. By using body mass as a proxy for Ne, we show that large mammals (i.e., those with low Ne) as compared with small ones (in our sample these are, on average, 369.5 kg and 275 g, respectively) have a 43% higher rate of accumulation of nonsynonymous nucleotide substitutions relative to synonymous substitutions, and an 8–40% higher rate of accumulation of radical amino acid substitutions relative to conservative substitutions, depending on the type of amino acid classification. These higher rates result in a 6% greater amino acid dissimilarity between modern species and their most recent reconstructed ancestors in large versus small mammals. Because nonsynonymous substitutions are likely to be more harmful than synonymous substitutions, and radical amino acid substitutions are likely to be more harmful than conservative ones, our results suggest that large mammals experience less efficient purifying selection than small mammals. Furthermore, because in the course of mammalian evolution body size tends to increase and, consequently, Ne tends to decline, evolution of mammals toward large body size may involve accumulation of slightly deleterious mutations in mitochondrial protein-coding genes, which may contribute to decline or extinction of large mammals. PMID:17679693

  20. Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer

    PubMed Central

    de Voer, Richarda M.; Hahn, Marc-Manuel; Mensenkamp, Arjen R.; Hoischen, Alexander; Gilissen, Christian; Henkes, Arjen; Spruijt, Liesbeth; van Zelst-Stams, Wendy A.; Marleen Kets, C.; Verwiel, Eugene T.; Nagtegaal, Iris D.; Schackert, Hans K.; van Kessel, Ad Geurts; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J.L.; Kuiper, Roland P.

    2015-01-01

    Bloom syndrome is an autosomal recessive disorder characterized by chromosomal instability and increased cancer risk, caused by biallelic mutations in the RECQL-helicase gene BLM. Previous studies have led to conflicting conclusions as to whether carriers of heterozygous BLM mutations have an increased risk to develop colorectal cancer (CRC). We recently identified two carriers of a pathogenic BLM mutation in a cohort of 55 early-onset CRC patients (≤45 years of age), suggesting an overrepresentation compared to the normal population. Here, we performed targeted sequencing using molecular inversion probes to screen an additional cohort of 185 CRC patients (≤50 years of age) and 532 population-matched controls for deleterious BLM mutations. In total, we identified three additional CRC patients (1.6%) and one control individual (0.2%) that carried a known pathogenic BLM mutation, suggesting that these mutations are enriched in early-onset CRC patients (P = 0.05516). A comparison with local and publically available databases from individuals without suspicion for hereditary cancer confirmed this enrichment (P = 0.003534). Analysis of family members of the five BLM mutation carriers with CRC suggests an incomplete penetrance for CRC development. Therefore, these data indicate that carriers of deleterious BLM mutations are at increased risk to develop CRC, albeit with a moderate-to-low penetrance. PMID:26358404

  1. In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene

    PubMed Central

    AbdulAzeez, Sayed; Borgio, J. Francis

    2016-01-01

    Background α-Thalassemia (α-thal) is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes. Method Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted. Results and Discussion A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs), 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3′ UTR SNPs, 9 coding synonymous SNPs, 9 5′ UTR SNPs and other types. Structural homology-based method (PolyPhen) and sequence homology-based tool (SIFT), SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic. Conclusions A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R) were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in-silico analysis that, two nsSNPs such as G60Vand W15R in HBA1 are highly deleterious. These “2 pathogenic nsSNPs” can be considered for wet-lab confirmatory analysis. PMID:26824843

  2. Genetic contribution to aging: deleterious and helpful genes define life expectancy.

    PubMed

    Lao, J I; Montoriol, C; Morer, I; Beyer, K

    2005-12-01

    For the best understanding of aging, we must consider a genetic pool in which genes with negative effects (deleterious genes that shorten the life span) interact with genes with positive effects (helpful genes that promote longevity) in a constant epistatic relationship that results in a modulation of the final expression under particular environmental influences. Examples of deleterious genes affecting aging (predisposition to early-life pathology and disease) are those that confer risk for developing vascular disease in the heart, brain, or peripheral vessels (APOE, ACE, MTFHR, and mutation at factor II and factor V genes), a gene associated with sporadic late-onset Alzheimer's disease (APOE E4), a polymorphism (COLIA1 Sp1) associated with an increased fracture risk, and several genetic polymorphisms involved in hormonal metabolism that affect adverse reactions to estrogen replacement in postmenopausal women. In summary, the process of aging can be regarded as a multifactorial trait that results from an interaction between stochastic events and sets of epistatic alleles that have pleiotropic age-dependent effects. Lacking those alleles that predispose to disease and having the longevity-enabling genes (those beneficial genetic variants that confer disease resistance) are probably both important to such a remarkable survival advantage.

  3. Rare deleterious mutations of the gene EFR3A in autism spectrum disorders

    PubMed Central

    2014-01-01

    Background Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. Methods We conducted a large case/control association study by deep resequencing and analysis of whole-exome data for coding and splice site variants in EFR3A. We determined the potential impact of these variants on protein structure and function by a variety of conservation measures and analysis of the Saccharomyces cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of EFR3A in human brain tissue. Results Rare nonsynonymous mutations in EFR3A were more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 = 0.35%) and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P = 0.0077, permutation test). Crystal structure analysis revealed that mutations likely to be deleterious were also statistically more common in cases than controls (P = 0.017, Fisher exact test). Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons, during human fetal brain development in a pattern consistent with ASD-related genes, and it is strongly co-expressed (P < 2.2 × 10−16, Wilcoxon test) with a module of genes significantly associated with ASD. Conclusions Rare deleterious mutations in EFR3A were found to be associated with ASD using an experiment-wide significance threshold. Synaptic phosphoinositide metabolism has been strongly implicated in syndromic forms of ASD. These data for EFR3A strengthen the evidence for the involvement of this pathway in idiopathic autism. PMID:24860643

  4. Exopolysaccharides protect Synechocystis against the deleterious effects of titanium dioxide nanoparticles in natural and artificial waters.

    PubMed

    Planchon, Mariane; Jittawuttipoka, Thichakorn; Cassier-Chauvat, Corinne; Guyot, François; Gelabert, Alexandre; Benedetti, Marc F; Chauvat, Franck; Spalla, Olivier

    2013-09-01

    We have studied the effect of TiO2 nanoparticles (NPs) on the model cyanobacteria Synechocystis PCC6803. We used well-characterized NPs suspensions in artificial and natural (Seine River, France) waters. We report that NPs trigger direct (cell killing) and indirect (cell sedimentation precluding the capture of light, which is crucial to photosynthesis) deleterious effects. Both toxic effects increase with NPs concentration and are exacerbated by the presence of UVAs that increase the production of Reactive Oxygen Species (hydroxyl and superoxide radicals) by TiO2 NPs. Furthermore, we compared the responses of the wild-type strain of Synechocystis, which possesses abundant exopolysaccharides surrounding the cells, to that of an EPS-depleted mutant. We show, for the first time, that the exopolysaccharides play a crucial role in Synechocystis protection against cell killing caused by TiO2 NPs.

  5. Deleterious Effects of Exact Exchange Functionals on Predictions of Molecular Conductance.

    PubMed

    Feng, Qingguo; Yamada, Atsushi; Baer, Roi; Dunietz, Barry D

    2016-08-01

    Kohn-Sham (KS) density functional theory (DFT) describes well the atomistic structure of molecular junctions and their coupling to the semi-infinite metallic electrodes but severely overestimates conductance due to the spuriously large density of charge-carrier states of the KS system. Previous works show that inclusion of appropriate amounts of nonlocal exchange in the functional can fix the problem and provide realistic conductance estimates. Here however we discover that nonlocal exchange can also lead to deleterious effects which artificially overestimate transmittance even beyond the KS-DFT prediction. The effect is a result of exchange coupling between nonoverlapping states of diradical character. We prescribe a practical recipe for eliminating such artifacts. PMID:27454778

  6. Genome-wide burden of deleterious coding variants increased in schizophrenia

    PubMed Central

    Loohuis, Loes M. Olde; Vorstman, Jacob A. S.; Ori, Anil P.; Staats, Kim A.; Wang, Tina; Richards, Alexander L.; Leonenko, Ganna; Walters, James T.; DeYoung, Joseph; Kahn, René S.; Linszen, Don; Os, Jim van; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Haan, Lieuwe de; Krabbendam, Lydia; Myin-Germeys, Inez; Cantor, Rita M.; Ophoff, Roel A.

    2015-01-01

    Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, schizophrenia cases carry an increased burden of deleterious mutations. At a genome-wide level, our results implicate non-synonymous, splice site as well as stop-altering single-nucleotide variations occurring at minor allele frequency of ≥0.01% in the population. In an independent replication sample of 5,585 schizophrenia cases and 8,103 controls of European ancestry we confirm an enrichment in cases of the alleles identified in our study. In addition, the genes implicated by the increased burden of rare coding variants highlight the involvement of neurodevelopment in the aetiology of schizophrenia. PMID:26158538

  7. Tipping the mutation-selection balance: Limited migration increases the frequency of deleterious mutants.

    PubMed

    Cooper, Jacob D; Neuhauser, Claudia; Dean, Antony M; Kerr, Benjamin

    2015-09-01

    Typical mutation-selection models assume well-mixed populations, but dispersal and migration within many natural populations is spatially limited. Such limitations can lead to enhanced variation among locations as different types become clustered in different places. Such clustering weakens competition between unlike types relative to competition between like types; thus, the rate by which a fitter type displaces an inferior competitor can be affected by the spatial scale of movement. In this paper, we use a birth-death model to show that limited migration can affect asexual populations by creating competitive refugia. We use a moment closure approach to show that as population structure is introduced by limiting migration, the equilibrial frequency of deleterious mutants increases. We support and extend the model through stochastic simulation, and we use a spatially explicit cellular automaton approach to corroborate the results. We discuss the implications of these results for standing variation in structured populations and adaptive valley crossing in Wright's "shifting balance" process.

  8. Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.

    PubMed

    Lin, Yi-Fan; Schulz, Anna M; Pellegrino, Mark W; Lu, Yun; Shaham, Shai; Haynes, Cole M

    2016-05-19

    Mitochondrial genomes (mitochondrial DNA, mtDNA) encode essential oxidative phosphorylation (OXPHOS) components. Because hundreds of mtDNAs exist per cell, a deletion in a single mtDNA has little impact. However, if the deletion genome is enriched, OXPHOS declines, resulting in cellular dysfunction. For example, Kearns-Sayre syndrome is caused by a single heteroplasmic mtDNA deletion. More broadly, mtDNA deletion accumulation has been observed in individual muscle cells and dopaminergic neurons during ageing. It is unclear how mtDNA deletions are tolerated or how they are propagated in somatic cells. One mechanism by which cells respond to OXPHOS dysfunction is by activating the mitochondrial unfolded protein response (UPR(mt)), a transcriptional response mediated by the transcription factor ATFS-1 that promotes the recovery and regeneration of defective mitochondria. Here we investigate the role of ATFS-1 in the maintenance and propagation of a deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain that stably expresses wild-type mtDNA and mtDNA with a 3.1-kilobase deletion (∆mtDNA) lacking four essential genes. The heteroplasmic strain, which has 60% ∆mtDNA, displays modest mitochondrial dysfunction and constitutive UPR(mt) activation. ATFS-1 impairment reduced the ∆mtDNA nearly tenfold, decreasing the total percentage to 7%. We propose that in the context of mtDNA heteroplasmy, UPR(mt) activation caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics. PMID:27135930

  9. Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning.

    PubMed

    Zubedat, Salman; Aga-Mizrachi, Shlomit; Cymerblit-Sabba, Adi; Ritter, Ami; Nachmani, Maayan; Avital, Avi

    2015-01-01

    Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

  10. Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy

    PubMed Central

    Leu, Costin; Balestrini, Simona; Maher, Bridget; Hernández-Hernández, Laura; Gormley, Padhraig; Hämäläinen, Eija; Heggeli, Kristin; Schoeler, Natasha; Novy, Jan; Willis, Joseph; Plagnol, Vincent; Ellis, Rachael; Reavey, Eleanor; O'Regan, Mary; Pickrell, William O.; Thomas, Rhys H.; Chung, Seo-Kyung; Delanty, Norman; McMahon, Jacinta M.; Malone, Stephen; Sadleir, Lynette G.; Berkovic, Samuel F.; Nashef, Lina; Zuberi, Sameer M.; Rees, Mark I.; Cavalleri, Gianpiero L.; Sander, Josemir W.; Hughes, Elaine; Helen Cross, J.; Scheffer, Ingrid E.; Palotie, Aarno; Sisodiya, Sanjay M.

    2015-01-01

    Sudden unexpected death in epilepsy (SUDEP) represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls. Association analysis revealed a significantly increased genome-wide polygenic burden per individual in the SUDEP cohort when compared to epilepsy (P = 5.7 × 10− 3) and non-epilepsy disease controls (P = 1.2 × 10− 3). The polygenic burden was driven both by the number of variants per individual, and over-representation of variants likely to be deleterious in the SUDEP cohort. As determined by this study, more than a thousand genes contribute to the observed polygenic burden within the framework of this study. Subsequent gene-based association analysis revealed five possible candidate genes significantly associated with SUDEP or epilepsy, but no one single gene emerges as common to the SUDEP cases. Our findings provide further evidence for a genetic susceptibility to SUDEP, and suggest an extensive polygenic contribution to SUDEP causation. Thus, an overall increased burden of deleterious variants in a highly polygenic background might be important in rendering a given individual more susceptible to SUDEP. Our findings suggest that exome sequencing in people with epilepsy might eventually contribute to generating SUDEP risk estimates, promoting stratified medicine in epilepsy, with the eventual aim of reducing an individual patient's risk of SUDEP. PMID:26501104

  11. Intestinal nutrient absorption - A biomarker for deleterious heavy metals in aquatic environments

    SciTech Connect

    Farmanfarmaian, A. )

    1988-09-01

    The deleterious effects of heavy metals on absorptive processes at the membrane surface will be summarized. Among the deleterious heavy metal chlorides (HgCl{sub 2}, CH{sub 3}HgCl, CdCl{sub 2}, CoCl{sub 2}, SrCl{sub 2}) tested HgCl{sub 2}, CH{sub 3}HgCl, and CdCl{sub 2} inhibit the absorption of several amino acids and sugars (L-leucine, L-methionine, L-isoleucine, L-lysine, cyclolencine, D-glucose, and D-galactose). The dose dependent inhibition of L-leucine uptake by HgCl{sub 2} is shown in a number of fish from different collection sites representing nektonic plankton feeders as well as demersal carnivores. The same type of data is shown for both HgCl{sub 2} and HC{sub 3}HgCl in the case of the commercially important summer flounder. Since the overall rate of intestinal absorption of amino acids and sugars involves the three processes of simple diffusion, protein-mediated facilitated diffusions, and protein-mediated sodium dependent active transport, the inhibition of the overall rate may not be sensitive enough as a biomarker. However, the active component, which alone accumulates essential amino acids in the tissue, appears to be very sensitive and can be used as a biomarker. The terminal tissue-to-medium (T/M) ratio of L-leucine concentration shows a 2-3 fold accumulation in the absence of mercury. Since the diffusional components can at best equilibrate L-leucine across the membrane % inhibition of the active component can be calculated after subtracting 1 from the experimental T/M values. The resulting inhibition is very sever ranging from approximately 50-100% for HgCl{sub 2} and 20-70% for CH{sub 3}HgCl over a range of 5-20 ppm of mercury.

  12. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency.

    PubMed

    Kiezun, Adam; Pulit, Sara L; Francioli, Laurent C; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I; van Duijn, Cornelia M; Slagboom, P Eline; van Ommen, G J B; Wijmenga, Cisca; de Bakker, Paul I W; Sunyaev, Shamil R

    2013-01-01

    Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral variation consists of deleterious alleles segregating at low population frequency due to incessant mutation. To date, studies characterizing selection against deleterious alleles have been based on allele frequency (testing for a relative excess of rare alleles) or ratio of polymorphism to divergence (testing for a relative increase in the number of polymorphic alleles). Here, starting from Maruyama's theoretical prediction (Maruyama T (1974), Am J Hum Genet USA 6:669-673) that a (slightly) deleterious allele is, on average, younger than a neutral allele segregating at the same frequency, we devised an approach to characterize selection based on allelic age. Unlike existing methods, it compares sets of neutral and deleterious sequence variants at the same allele frequency. When applied to human sequence data from the Genome of the Netherlands Project, our approach distinguishes low-frequency coding non-synonymous variants from synonymous and non-coding variants at the same allele frequency and discriminates between sets of variants independently predicted to be benign or damaging for protein structure and function. The results confirm the abundance of slightly deleterious coding variation in humans.

  13. Most of rare missense alleles in humans are deleterious:implications for evolution of complex disease and associationstudies

    SciTech Connect

    Kryukov, Gregory V.; Pennacchio, Len A.; Sunyaev, Shamil R.

    2006-10-24

    The accumulation of mildly deleterious missense mutations inindividual human genomes has been proposed to be a genetic basis forcomplex diseases. The plausibility of this hypothesis depends onquantitative estimates of the prevalence of mildly deleterious de novomutations and polymorphic variants in humans and on the intensity ofselective pressure against them. We combined analysis of mutationscausing human Mendelian diseases, human-chimpanzee divergence andsystematic data on human SNPs and found that about 20 percent of newmissense mutations in humans result in a loss of function, while about 27percent are effectively neutral. Thus, more than half of new missensemutations have mildly deleterious effects. These mutations give rise tomany low frequency deleterious allelic variants in the human populationas evident from a new dataset of 37 genes sequenced in over 1,500individual human chromosomes. Surprisingly, up to 70 percent of lowfrequency missense alleles are mildly deleterious and associated with aheterozygous fitness loss in the range 0.001-0.003. Thus, the low allelefrequency of an amino acid variant can by itself serve as a predictor ofits functional significance. Several recent studies have reported asignificant excess of rare missense variants in disease populationscompared to controls in candidate genes or pathways. These studies wouldbe unlikely to work if most rare variants were neutral or if rarevariants were not a significant contributor to the genetic component ofphenotypic inheritance. Our results provide a justification for thesetypes of candidate gene (pathway) association studies and imply thatmutation-selection balance may be a feasible mechanism for evolution ofsome common diseases.

  14. Reduction of Lysyl Hydroxylase 3 Causes Deleterious Changes in the Deposition and Organization of Extracellular Matrix*

    PubMed Central

    Risteli, Maija; Ruotsalainen, Heli; Salo, Antti M.; Sormunen, Raija; Sipilä, Laura; Baker, Naomi L.; Lamandé, Shireen R.; Vimpari-Kauppinen, Leena; Myllylä, Raili

    2009-01-01

    Lysyl hydroxylase 3 (LH3) is a multifunctional enzyme possessing lysyl hydroxylase, collagen galactosyltransferase, and glucosyltransferase (GGT) activities. We report here an important role for LH3 in the organization of the extracellular matrix (ECM) and cytoskeleton. Deposition of ECM was affected in heterozygous LH3 knock-out mouse embryonic fibroblasts (MEF+/−) and in skin fibroblasts collected from a member of a Finnish epidermolysis bullosa simplex (EBS) family known to be deficient in GGT activity. We show the GGT deficiency to be due to a transcriptional defect in one LH3 allele. The ECM abnormalities also lead to defects in the arrangement of the cytoskeleton in both cell lines. Ultrastructural abnormalities were observed in the skin of heterozygous LH3 knock-out mice indicating that even a moderate decrease in LH3 has deleterious consequences in vivo. The LH3 null allele in the EBS family member and the resulting abnormalities in the organization of the extracellular matrix, similar to those found in MEF+/−, may explain the correlation between the severity of the phenotype and the decrease in GGT activity reported in this family. PMID:19696018

  15. Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data

    PubMed Central

    Watson, Christopher M.; Crinnion, Laura A.; Gurgel‐Gianetti, Juliana; Harrison, Sally M.; Daly, Catherine; Antanavicuite, Agne; Lascelles, Carolina; Markham, Alexander F.; Pena, Sergio D. J.; Bonthron, David T.

    2015-01-01

    ABSTRACT Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease‐causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome‐wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution. PMID:26037133

  16. Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck.

    PubMed

    Balick, Daniel J; Do, Ron; Cassa, Christopher A; Reich, David; Sunyaev, Shamil R

    2015-08-01

    Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in population genetics. On the basis of theoretical analysis and computer simulations, we suggest that this response qualitatively depends on dominance. The number of dominant or additive deleterious alleles per haploid genome is expected to be slightly increased following the bottleneck and re-expansion. In contrast, the number of completely or partially recessive alleles should be sharply reduced. Changes of population size expose differences between recessive and additive selection, potentially providing insight into the prevalence of dominance in natural populations. Specifically, we use a simple statistic, [Formula: see text], where xi represents the derived allele frequency, to compare the number of mutations in different populations, and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. We also provide empirical evidence showing that gene sets associated with autosomal recessive disease in humans may have a BR indicative of recessive selection. Together, these theoretical predictions and empirical observations show that complex demographic history may facilitate rather than impede inference of parameters of natural selection. PMID:26317225

  17. Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual Disability

    PubMed Central

    Hamdan, Fadi F.; Gauthier, Julie; Araki, Yoichi; Lin, Da-Ting; Yoshizawa, Yuhki; Higashi, Kyohei; Park, A-Reum; Spiegelman, Dan; Dobrzeniecka, Sylvia; Piton, Amélie; Tomitori, Hideyuki; Daoud, Hussein; Massicotte, Christine; Henrion, Edouard; Diallo, Ousmane; Shekarabi, Masoud; Marineau, Claude; Shevell, Michael; Maranda, Bruno; Mitchell, Grant; Nadeau, Amélie; D'Anjou, Guy; Vanasse, Michel; Srour, Myriam; Lafrenière, Ronald G.; Drapeau, Pierre; Lacaille, Jean Claude; Kim, Eunjoon; Lee, Jae-Ran; Igarashi, Kazuei; Huganir, Richard L.; Rouleau, Guy A.; Michaud, Jacques L.

    2011-01-01

    Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of their known interacting proteins in 95 sporadic cases of NSID. We found 11 DNMs, including ten potentially deleterious mutations (three nonsense, two splicing, one frameshift, four missense) and one neutral mutation (silent) in eight different genes. Calculation of point-substitution DNM rates per functional and neutral site showed significant excess of functional DNMs compared to neutral ones. De novo truncating and/or splicing mutations in SYNGAP1, STXBP1, and SHANK3 were found in six patients and are likely to be pathogenic. De novo missense mutations were found in KIF1A, GRIN1, CACNG2, and EPB41L1. Functional studies showed that all these missense mutations affect protein function in cell culture systems, suggesting that they may be pathogenic. Sequencing these four genes in 50 additional sporadic cases of NSID identified a second DNM in GRIN1 (c.1679_1681dup/p.Ser560dup). This mutation also affects protein function, consistent with structural predictions. None of these mutations or any other DNMs were identified in these genes in 285 healthy controls. This study highlights the importance of the glutamate receptor complexes in NSID and further supports the role of DNMs in this disorder. PMID:21376300

  18. Deleterious effects of lard-enriched diet on tissues fatty acids composition and hypothalamic insulin actions.

    PubMed

    Dornellas, A P S; Watanabe, R L H; Pimentel, G D; Boldarine, V T; Nascimento, C M O; Oyama, L M; Ghebremeskel, K; Wang, Y; Bueno, A A; Ribeiro, E B

    2015-12-01

    Altered tissue fatty acid (FA) composition may affect mechanisms involved in the control of energy homeostasis, including central insulin actions. In rats fed either standard chow or a lard-enriched chow (high in saturated/low in polyunsaturated FA, HS-LP) for eight weeks, we examined the FA composition of blood, hypothalamus, liver, and retroperitoneal, epididymal and mesenteric adipose tissues. Insulin-induced hypophagia and hypothalamic signaling were evaluated after intracerebroventricular insulin injection. HS-LP feeding increased saturated FA content in adipose tissues and serum while it decreased polyunsaturated FA content of adipose tissues, serum, and liver. Hypothalamic C20:5n-3 and C20:3n-6 contents increased while monounsaturated FA content decreased. HS-LP rats showed hyperglycemia, impaired insulin-induced hypophagia and hypothalamic insulin signaling. The results showed that, upon HS-LP feeding, peripheral tissues underwent potentially deleterious alterations in their FA composition, whist the hypothalamus was relatively preserved. However, hypothalamic insulin signaling and hypophagia were drastically impaired. These findings suggest that impairment of hypothalamic insulin actions by HS-LP feeding was not related to tissue FA composition. PMID:26525379

  19. Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility.

    PubMed

    Davidson, Lien M; Millar, Kate; Jones, Celine; Fatum, Muhammad; Coward, Kevin

    2015-09-01

    Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

  20. Lipoxidation adducts with peptides and proteins: deleterious modifications or signaling mechanisms?

    PubMed

    Domingues, Rosário M; Domingues, Pedro; Melo, Tânia; Pérez-Sala, Dolores; Reis, Ana; Spickett, Corinne M

    2013-10-30

    Protein lipoxidation refers to the modification by electrophilic lipid oxidation products to form covalent adducts, which for many years has been considered as a deleterious consequence of oxidative stress. Oxidized lipids or phospholipids containing carbonyl moieties react readily with lysine to form Schiff bases; alternatively, oxidation products containing α,β-unsaturated moieties are susceptible to nucleophilic attack by cysteine, histidine or lysine residues to yield Michael adducts, overall corresponding to a large number of possible protein adducts. The most common detection methods for lipoxidized proteins take advantage of the presence of reactive carbonyl groups to add labels, or use antibodies. These methods have limitations in terms of specificity and identification of the modification site. The latter question is satisfactorily addressed by mass spectrometry, which enables the characterization of the adduct structure. This has allowed the identification of lipoxidized proteins in physiological and pathological situations. While in many cases lipoxidation interferes with protein function, causing inhibition of enzymatic activity and increased immunogenicity, there are a small number of cases where lipoxidation results in gain of function or activity. For certain proteins lipoxidation may represent a form of redox signaling, although more work is required to confirm the physiological relevance and mechanisms of such processes. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. PMID:23770299

  1. Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck

    PubMed Central

    Balick, Daniel J.; Do, Ron; Cassa, Christopher A.; Reich, David; Sunyaev, Shamil R.

    2015-01-01

    Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in population genetics. On the basis of theoretical analysis and computer simulations, we suggest that this response qualitatively depends on dominance. The number of dominant or additive deleterious alleles per haploid genome is expected to be slightly increased following the bottleneck and re-expansion. In contrast, the number of completely or partially recessive alleles should be sharply reduced. Changes of population size expose differences between recessive and additive selection, potentially providing insight into the prevalence of dominance in natural populations. Specifically, we use a simple statistic, BR≡∑xipop1/∑xjpop2, where x i represents the derived allele frequency, to compare the number of mutations in different populations, and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. We also provide empirical evidence showing that gene sets associated with autosomal recessive disease in humans may have a B R indicative of recessive selection. Together, these theoretical predictions and empirical observations show that complex demographic history may facilitate rather than impede inference of parameters of natural selection. PMID:26317225

  2. Malocclusion and deleterious oral habits among adolescents in a developing area in northeastern Brazil.

    PubMed

    Thomaz, Erika Bárbara Abreu Fonseca; Cangussu, Maria Cristina Teixeira; Assis, Ana Marlúcia Oliveira

    2013-01-01

    Although malocclusions represent a serious public health issue, there is insufficient information about this problem in adolescents in Brazil, especially in poorer areas. The purpose of this cross-sectional study was to estimate the prevalence of facial alterations, dental malocclusions, and deleterious oral habits (DOH) among adolescents in a developing area in northeastern Brazil and to test the hypothesis that the occurrence of DOH in infancy is associated with DOH during adolescence. The study included a probabilistic population-based sample of 2,060 Brazilian students aged 12-15 years. Facial characteristics (type of facial profile, facial symmetry, and passive lip sealing) and malocclusions (Angle and Dental Aesthetic Index, DAI) were evaluated. DOH in infancy and adolescence were evaluated by interviews with the parents and adolescents. Most adolescents presented with normal facial characteristics. The malocclusion prevalence (Angle) was 83%. The DAI ranged from 13 to 69 (mean ± SD: 25.9 ± 7.7). Orthodontic treatment was necessary in 45.1% of the sample. The most prevalent DOH in adolescents were nail biting, object biting, cheek/lip biting, and bruxism, which were associated with finger sucking during infancy (P < 0.05). We conclude that malocclusions and DOH are common among Brazilian adolescents and that finger sucking during infancy may be a good predictor of DOH occurrence during adolescence.

  3. Early mechanical ventilation is deleterious after aspiration-induced lung injury in rabbits.

    PubMed

    Hermon, Michael M; Wassermann, Esther; Pfeiler, Claudia; Pollak, Arnold; Redl, Heinz; Strohmaier, Wolfgang

    2005-01-01

    We investigated whether mechanical ventilation after aspiration is deleterious when started before surfactant therapy. Gas exchange and lung mechanics were measured in rabbits after aspiration either mechanically ventilated before or after lavage with diluted surfactant or Ringer's solution. Lung injury was induced by intratracheal instillation of 2 mL/kg of a betain/HCl pepsin mixture. After 30 min of spontaneous breathing, ventilation was started in 12 rabbits, which were then treated by lavage with diluted surfactant (15 mL/kg body weight; 5.3 mg/mL, group MVpre S) or with Ringer's solution (1 mL/kg; group MVpre R). Another 12 rabbits were treated by lavage while spontaneously breathing and were then connected to the ventilator (MVpost S and MVpost R). Sham control rabbits were mechanically ventilated for 4 h. At the end of experiment, PaO2/FiO2 ratio in MVpost S was five times higher than in MVpre S (P=0.0043). Lung mechanics measurements showed significant difference between MVpre S and MVpost S (P=0.0072). There was histopathologic evidence of decreased lung injury in MVpost S. Immediate initiation of ventilation is harmful when lung injury is induced by aspiration. Further investigations are needed to clarify whether the timing of lavage with diluted surfactant has an impact on the treatment of patients with aspiration or comparable types of direct lung injury. PMID:15614133

  4. Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs

    SciTech Connect

    Yang, Jing; Li, Yuan-Yuan; Li, Yi-Xue; Ye, Zhi-Qiang

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Proper dataset partition can improve the prediction of deleterious nsSNPs. Black-Right-Pointing-Pointer Partition according to original residue type at nsSNP is a good criterion. Black-Right-Pointing-Pointer Similar strategy is supposed promising in other machine learning problems. -- Abstract: Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

  5. Female rats are more susceptible to the deleterious effects of paradoxical sleep deprivation on cognitive performance.

    PubMed

    Hajali, Vahid; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Shabani, Mohammad

    2012-03-17

    Paradoxical sleep deprivation (PSD) may alter subsequent learning and memory capacity. There are differences in both the intensity and direction of responses of the male and female species to the same environmental stimuli and experimental conditions. In the present study, we examined the extent of the effects of PSD for 72h on spatial learning and memory, anxiety-like behavior, corticosterone levels, and the body weight in male as well as in intact and ovariectomized (OVX) female Wistar rats. Multiple platform method was used for PSD induction. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM) task and open field test, respectively. The data showed that PSD could not significantly affect subsequent spatial learning and short-term memory in male rats, while it significantly impaired the performance of the intact and OVX female rats. The PSD-intact and -OVX female rats showed more memory impairment than the PSD-male animals. Those impairments do not appear to be due to elevated stress level, since the plasma corticosterone did not significantly change following PSD induction. The open field data showed that PSD significantly reduced anxiety-like behavior in all experimental groups. In addition, PSD had a reducing effect on the mean body weight of female groups. Such results suggest that the female rats are more vulnerable to the deleterious effects of sleep loss on cognitive performance.

  6. Detection of deleterious genotypes in multigenerational studies. I. Disruptions in individual Arabidopsis actin genes.

    PubMed Central

    Gilliland, L U; McKinney, E C; Asmussen, M A; Meagher, R B

    1998-01-01

    Plant actins are involved in numerous cytoskeletal processes effecting plant development, including cell division plane determination, cell elongation, and cell wall deposition. Arabidopsis thaliana has five ancient subclasses of actin with distinct patterns of spatial and temporal expression. To test their functional roles, we identified insertion mutants in three Arabidopsis actin genes, ACT2, ACT4, and ACT7, representing three subclasses. Adult plants homozygous for the act2-1, act4-1, and act7-1 mutant alleles appear to be robust, morphologically normal, and fully fertile. However, when grown as populations descended from a single heterozygous parent, all three mutant alleles were found at extremely low frequencies relative to the wild-type in the F2 generation. Thus, all three mutant alleles appear to be deleterious. The act2-1 mutant allele was found at normal frequencies in the F1, but at significantly lower frequencies than expected in the F2 and F3 generations. These data suggest that the homozygous act2-1/act2-1 mutant adult plants have a reduced fitness in the 2N sporophytic portion of the life cycle, consistent with the vegetative expression of ACT2. These data are interpreted in light of the extreme conservation of plant actin subclasses and genetic redundancy. PMID:9611186

  7. Deleterious effects of maternal ingestion of cocoa upon fetal ductus arteriosus in late pregnancy.

    PubMed

    Zielinsky, Paulo; Martignoni, Felipe V; Vian, Izabele

    2014-01-01

    Cocoa powder has twice more antioxidants than red wine and three times more than green tea. Ten percent of its weight is made up of flavonoids. Cocoa has antioxidant and anti-inflammatory effects by downregulating cyclooxigenase-2 receptors expression in the endothelium and enhancing nitric oxide bioavailability. There are evidences that while polyphenols ingestion have cardioprotective effects in the adult, it may have deleterious effect on the fetus if ingested by the mother on the third trimester of pregnancy, causing intrauterine fetal ductus arteriosus (DA) constriction. Polyphenols present in many foods and their anti-inflammatory and antinociceptive activities have been shown to be as or more powerful than those of indomethacin. These effects are dependent on the inhibition of modulation of the arachidonic acid and the synthesis of prostaglandins, especially E-2, which is responsible for fetal DA patency. So, we hypothesized that this same mechanism is responsible for the harmful effect of polyphenol-rich foods, such as cocoa, upon the fetal DA after maternal intake of such substances in the third trimester of pregnancy, thereby rising the perspective of a note of caution for pregnant women diet. PMID:25566077

  8. Unraveling the Deleterious Effects of Cancer-Driven STK11 Mutants Through Conformational Sampling Approach

    PubMed Central

    Lopus, Merlin; Paul, D. Meshach; Rajasekaran, R.

    2016-01-01

    Tumor suppressor gene, STK11, encodes for serine–threonine kinase, which has a critical role in regulating cell growth and apoptosis. Mutations of the same lead to the inactivation of STK11, which eventually causes different types of cancer. In this study, we focused on identifying those driver mutations through analyzing structural variations of mutants, viz., D194N, E199K, L160P, and Y49D. Native and the mutants were analyzed to determine their geometrical deviations such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, potential energy, and solvent-accessible surface area using conformational sampling technique. Additionally, the global minimized structure of native and mutants was further analyzed to compute their intramolecular interactions and distribution of secondary structure. Subsequently, simulated thermal denaturation and docking studies were performed to determine their structural variations, which in turn alter the formation of active complex that comprises STK11, STRAD, and MO25. The deleterious effect of the mutants would result in a comparative loss of enzyme function due to variations in their binding energy pertaining to spatial conformation and flexibility. Hence, the structural variations in binding energy exhibited by the mutants, viz., D194N, E199K, L160P, and Y49D, to that of the native, consequently lead to pathogenesis. PMID:27081308

  9. Deleterious effects of maternal ingestion of cocoa upon fetal ductus arteriosus in late pregnancy

    PubMed Central

    Zielinsky, Paulo; Martignoni, Felipe V.; Vian, Izabele

    2014-01-01

    Cocoa powder has twice more antioxidants than red wine and three times more than green tea. Ten percent of its weight is made up of flavonoids. Cocoa has antioxidant and anti-inflammatory effects by downregulating cyclooxigenase-2 receptors expression in the endothelium and enhancing nitric oxide bioavailability. There are evidences that while polyphenols ingestion have cardioprotective effects in the adult, it may have deleterious effect on the fetus if ingested by the mother on the third trimester of pregnancy, causing intrauterine fetal ductus arteriosus (DA) constriction. Polyphenols present in many foods and their anti-inflammatory and antinociceptive activities have been shown to be as or more powerful than those of indomethacin. These effects are dependent on the inhibition of modulation of the arachidonic acid and the synthesis of prostaglandins, especially E-2, which is responsible for fetal DA patency. So, we hypothesized that this same mechanism is responsible for the harmful effect of polyphenol-rich foods, such as cocoa, upon the fetal DA after maternal intake of such substances in the third trimester of pregnancy, thereby rising the perspective of a note of caution for pregnant women diet. PMID:25566077

  10. Accumulation of slightly deleterious mutations in the mitochondrial genome: a hallmark of animal domestication.

    PubMed

    Hughes, Austin L

    2013-02-15

    The hypothesis that domestication leads to a relaxation of purifying selection on mitochondrial (mt) genomes was tested by comparative analysis of mt genes from dog, pig, chicken, and silkworm. The three vertebrate species showed mt genome phylogenies in which domestic and wild isolates were intermingled, whereas the domestic silkworm (Bombyx mori) formed a distinct cluster nested within its closest wild relative (Bombyx mandarina). In spite of these differences in phylogenetic pattern, significantly greater proportions of nonsynonymous SNPs than of synonymous SNPs were unique to the domestic populations of all four species. Likewise, in all four species, significantly greater proportions of RNA-encoding SNPs than of synonymous SNPs were unique to the domestic populations. Thus, domestic populations were characterized by an excess of unique polymorphisms in two categories generally subject to purifying selection: nonsynonymous sites and RNA-encoding sites. Many of these unique polymorphisms thus seem likely to be slightly deleterious; the latter hypothesis was supported by the generally lower gene diversities of polymorphisms unique to domestic populations in comparison to those of polymorphisms shared by domestic and wild populations. PMID:23237775

  11. Morphine has latent deleterious effects on the ventilatory responses to a hypoxic challenge.

    PubMed

    May, Walter J; Gruber, Ryan B; Discala, Joseph F; Puskovic, Veljko; Henderson, Fraser; Palmer, Lisa A; Lewis, Stephen J

    2013-11-01

    The aim of this study was to determine whether morphine depresses the ventilatory responses elicited by a hypoxic challenge (10% O2, 90% N2) in conscious rats at a time when the effects of morphine on arterial blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient and minute ventilation (VM) had completely subsided. In vehicle-treated rats, each episode of hypoxia stimulated ventilatory function and the responses generally subsided during each normoxic period. Morphine (5 mg/kg, i.v.) induced an array of depressant effects on ABG chemistry, A-a gradient and VM (via decreases in tidal volume). Despite resolution of these morphine-induced effects, the first episode of hypoxia elicited substantially smaller increases in VM than in vehicle-treated rats, due mainly to smaller increases in frequency of breathing. The pattern of ventilatory responses during subsequent episodes of hypoxia and normoxia changed substantially in morphine-treated rats. It is evident that morphine has latent deleterious effects on ventilatory responses elicited by hypoxic challenge. PMID:25045593

  12. Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge.

    PubMed

    May, Walter J; Henderson, Fraser; Gruber, Ryan B; Discala, Joseph F; Young, Alex P; Bates, James N; Palmer, Lisa A; Lewis, Stephen J

    2013-08-28

    This study explored the concept that morphine has latent deleterious actions on the ventilatory control systems that respond to a hypoxic-hypercapnic challenge. In this study, we examined the ventilatory responses elicited by hypoxic-hypercapnic challenge in conscious rats at a time when the effects of morphine (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided. Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an increase in pCO2, decreases in pO2 and sO2) and decreases in minute ventilation. Despite the complete resolution of the morphine-induced changes in arterial blood-gas chemistry and minute ventilation and almost complete resolution of the effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to hypoxic-hypercapnic challenge elicited markedly blunted increases in minute ventilation and in peak inspiratory and expiratory flows. These findings demonstrate that (1) the changes in arterial blood-gas chemistry elicited by morphine parallel changes in minute ventilation rather than PIF and PEF, and (2) morphine has latent untoward effects on the ventilatory responses to hypoxic-hypercapnic challenge. These novel findings raise the possibility that patients deemed to have recovered from the acute ventilatory depressant effects of morphine may still be susceptible to the latent effects of this opioid analgesic. The mechanisms underlying these latent effects remain to be elucidated. PMID:25045592

  13. The Accumulation of Deleterious Mutations as a Consequence of Domestication and Improvement in Sunflowers and Other Compositae Crops.

    PubMed

    Renaut, Sebastien; Rieseberg, Loren H

    2015-09-01

    For populations to maintain optimal fitness, harmful mutations must be efficiently purged from the genome. Yet, under circumstances that diminish the effectiveness of natural selection, such as the process of plant and animal domestication, deleterious mutations are predicted to accumulate. Here, we compared the load of deleterious mutations in 21 accessions from natural populations and 19 domesticated accessions of the common sunflower using whole-transcriptome single nucleotide polymorphism data. Although we find that genetic diversity has been greatly reduced during domestication, the remaining mutations were disproportionally biased toward nonsynonymous substitutions. Bioinformatically predicted deleterious mutations affecting protein function were especially strongly over-represented. We also identify similar patterns in two other domesticated species of the sunflower family (globe artichoke and cardoon), indicating that this phenomenon is not due to idiosyncrasies of sunflower domestication or the sunflower genome. Finally, we provide unequivocal evidence that deleterious mutations accumulate in low recombining regions of the genome, due to the reduced efficacy of purifying selection. These results represent a conundrum for crop improvement efforts. Although the elimination of harmful mutations should be a long-term goal of plant and animal breeding programs, it will be difficult to weed them out because of limited recombination.

  14. Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

    PubMed Central

    Kehdy, Fernanda S. G.; Gouveia, Mateus H.; Machado, Moara; Magalhães, Wagner C. S.; Horimoto, Andrea R.; Horta, Bernardo L.; Moreira, Rennan G.; Leal, Thiago P.; Scliar, Marilia O.; Soares-Souza, Giordano B.; Rodrigues-Soares, Fernanda; Araújo, Gilderlanio S.; Zamudio, Roxana; Sant Anna, Hanaisa P.; Santos, Hadassa C.; Duarte, Nubia E.; Fiaccone, Rosemeire L.; Figueiredo, Camila A.; Silva, Thiago M.; Costa, Gustavo N. O.; Beleza, Sandra; Berg, Douglas E.; Cabrera, Lilia; Debortoli, Guilherme; Duarte, Denise; Ghirotto, Silvia; Gilman, Robert H.; Gonçalves, Vanessa F.; Marrero, Andrea R.; Muniz, Yara C.; Weissensteiner, Hansi; Yeager, Meredith; Rodrigues, Laura C.; Barreto, Mauricio L.; Lima-Costa, M. Fernanda; Pereira, Alexandre C.; Rodrigues, Maíra R.; Tarazona-Santos, Eduardo

    2015-01-01

    While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6–8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes. PMID:26124090

  15. Outcome of metastatic breast cancer in selected women with or without deleterious BRCA mutations.

    PubMed

    Bayraktar, S; Gutierrez-Barrera, A M; Lin, H; Elsayegh, N; Tasbas, T; Litton, J K; Ibrahim, N K; Morrow, P K; Green, M; Valero, V; Booser, D J; Hortobagyi, G N; Arun, B K

    2013-06-01

    The aim of this study was to compare the time-to progression and overall survival (OS) in patients with metastatic breast cancer (MBC) with and without deleterious BRCA1/2 mutations. 195 women with MBC who were referred for BRCA genetic testing between 1997 and 2011 were included in the study. Logistic regression models and Cox proportional hazards models were fit to determine the associations between clinical variables and outcomes. Of 195 women with MBC, 21 % (n = 41) were positive for BRCA1/2 mutations. The number of metastatic sites at the time of metastatic disease was not different between BRCA1 versus BRCA2 carriers versus non-carriers (P = 0.77). The site of first metastasis was visceral-only in 70 % of BRCA1 carriers compared to 9 % in BRCA2 carriers and 37 % in non-carriers (P = 0.001). Median follow-up was 2.8 years. BRCA non-carriers and BRCA2 carriers had a longer time-to progression and OS compared to BRCA1 carriers (median time-to progression = 1.3 vs. 0.9 vs. 0.7 years; P = 0.31, and median OS = 4.88 vs. 4.94 vs. 1.34 years; P = 0.0065). In a multivariate model, no association was identified between BRCA positivity and time-to-event outcomes (P > 0.28). In addition, patients with triple-negative MBC carried a poorer prognosis irrespective of their BRCA status (P = 0.058 and P = 0.15 for the interaction term of BRCA status and triple-negative for time-to progression and OS, respectively). Our data indicate that BRCA1 carriers diagnosed with MBC have worse outcomes compared to BRCA2 carriers and non-carriers. However, the differences in outcome did not reach statistical significance likely due to small sample sizes. PMID:23370825

  16. Review: Bucephalus minimus, a deleterious trematode parasite of cockles Cerastoderma spp.

    PubMed

    Magalhães, L; Freitas, R; de Montaudouin, X

    2015-04-01

    Trematodes are the most prevalent and abundant macroparasites in coastal waters. They display a complex life cycle with alternation of free-living and parasitic stages generally involving three host species. The most deleterious stage is in the first intermediate host (a mollusc) where the parasite penetrates as miracidium larvae and asexually multiplicates in sporocysts/rediae to provide cercariae larvae. However, due to basic low prevalence in ecosystems, this system remains difficult to study. Taking the example of the cockle (Cerastoderma edule), an exploited bivalve along North-Eastern Atlantic coasts, and Bucephalus minimus, its most prevalent parasite as first intermediate host, we summarised the 51 most relevant papers (1887-2015). Besides, a 16-year monthly monitoring was performed at Banc d'Arguin (Atlantic coast of France), and allowed to obtain a sufficient number of infected cockles (276 out of 5,420 individuals) in order to provide new information concerning this parasite/host system. Sporocysts (diameter 80-500 μm) and developing cercariae (length 300-500 μm) are not visible before cockle reaches 16-mm shell length and then prevalence increases with host size. Seasonality of infection was not observed but variation of prevalence was significant among years and negatively correlated to the temperature of the former year, which could correspond to the period of infection by miracidium. Seven other species of trematode were identified in cockles as second intermediate host. For six of them, metacercariae abundance per individual was 2 to 12 folds higher in B. minimus-infected cockles, exacerbating the potential negative impact on host. From the parasite point of view, metacercariae can be considered as hitchhikers, taking advantage of the abnormal migration of B. minimus-infected cockles to the sediment surface where they become more vulnerable to predators that are also the final hosts of many of these parasites.

  17. Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

    PubMed

    Kehdy, Fernanda S G; Gouveia, Mateus H; Machado, Moara; Magalhães, Wagner C S; Horimoto, Andrea R; Horta, Bernardo L; Moreira, Rennan G; Leal, Thiago P; Scliar, Marilia O; Soares-Souza, Giordano B; Rodrigues-Soares, Fernanda; Araújo, Gilderlanio S; Zamudio, Roxana; Sant Anna, Hanaisa P; Santos, Hadassa C; Duarte, Nubia E; Fiaccone, Rosemeire L; Figueiredo, Camila A; Silva, Thiago M; Costa, Gustavo N O; Beleza, Sandra; Berg, Douglas E; Cabrera, Lilia; Debortoli, Guilherme; Duarte, Denise; Ghirotto, Silvia; Gilman, Robert H; Gonçalves, Vanessa F; Marrero, Andrea R; Muniz, Yara C; Weissensteiner, Hansi; Yeager, Meredith; Rodrigues, Laura C; Barreto, Mauricio L; Lima-Costa, M Fernanda; Pereira, Alexandre C; Rodrigues, Maíra R; Tarazona-Santos, Eduardo

    2015-07-14

    While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

  18. Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases

    PubMed Central

    Faure, Eric

    2014-01-01

    In nature, organisms are commonly infected by an assemblage of different parasite species or by genetically distinct parasite strains that interact in complex ways. Linked to co-infections, pathocoenosis, a term proposed by M. Grmek in 1969, refers to a pathological state arising from the interactions of diseases within a population and to the temporal and spatial dynamics of all of the diseases. In the long run, malaria was certainly one of the most important component of past pathocoenoses. Today this disease, which affects hundreds of millions of individuals and results in approximately one million deaths each year, is always highly endemic in over 20% of the world and is thus co-endemic with many other diseases. Therefore, the incidences of co-infections and possible direct and indirect interactions with Plasmodium parasites are very high. Both positive and negative interactions between malaria and other diseases caused by parasites belonging to numerous taxa have been described and in some cases, malaria may modify the process of another disease without being affected itself. Interactions include those observed during voluntary malarial infections intended to cure neuro-syphilis or during the enhanced activations of bacterial gastro-intestinal diseases and HIV infections. Complex relationships with multiple effects should also be considered, such as those observed during helminth infections. Moreover, reports dating back over 2000 years suggested that co- and multiple infections have generally deleterious consequences and analyses of historical texts indicated that malaria might exacerbate both plague and cholera, among other diseases. Possible biases affecting the research of etiological agents caused by the protean manifestations of malaria are discussed. A better understanding of the manner by which pathogens, particularly Plasmodium, modulate immune responses is particularly important for the diagnosis, cure, and control of diseases in human populations

  19. Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

    PubMed

    Kehdy, Fernanda S G; Gouveia, Mateus H; Machado, Moara; Magalhães, Wagner C S; Horimoto, Andrea R; Horta, Bernardo L; Moreira, Rennan G; Leal, Thiago P; Scliar, Marilia O; Soares-Souza, Giordano B; Rodrigues-Soares, Fernanda; Araújo, Gilderlanio S; Zamudio, Roxana; Sant Anna, Hanaisa P; Santos, Hadassa C; Duarte, Nubia E; Fiaccone, Rosemeire L; Figueiredo, Camila A; Silva, Thiago M; Costa, Gustavo N O; Beleza, Sandra; Berg, Douglas E; Cabrera, Lilia; Debortoli, Guilherme; Duarte, Denise; Ghirotto, Silvia; Gilman, Robert H; Gonçalves, Vanessa F; Marrero, Andrea R; Muniz, Yara C; Weissensteiner, Hansi; Yeager, Meredith; Rodrigues, Laura C; Barreto, Mauricio L; Lima-Costa, M Fernanda; Pereira, Alexandre C; Rodrigues, Maíra R; Tarazona-Santos, Eduardo

    2015-07-14

    While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes. PMID:26124090

  20. Multiple deleterious effects of experimentally aged sperm in a monogamous bird

    USGS Publications Warehouse

    White, J.; Wagner, R.H.; Helfenstein, F.; Hatch, Shyla A.; Mulard, Hervé; Naves, L.C.; Danchin, E.

    2008-01-01

    Sperm aging is known to be detrimental to reproductive performance. However, this apparently general phenomenon has seldom been studied in an evolutionary context. The negative impact of sperm aging on parental fitness should constitute a strong selective pressure for adaptations to avoid its effects. We studied the impact of sperm aging on black-legged kittiwakes (Rissa tridactyla), a monogamous seabird. Kittiwakes comprise a model system because (i) of evidence that females eject their mates' sperm to prevent fertilization by sperm that would be old and degraded by the time of fertilization and result in reduced reproductive performance and (ii) the lack of extra-pair fertilization in this species makes cryptic female choice an unlikely explanation of postcopulatory sperm ejection by females. We experimentally manipulated the age of the sperm fertilizing kittiwake eggs by fitting males with anti-insemination rings for variable periods of time preceding egg-laying. We found evidence that sperm aging negatively affected four sequential stages of reproduction: fertilization potential, rate of embryonic development, embryonic mortality, and chick condition at hatching. These results may be produced by a continuum of a single process of sperm aging that differentially affects various aspects of development, depending on the degree of damage incurred to the spermatozoa. The marked impact of sperm age on female fitness may thus drive postcopulatory sperm ejection by females. These results provide experimental evidence of deleterious effects of sperm aging on a nondomestic vertebrate, underlining its taxonomic generality and its potential to select for a wide array of adaptations. ?? 2008 by The National Academy of Sciences of the USA.

  1. Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes.

    PubMed

    Eory, Lél; Halligan, Daniel L; Keightley, Peter D

    2010-01-01

    Protein-coding sequences make up only about 1% of the mammalian genome. Much of the remaining 99% has been long assumed to be junk DNA, with little or no functional significance. Here, we show that in hominids, a group with historically low effective population sizes, all classes of noncoding DNA evolve more slowly than ancestral transposable elements and so appear to be subject to significant evolutionary constraints. Under the nearly neutral theory, we expected to see lower levels of selective constraints on most sequence types in hominids than murids, a group that is thought to have a higher effective population size. We found that this is the case for many sequence types examined, the most extreme example being 5'UTRs, for which constraint in hominids is only about one-third that of murids. Surprisingly, however, we observed higher constraints for some sequence types in hominids, notably 4-fold sites, where constraint is more than twice as high as in murids. This implies that more than about one-fifth of mutations at 4-fold sites are effectively selected against in hominids. The higher constraint at 4-fold sites in hominids suggests a more complex protein-coding gene structure than murids and indicates that methods for detecting selection on protein-coding sequences (e.g., using the d(N)/d(S) ratio), with 4-fold sites as a neutral standard, may lead to biased estimates, particularly in hominids. Our constraint estimates imply that 5.4% of nucleotide sites in the human genome are subject to effective negative selection and that there are three times as many constrained sites within noncoding sequences as within protein-coding sequences. Including coding and noncoding sites, we estimate that the genomic deleterious mutation rate U = 4.2. The mutational load predicted under a multiplicative model is therefore about 99% in hominids.

  2. Long-term low carbohydrate diet leads to deleterious metabolic manifestations in diabetic mice.

    PubMed

    Handa, Keiko; Inukai, Kouichi; Onuma, Hirohisa; Kudo, Akihiko; Nakagawa, Fumiyuki; Tsugawa, Kazue; Kitahara, Atsuko; Moriya, Rie; Takahashi, Kazuto; Sumitani, Yoshikazu; Hosaka, Toshio; Kawakami, Hayato; Oyadomari, Seiichi; Ishida, Hitoshi

    2014-01-01

    We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.

  3. Review: Bucephalus minimus, a deleterious trematode parasite of cockles Cerastoderma spp.

    PubMed

    Magalhães, L; Freitas, R; de Montaudouin, X

    2015-04-01

    Trematodes are the most prevalent and abundant macroparasites in coastal waters. They display a complex life cycle with alternation of free-living and parasitic stages generally involving three host species. The most deleterious stage is in the first intermediate host (a mollusc) where the parasite penetrates as miracidium larvae and asexually multiplicates in sporocysts/rediae to provide cercariae larvae. However, due to basic low prevalence in ecosystems, this system remains difficult to study. Taking the example of the cockle (Cerastoderma edule), an exploited bivalve along North-Eastern Atlantic coasts, and Bucephalus minimus, its most prevalent parasite as first intermediate host, we summarised the 51 most relevant papers (1887-2015). Besides, a 16-year monthly monitoring was performed at Banc d'Arguin (Atlantic coast of France), and allowed to obtain a sufficient number of infected cockles (276 out of 5,420 individuals) in order to provide new information concerning this parasite/host system. Sporocysts (diameter 80-500 μm) and developing cercariae (length 300-500 μm) are not visible before cockle reaches 16-mm shell length and then prevalence increases with host size. Seasonality of infection was not observed but variation of prevalence was significant among years and negatively correlated to the temperature of the former year, which could correspond to the period of infection by miracidium. Seven other species of trematode were identified in cockles as second intermediate host. For six of them, metacercariae abundance per individual was 2 to 12 folds higher in B. minimus-infected cockles, exacerbating the potential negative impact on host. From the parasite point of view, metacercariae can be considered as hitchhikers, taking advantage of the abnormal migration of B. minimus-infected cockles to the sediment surface where they become more vulnerable to predators that are also the final hosts of many of these parasites. PMID:25681142

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

    DOE PAGES

    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 1012 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<107. An argument for high Ne values for bacteria has been the high genetic diversity within many bacterial “species,” but thismore » diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimate Ne correctly. Given an estimate ofNe, standard population genetics models imply that 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 ifs 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

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

    SciTech Connect

    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 1012 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<107. An argument for high Ne values for bacteria has been the high genetic diversity within many bacterial “species,” but this diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimate Ne correctly. Given an estimate ofNe, standard population genetics models imply that 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 ifs 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

  6. The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients.

    PubMed

    Soleymanian, Tayebeh; Ghods, Ahad

    2011-11-01

    One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD) is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V ≥ 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3‾ ), Kt/V, normalized protein catabolic rate (nPCR) and body mass index (BMI) in these patients. The mean age of the study patients was 55 ± 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 ± 0.16, pH was 7.40 ± 0.15, serum HCO 3‾ was 23.18 ± 2.38 mEq/L, serum albumin was 4.03 ± 0.56 g/dL, nPCR was 1.00 ± 0.16 g/kg/day, post-dialysis body weight was 58.50 ± 11.50 kg and BMI was 23.47 ± 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004), and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019). On multiple regression analysis, the predictors of serum albumin were serum HCO3‾ and BMI (direct effect) and nPCR (inverse effect). In 17 patients on MHD with serum HCO3‾ <22 mEq/L, there was a significant inverse correlation between HCO 3 and nPCR (r = 0.492, P = 0.045), and these patients had significantly lower serum albumin compared with patients with serum HCO3‾ >22 mEq/L (P = 0.046). These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD.

  7. Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

    PubMed

    Ellingson, Marissa S; Hart, Steven N; Kalari, Krishna R; Suman, Vera; Schahl, Kimberly A; Dockter, Travis J; Felten, Sara J; Sinnwell, Jason P; Thompson, Kevin J; Tang, Xiaojia; Vedell, Peter T; Barman, Poulami; Sicotte, Hugues; Eckel-Passow, Jeanette E; Northfelt, Donald W; Gray, Richard J; McLaughlin, Sarah A; Moreno-Aspitia, Alvaro; Ingle, James N; Moyer, Ann M; Visscher, Daniel W; Jones, Katie; Conners, Amy; McDonough, Michelle; Wieben, Eric D; Wang, Liewei; Weinshilboum, Richard; Boughey, Judy C; Goetz, Matthew P

    2015-09-01

    When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management. PMID:26296701

  8. One step beyond lethal equivalents: characterization of deleterious loci in the rapid cycling Brassica rapa L. base population.

    PubMed

    Lascoux, M; Lee, J K

    1998-10-01

    The total number of lethal equivalents as defined by Morton, Crow and Muller (1956) is a function of three parameters: M, the number of loci at which deleterious mutations can occur, q, the frequency of the deleterious alleles at each locus, and s, their selective value. A new approach based on multi-generation inbreeding data is outlined and used to infer these three parameters as well as the dominance coefficient, h, in a self-incompatible species, Brassica rapa L. Germination and flowering data from thirty bud-selfed lines of fast-cycling B.rapa were assessed over three generations. Germination and flowering were significantly postponed by inbreeding but germination and flowering success were not so strongly decreased. Estimates of the average s values were obtained but it was not possible to get separate estimates of M and q. For both characters, the average dominance coefficient was particularly low. The number of lethal equivalents at the zygotic level was around two for germination and three for flowering, which, owing to the self-incompatibility of B.rapa, is an unexpectedly low value. These results may be explained by past biparental inbreeding which in turn may have increased self-compatibility thus allowing the purging of more deleterious alleles than under strict self-incompatibility.

  9. Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations.

    PubMed

    Rockah-Shmuel, Liat; Tóth-Petróczy, Ágnes; Tawfik, Dan S

    2015-08-01

    Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII's natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins.

  10. Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations

    PubMed Central

    Rockah-Shmuel, Liat; Tóth-Petróczy, Ágnes; Tawfik, Dan S.

    2015-01-01

    Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII’s natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins. PMID:26274323

  11. Materials

    NASA Technical Reports Server (NTRS)

    Glaessgen, Edward H.; Schoeppner, Gregory A.

    2006-01-01

    NASA Langley Research Center has successfully developed an electron beam freeform fabrication (EBF3) process, a rapid metal deposition process that works efficiently with a variety of weldable alloys. The EBF3 process can be used to build a complex, unitized part in a layer-additive fashion, although the more immediate payoff is for use as a manufacturing process for adding details to components fabricated from simplified castings and forgings or plate products. The EBF3 process produces structural metallic parts with strengths comparable to that of wrought product forms and has been demonstrated on aluminum, titanium, and nickel-based alloys to date. The EBF3 process introduces metal wire feedstock into a molten pool that is created and sustained using a focused electron beam in a vacuum environment. Operation in a vacuum ensures a clean process environment and eliminates the need for a consumable shield gas. Advanced metal manufacturing methods such as EBF3 are being explored for fabrication and repair of aerospace structures, offering potential for improvements in cost, weight, and performance to enhance mission success for aircraft, launch vehicles, and spacecraft. Near-term applications of the EBF3 process are most likely to be implemented for cost reduction and lead time reduction through addition of details onto simplified preforms (casting or forging). This is particularly attractive for components with protruding details that would require a significantly large volume of material to be machined away from an oversized forging, offering significant reductions to the buy-to-fly ratio. Future far-term applications promise improved structural efficiency through reduced weight and improved performance by exploiting the layer-additive nature of the EBF3 process to fabricate tailored unitized structures with functionally graded microstructures and compositions.

  12. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients.

    PubMed

    Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; Goold, Carleton; Worringer, Kathleen A; Guan, Wendy; Chan, Karen C; Gai, Hui; Vogt, Daniel; Chen, Ying-Jiun J; Mao, Rong; Chan, Karrie; Rubenstein, John Lr; Madison, Daniel V; Hallmayer, Joachim; Froehlich-Santino, Wendy M; Bernstein, Jonathan A; Dolmetsch, Ricardo E

    2016-01-01

    Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons. PMID:27458797

  13. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients

    PubMed Central

    Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; Goold, Carleton; Worringer, Kathleen A; Guan, Wendy; Chan, Karen C; Gai, Hui; Vogt, Daniel; Chen, Ying-Jiun J; Mao, Rong; Chan, Karrie; Rubenstein, John LR; Madison, Daniel V; Hallmayer, Joachim; Froehlich-Santino, Wendy M; Bernstein, Jonathan A; Dolmetsch, Ricardo E

    2016-01-01

    Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons. DOI: http://dx.doi.org/10.7554/eLife.13073.001 PMID:27458797

  14. A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients

    PubMed Central

    Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; Goold, Carleton; Worringer, Kathleen A; Guan, Wendy; Chan, Karen C; Gai, Hui; Vogt, Daniel; Chen, Ying-Jiun J; Mao, Rong; Chan, Karrie; Rubenstein, John LR; Madison, Daniel V; Hallmayer, Joachim; Froehlich-Santino, Wendy M; Bernstein, Jonathan A; Dolmetsch, Ricardo E

    2016-01-01

    Dravet Syndrome is an intractable form of childhood epilepsy associated with deleterious mutations in SCN1A, the gene encoding neuronal sodium channel Nav1.1. Earlier studies using human induced pluripotent stem cells (iPSCs) have produced mixed results regarding the importance of Nav1.1 in human inhibitory versus excitatory neurons. We studied a Nav1.1 mutation (p.S1328P) identified in a pair of twins with Dravet Syndrome and generated iPSC-derived neurons from these patients. Characterization of the mutant channel revealed a decrease in current amplitude and hypersensitivity to steady-state inactivation. We then differentiated Dravet-Syndrome and control iPSCs into telencephalic excitatory neurons or medial ganglionic eminence (MGE)-like inhibitory neurons. Dravet inhibitory neurons showed deficits in sodium currents and action potential firing, which were rescued by a Nav1.1 transgene, whereas Dravet excitatory neurons were normal. Our study identifies biophysical impairments underlying a deleterious Nav1.1 mutation and supports the hypothesis that Dravet Syndrome arises from defective inhibitory neurons. DOI: http://dx.doi.org/10.7554/eLife.13073.001 PMID:27458797

  15. Evidence for deleterious hepatitis C virus quasispecies mutation loads that differentiate the response patterns in IFN-based antiviral therapy.

    PubMed

    Ren, Yi; Wang, Weihua; Zhang, Xiaoan; Xu, Yanjuan; Di Bisceglie, Adrian M; Fan, Xiaofeng

    2016-02-01

    Viral quasispecies (QS) have long been considered to affect the efficiency of hepatitis C virus (HCV) antiviral therapy, but a correlation between QS diversity and treatment outcomes has not been established conclusively. We previously measured HCV QS diversity by genome-wide quantification of high-resolution mutation load in HCV genotype 1a patients achieving a sustained virological response (1a/SVR) or a null response (1a/null). The current study extended this work into HCV 1a patients experiencing relapse (1a/relapse, n = 19) and genotype 2b patients with SVR (2b/SVR, n = 10). The mean mutation load per patient in 2b/SVR and 1a/relapse was similar, respectively, to 1a/SVR (517.6 ± 174.3 vs 524 ± 278.8 mutations, P = 0.95) and 1a/null (829.2 ± 282.8 vs 805.6 ± 270.7 mutations, P = 0.78). Notably, a deleterious mutation load, as indicated by the percentage of non-synonymous mutations, was highest in 2b/SVR (33.2 ± 8.5%) as compared with 1a/SVR (23.6 ± 7.8%, P = 0.002), 1a/null (18.2 ± 5.1%, P = 1.9 × 10(-7)) or 1a/relapse (17.8 ± 5.3%, P = 1.8) × 10(-6). In the 1a/relapse group, continuous virus evolution was observed with excessive accumulation of a deleterious load (17.8 ± 5.3% vs 35.4 ± 12.9%, P = 3.5 × 10(-6)), supporting the functionality of Muller's ratchet in a treatment-induced population bottleneck. Taken together, the magnitude of HCV mutation load, particularly the deleterious mutation load, provides an evolutionary explanation for the emergence of multiple response patterns as well as an overall high SVR rate in HCV genotype 2 patients. Augmentation of Muller's ratchet represents a potential strategy to reduce or even eliminate viral relapse in HCV antiviral therapy.

  16. A review on the origin and spread of deleterious mutants of the beta-globin gene in Indian populations.

    PubMed

    Das, S K; Talukder, G

    2001-01-01

    Deleterious mutations of the human beta-globin gene are responsible for beta-thalassaemia and other haemoglobinopathies, which are the most common genetic diseases in Indian populations. A highly heterogeneous distribution of those mutations is observed in India and certain mutations are restricted to some extent to particular groups only. The reasons behind the geographical clustering and origin of the mutations in India is a highly debated issue and the evidence is conflicting. Our present article aims at tracing the origin of the deleterious beta-globin mutation and evaluates the role of different evolutionary forces responsible for the spread and present distribution of those mutations in Indian populations, using data from molecular biology and statistical methods. Mutations are generated essentially randomly, but "hot-spot" sites for mutation are reported for the beta-globin gene cluster, indicating sequence dependency of mutation. A single origin of a deleterious beta-globin mutation, followed by recombination (in a hot spot region) and/or interallelic gene conversion (within beta-globin gene) through time is the most plausible hypothesis to explain the association of those mutations with multiple haplotype backgrounds and frameworks. It is suggested that India is the place of origin of HbE and HbD mutations and that they dispersed to other parts of the would by migration. HbS mutants present in Indian populations are not of Middle East origin but rather a fresh mutation is the probable explanation for the prevalence among tribal groups. beta-thalassaemia represents a heterogeneous group of mutant alleles in India. Five common and twelve rare mutations have been reported in variable frequencies among different Indian populations. Gene flow of those mutant alleles from different populations of the world by political, military and commercial interactions possibly accounts for the heterogenous nature of beta-thalassaemia among Indians. A multiple allelic

  17. A new approach to tag design in dolphin telemetry: Computer simulations to minimise deleterious effects

    NASA Astrophysics Data System (ADS)

    Pavlov, V. V.; Wilson, R. P.; Lucke, K.

    2007-02-01

    Remote-sensors and transmitters are powerful devices for studying cetaceans at sea. However, despite substantial progress in microelectronics and miniaturisation of systems, dolphin tags are imperfectly designed; additional drag from tags increases swim costs, compromises swimming capacity and manoeuvrability, and leads to extra loads on the animal's tissue. We propose a new approach to tag design, elaborating basic principles and incorporating design stages to minimise device effects by using computer-aided design. Initially, the operational conditions of the device are defined by quantifying the shape, hydrodynamics and range of the natural deformation of the dolphin body at the tag attachment site (such as close to the dorsal fin). Then, parametric models of both of the dorsal fin and a tag are created using the derived data. The link between parameters of the fin and a tag model allows redesign of tag models according to expected changes of fin geometry (difference in fin shape related with species, sex, and age peculiarities, simulation of the bend of the fin during manoeuvres). A final virtual modelling stage uses iterative improvement of a tag model in a computer fluid dynamics (CFD) environment to enhance tag performance. This new method is considered as a suitable tool of tag design before creation of the physical model of a tag and testing with conventional wind/water tunnel technique. Ultimately, tag materials are selected to conform to the conditions identified by the modelling process and thus help create a physical model of a tag, which should minimise its impact on the animal carrier and thus increase the reliability and quality of the data obtained.

  18. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

    PubMed Central

    Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

    2005-01-01

    Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

  19. WS-SNPs&GO: a web server for predicting the deleterious effect of human protein variants using functional annotation

    PubMed Central

    2013-01-01

    Background SNPs&GO is a method for the prediction of deleterious Single Amino acid Polymorphisms (SAPs) using protein functional annotation. In this work, we present the web server implementation of SNPs&GO (WS-SNPs&GO). The server is based on Support Vector Machines (SVM) and for a given protein, its input comprises: the sequence and/or its three-dimensional structure (when available), a set of target variations and its functional Gene Ontology (GO) terms. The output of the server provides, for each protein variation, the probabilities to be associated to human diseases. Results The server consists of two main components, including updated versions of the sequence-based SNPs&GO (recently scored as one of the best algorithms for predicting deleterious SAPs) and of the structure-based SNPs&GO3d programs. Sequence and structure based algorithms are extensively tested on a large set of annotated variations extracted from the SwissVar database. Selecting a balanced dataset with more than 38,000 SAPs, the sequence-based approach achieves 81% overall accuracy, 0.61 correlation coefficient and an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.88. For the subset of ~6,600 variations mapped on protein structures available at the Protein Data Bank (PDB), the structure-based method scores with 84% overall accuracy, 0.68 correlation coefficient, and 0.91 AUC. When tested on a new blind set of variations, the results of the server are 79% and 83% overall accuracy for the sequence-based and structure-based inputs, respectively. Conclusions WS-SNPs&GO is a valuable tool that includes in a unique framework information derived from protein sequence, structure, evolutionary profile, and protein function. WS-SNPs&GO is freely available at http://snps.biofold.org/snps-and-go. PMID:23819482

  20. Comparison of the deleterious effects of binge drinking-like alcohol exposure in adolescent and adult mice.

    PubMed

    Lacaille, Hélène; Duterte-Boucher, Dominique; Liot, Donovan; Vaudry, Hubert; Naassila, Mickael; Vaudry, David

    2015-03-01

    A major cause of alcohol toxicity is the production of reactive oxygen species generated during ethanol metabolism. The aim of this study was to compare the effect of binge drinking-like alcohol exposure on a panel of genes implicated in oxidative mechanisms in adolescent and adult mice. In adolescent animals, alcohol decreased the expression of genes involved in the repair and protection of oxidative DNA damage such as atr, gpx7, or nudt15 and increased the expression of proapoptotic genes such as casp3. In contrast, in the adult brain, genes activated by alcohol were mainly associated with protective mechanisms that prevent cells from oxidative damage. Whatever the age, iterative binge-like episodes provoked the same deleterious effects as those observed after a single binge episode. In adolescent mice, multiple binge ethanol exposure substantially reduced neurogenesis in the dentate gyrus and impaired short-term memory in the novel object and passive avoidance tests. Taken together, our results indicate that alcohol causes deleterious effects in the adolescent brain which are distinct from those observed in adults. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. The effects of alcohol exposure were investigated on genes involved in oxidative mechanisms. In adolescent animals, alcohol decreased the expression of genes involved in DNA repair, a potential cause of the observed decrease of neurogenesis. In contrast, in the adult brain, alcohol increased the expression of genes associated with antioxidant mechanisms. Apoptosis was increase in all groups and converged with other biochemical alterations to enhance short-term memory impairment in the adolescent brain. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. PMID:25556946

  1. Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

    PubMed Central

    2013-01-01

    Background Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains. PMID:23586671

  2. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction

    PubMed Central

    Odet, Fanny; Pan, Wenqi; Bell, Timothy A.; Goodson, Summer G.; Stevans, Alicia M.; Yun, Zianing; Aylor, David L.; Kao, Chia-Yu; McMillan, Leonard; de Villena, Fernando Pardo-Manuel; O’Brien, Deborah A.

    2015-01-01

    Surveys of inbred strains of mice are standard approaches to determine the heritability and range of phenotypic variation for biomedical traits. In addition, they may lead to the identification of novel phenotypes and models of human disease. Surprisingly, male reproductive phenotypes are among the least-represented traits in the Mouse Phenome Database. Here we report the results of a broad survey of the eight founder inbred strains of both the Collaborative Cross (CC) and the Diversity Outbred populations, two new mouse resources that are being used as platforms for systems genetics and sources of mouse models of human diseases. Our survey includes representatives of the three main subspecies of the house mice and a mix of classical and wild-derived inbred strains. In addition to standard staples of male reproductive phenotyping such as reproductive organ weights, sperm counts, and sperm morphology, our survey includes sperm motility and the first detailed survey of testis histology. As expected for such a broad survey, heritability varies widely among traits. We conclude that although all eight inbred strains are fertile, most display a mix of advantageous and deleterious male reproductive traits. The CAST/EiJ strain is an outlier, with an unusual combination of deleterious male reproductive traits including low sperm counts, high levels of morphologically abnormal sperm, and poor motility. In contrast, sperm from the PWK/PhJ and WSB/EiJ strains had the greatest percentages of normal morphology and vigorous motility. Finally, we report an abnormal testis phenotype that is highly heritable and restricted to the WSB/EiJ strain. This phenotype is characterized by the presence of a large, but variable, number of vacuoles in at least 10% of the seminiferous tubules. The onset of the phenotype between 2 and 3 wk of age is temporally correlated with the formation of the blood-testis barrier. We speculate that this phenotype may play a role in high rates of extinction in

  3. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction.

    PubMed

    Odet, Fanny; Pan, Wenqi; Bell, Timothy A; Goodson, Summer G; Stevans, Alicia M; Yun, Zianing; Aylor, David L; Kao, Chia-Yu; McMillan, Leonard; de Villena, Fernando Pardo-Manuel; O'Brien, Deborah A

    2015-12-01

    Surveys of inbred strains of mice are standard approaches to determine the heritability and range of phenotypic variation for biomedical traits. In addition, they may lead to the identification of novel phenotypes and models of human disease. Surprisingly, male reproductive phenotypes are among the least-represented traits in the Mouse Phenome Database. Here we report the results of a broad survey of the eight founder inbred strains of both the Collaborative Cross (CC) and the Diversity Outbred populations, two new mouse resources that are being used as platforms for systems genetics and sources of mouse models of human diseases. Our survey includes representatives of the three main subspecies of the house mice and a mix of classical and wild-derived inbred strains. In addition to standard staples of male reproductive phenotyping such as reproductive organ weights, sperm counts, and sperm morphology, our survey includes sperm motility and the first detailed survey of testis histology. As expected for such a broad survey, heritability varies widely among traits. We conclude that although all eight inbred strains are fertile, most display a mix of advantageous and deleterious male reproductive traits. The CAST/EiJ strain is an outlier, with an unusual combination of deleterious male reproductive traits including low sperm counts, high levels of morphologically abnormal sperm, and poor motility. In contrast, sperm from the PWK/PhJ and WSB/EiJ strains had the greatest percentages of normal morphology and vigorous motility. Finally, we report an abnormal testis phenotype that is highly heritable and restricted to the WSB/EiJ strain. This phenotype is characterized by the presence of a large, but variable, number of vacuoles in at least 10% of the seminiferous tubules. The onset of the phenotype between 2 and 3 wk of age is temporally correlated with the formation of the blood-testis barrier. We speculate that this phenotype may play a role in high rates of extinction in

  4. Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes

    PubMed Central

    Pengelly, Reuben J.; Arias, Liliana; Martínez, Julio; Upstill-Goddard, Rosanna; Seaby, Eleanor G.; Gibson, Jane; Ennis, Sarah; Collins, Andrew; Briceño, Ignacio

    2016-01-01

    Nonsyndromic Cleft Lip and/or Palate (NSCLP) is regarded as a multifactorial condition in which clefting is an isolated phenotype, distinguished from the largely monogenic, syndromic forms which include clefts among a spectrum of phenotypes. Nonsyndromic clefting has been shown to arise through complex interactions between genetic and environmental factors. However, there is increasing evidence that the broad NSCLP classification may include a proportion of cases showing familial patterns of inheritance and contain highly penetrant deleterious variation in specific genes. Through exome sequencing of multi-case families ascertained in Bogota, Colombia, we identify 28 non-synonymous single nucleotide variants that are considered damaging by at least one predictive score. We discuss the functional impact of candidate variants identified. In one family we find a coding variant in the MSX1 gene which is predicted damaging by multiple scores. This variant is in exon 2, a highly conserved region of the gene. Previous sequencing has suggested that mutations in MSX1 may account for ~2% of NSCLP. Our analysis further supports evidence that a proportion of NSCLP cases arise through monogenic coding mutations, though further work is required to unravel the complex interplay of genetics and environment involved in facial clefting. PMID:27456059

  5. Identification of Deleterious Mutations in Myostatin Gene of Rohu Carp (Labeo rohita) Using Modeling and Molecular Dynamic Simulation Approaches

    PubMed Central

    Rasal, Kiran Dashrath; Chakrapani, Vemulawada; Patra, Swagat Kumar; Mohapatra, Shibani D.; Nayak, Swapnarani; Jena, Sasmita; Sundaray, Jitendra Kumar; Jayasankar, Pallipuram; Barman, Hirak Kumar

    2016-01-01

    The myostatin (MSTN) is a known negative growth regulator of skeletal muscle. The mutated myostatin showed a double-muscular phenotype having a positive significance for the farmed animals. Consequently, adequate information is not available in the teleosts, including farmed rohu carp, Labeo rohita. In the absence of experimental evidence, computational algorithms were utilized in predicting the impact of point mutation of rohu myostatin, especially its structural and functional relationships. The four mutations were generated at different positions (p.D76A, p.Q204P, p.C312Y, and p.D313A) of MSTN protein of rohu. The impacts of each mutant were analyzed using SIFT, I-Mutant 2.0, PANTHER, and PROVEAN, wherein two substitutions (p.D76A and p.Q204P) were predicted as deleterious. The comparative structural analysis of each mutant protein with the native was explored using 3D modeling as well as molecular-dynamic simulation techniques. The simulation showed altered dynamic behaviors concerning RMSD and RMSF, for either p.D76A or p.Q204P substitution, when compared with the native counterpart. Interestingly, incorporated two mutations imposed a significant negative impact on protein structure and stability. The present study provided the first-hand information in identifying possible amino acids, where mutations could be incorporated into MSTN gene of rohu carp including other carps for undertaking further in vivo studies. PMID:27019850

  6. Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes.

    PubMed

    Pengelly, Reuben J; Arias, Liliana; Martínez, Julio; Upstill-Goddard, Rosanna; Seaby, Eleanor G; Gibson, Jane; Ennis, Sarah; Collins, Andrew; Briceño, Ignacio

    2016-01-01

    Nonsyndromic Cleft Lip and/or Palate (NSCLP) is regarded as a multifactorial condition in which clefting is an isolated phenotype, distinguished from the largely monogenic, syndromic forms which include clefts among a spectrum of phenotypes. Nonsyndromic clefting has been shown to arise through complex interactions between genetic and environmental factors. However, there is increasing evidence that the broad NSCLP classification may include a proportion of cases showing familial patterns of inheritance and contain highly penetrant deleterious variation in specific genes. Through exome sequencing of multi-case families ascertained in Bogota, Colombia, we identify 28 non-synonymous single nucleotide variants that are considered damaging by at least one predictive score. We discuss the functional impact of candidate variants identified. In one family we find a coding variant in the MSX1 gene which is predicted damaging by multiple scores. This variant is in exon 2, a highly conserved region of the gene. Previous sequencing has suggested that mutations in MSX1 may account for ~2% of NSCLP. Our analysis further supports evidence that a proportion of NSCLP cases arise through monogenic coding mutations, though further work is required to unravel the complex interplay of genetics and environment involved in facial clefting. PMID:27456059

  7. Quantifying the deleterious role of strong correlations in La1 -xCaxMnO3 at the magnetocaloric transition

    NASA Astrophysics Data System (ADS)

    Turcaud, J. A.; Pereira, A. M.; Cohen, L. F.

    2015-04-01

    Here we study orthorhombic L a1 -xC axMn O3(LCMO ) where x =0.2 ,0.25 , and 0.3 measuring the magnetization, the magneto-Seebeck, and magnetovolume contraction as a function of temperature and magnetic field to examine the influence of lattice, spin, and electronic degrees of freedom. Making the assumption that these contributions are independent of each other allows us to isolate the purely magnetic contribution to the total entropy change. This is compared directly with the value predicted from a mean-field plus Bean-Rodbell model. The model allows the first order character of the transition to be determined, as well as assigning numeric values to the number of magnetic ions that make up preformed magnetic clusters, and to the magnitude of the spread in TC. We quantify how the clusters, the TC spread values, and the electronic contribution, impact deleteriously on the available entropy change in fixed magnetic field, as the first order nature of the transition strengthens.

  8. Activators of the Glutamate-Dependent Acid Resistance System Alleviate Deleterious Effects of YidC Depletion in Escherichia coli▿

    PubMed Central

    Yu, Zhong; Bekker, Martijn; Tramonti, Angela; Cook, Gregory M.; van Ulsen, Peter; Scheffers, Dirk-Jan; de Mattos, Joost Teixeira; De Biase, Daniela; Luirink, Joen

    2011-01-01

    The function of the essential inner membrane protein (IMP) YidC in Escherichia coli has been studied for a limited number of model IMPs and primarily using targeted approaches. These studies suggested that YidC acts at the level of insertion, folding, and quality control of IMPs, both in the context of the Sec translocon and as a separate entity. To further our understanding of YidC's role in IMP biogenesis, we screened a random overexpression library for factors that rescued the growth of cells upon YidC depletion. We found that the overexpression of the GadX and GadY regulators of the glutamate-dependent acid resistance system complemented the growth defect of YidC-depleted cells. Evidence is presented that GadXY overexpression counteracts the deleterious effects of YidC depletion on at least two fronts. First, GadXY prepares the cells for the decrease in respiratory capacity upon the depletion of YidC. Most likely, GadXY-regulated processes reduce the drop in proton-motive force that impairs the fitness of YidC-depleted cells. Second, in GadXY-overproducing cells increased levels of the general chaperone GroEL cofractionate with the inner membranes, which may help to keep newly synthesized inner membrane proteins in an insertion-competent state when YidC levels are limiting. PMID:21216990

  9. The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

    PubMed Central

    Koelle, Katia; Rasmussen, David A

    2015-01-01

    Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates. DOI: http://dx.doi.org/10.7554/eLife.07361.001 PMID:26371556

  10. Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

    PubMed

    van Hooft, Pim; Greyling, Ben J; Getz, Wayne M; van Helden, Paul D; Zwaan, Bas J; Bastos, Armanda D S

    2014-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important

  11. Imipramine protects against the deleterious effects of chronic corticosterone on depression-like behavior, hippocampal reelin expression, and neuronal maturation.

    PubMed

    Fenton, Erin Y; Fournier, Neil M; Lussier, April L; Romay-Tallon, Raquel; Caruncho, Hector J; Kalynchuk, Lisa E

    2015-07-01

    We have hypothesized that a downregulation of reelin and deficient maturation of adult-born hippocampal neurons are important factors in the pathogenesis of depression. This hypothesis is based on previous work showing that depression-like behavior in rats treated with protracted corticosterone develops in concert with decreased dendritic complexity in newborn hippocampal granule neurons and decreased reelin expression in the proliferative subgranular zone of the dentate gyrus. In addition, heterozygous reeler mice with approximately 50% of normal brain levels of reelin are more vulnerable to the depressogenic effects of corticosterone than wild-type mice. The purpose of this experiment was to provide pharmacological validation for the link between reelin, neuronal maturation, and depression by examining whether the deleterious effects of corticosterone on these measures could be prevented by co-administration of the antidepressant imipramine. Rats received corticosterone injections, corticosterone injections plus either 10 or 15mg/kg imipramine injections, or vehicle injections for 21 consecutive days. They were then subjected to the forced swim test to assess depression-like behavior and sacrificed for immunohistochemical examination of immature neuron number and dendritic complexity and the presence of reelin+cells. We found that corticosterone increases depression-like behavior, decreases the number of reelin+cells in the subgranular zone, and decreases the number and complexity of immature neurons in the granule cell layer. All of these behavioral and cellular phenotypes were prevented by imipramine, providing further support for the idea that reelin is involved in the pathogenesis of depression. PMID:25681757

  12. Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function

    PubMed Central

    Chen, Zhe; Qi, Yun; French, Stephanie; Zhang, Guofeng; Garcia, Raúl Covian; Balaban, Robert; Xu, Hong

    2015-01-01

    Various human diseases are associated with mitochondrial DNA (mtDNA) mutations, but heteroplasmy—the coexistence of mutant and wild-type mtDNA—complicates their study. We previously isolated a temperature-lethal mtDNA mutation in Drosophila, mt:CoIT300I, which affects the cytochrome c oxidase subunit I (CoI) locus. In the present study, we found that the decrease in cytochrome c oxidase (COX) activity was ascribable to a temperature-dependent destabilization of cytochrome a heme. Consistently, the viability of homoplasmic flies at 29°C was fully restored by expressing an alternative oxidase, which specifically bypasses the cytochrome chains. Heteroplasmic flies are fully viable and were used to explore the age-related and tissue-specific phenotypes of mt:CoIT300I. The proportion of mt:CoIT300I genome remained constant in somatic tissues along the aging process, suggesting a lack of quality control mechanism to remove defective mitochondria containing a deleterious mtDNA mutation. Using a genetic scheme that expresses a mitochondrially targeted restriction enzyme to induce tissue-specific homoplasmy in heteroplasmic flies, we found that mt:CoIT300I homoplasmy in the eye caused severe neurodegeneration at 29°C. Degeneration was suppressed by improving mitochondrial Ca2+ uptake, suggesting that Ca2+ mishandling contributed to mt:CoIT300I pathogenesis. Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases. PMID:25501370

  13. An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

    PubMed Central

    Ackerman, Christine; Locke, Adam E.; Feingold, Eleanor; Reshey, Benjamin; Espana, Karina; Thusberg, Janita; Mooney, Sean; Bean, Lora J.H.; Dooley, Kenneth J.; Cua, Clifford L.; Reeves, Roger H.; Sherman, Stephanie L.; Maslen, Cheryl L.

    2012-01-01

    About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no CHD (controls = 141) to determine whether rare genetic variants in genes involved in atrioventricular valvuloseptal morphogenesis contribute to AVSD in this sensitized population. We found a significant excess (p < 0.0001) of variants predicted to be deleterious in cases compared to controls. At the most stringent level of filtering, we found potentially damaging variants in nearly 20% of cases but fewer than 3% of controls. The variants with the highest probability of being damaging in cases only were found in six genes: COL6A1, COL6A2, CRELD1, FBLN2, FRZB, and GATA5. Several of the case-specific variants were recurrent in unrelated individuals, occurring in 10% of cases studied. No variants with an equal probability of being damaging were found in controls, demonstrating a highly specific association with AVSD. Of note, all of these genes are in the VEGF-A pathway, even though the candidate genes analyzed in this study represented numerous biochemical and developmental pathways, suggesting that rare variants in the VEGF-A pathway might contribute to the genetic underpinnings of AVSD in humans. PMID:23040494

  14. Quality of the Exotic Parasitoid Cotesia flavipes (Hymenoptera: Braconidae) Does Not Show Deleterious Effects after Inbreeding for 10 Generations

    PubMed Central

    Trevisan, Maíra; De Bortoli, Sergio A.; Vacari, Alessandra M.; Laurentis, Valéria L.; Ramalho, Dagmara G.

    2016-01-01

    Although the parasitoid Cotesia flavipes (Cameron) has proven effective in controlling sugarcane borer Diatraea saccharalis (Fabricius) for many years, concern has arisen over the quality of individuals produced at large scales. The parasitoid has been reared in laboratories in Brazil for more than 40 years, with no new introductions of new populations during that period. Since the quality of the parasitoids was not verified at the time of the species' introduction in Brazil, we do not know if there has been any reduction in quality so far. However, it is possible to determine whether the parasitoid could reduce in quality in future generations. Thus, the objective of this research was to assess the quality of these insects over 10 generations and look for evidence of any loss in quality. We used two populations: one from a biofactory that has been maintained in the laboratory for over 40 years, and an inbred laboratory population. Both were bred, and compared for 10 generations. We wanted to determine what happened to the quality of the parasitoid after 10 generations in an extreme inbreeding situation. To assure inbreeding, newly emerged females were forced to mate with a sibling. Individual females were then allowed to parasitize larvae of D. saccharalis. We performed evaluations for each generation until the tenth generation, and recorded the sex ratio, percentage emergence, number of offspring/females, and longevity of both males and females. Results of the measurements of biological characteristics demonstrated random significant differences between populations; best results were obtained intermittently for both the biofactory population and the inbred population. No significant differences across generations for the same population were observed. Thus, rearing of a C. flavipes population subjected to inbreeding for 10 generations was not sufficient to reveal any deleterious effects of inbreeding. PMID:27509087

  15. Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

    PubMed Central

    Soriano, Sirena; Botella, José A.; Schneuwly, Stephan; Martínez-Sebastián, María J.; Moltó, María D.

    2011-01-01

    Background Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila. Methodology/Principal Findings We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. Conclusion/Significance Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels. PMID:21779322

  16. Quality of the Exotic Parasitoid Cotesia flavipes (Hymenoptera: Braconidae) Does Not Show Deleterious Effects after Inbreeding for 10 Generations.

    PubMed

    Trevisan, Maíra; De Bortoli, Sergio A; Vacari, Alessandra M; Laurentis, Valéria L; Ramalho, Dagmara G

    2016-01-01

    Although the parasitoid Cotesia flavipes (Cameron) has proven effective in controlling sugarcane borer Diatraea saccharalis (Fabricius) for many years, concern has arisen over the quality of individuals produced at large scales. The parasitoid has been reared in laboratories in Brazil for more than 40 years, with no new introductions of new populations during that period. Since the quality of the parasitoids was not verified at the time of the species' introduction in Brazil, we do not know if there has been any reduction in quality so far. However, it is possible to determine whether the parasitoid could reduce in quality in future generations. Thus, the objective of this research was to assess the quality of these insects over 10 generations and look for evidence of any loss in quality. We used two populations: one from a biofactory that has been maintained in the laboratory for over 40 years, and an inbred laboratory population. Both were bred, and compared for 10 generations. We wanted to determine what happened to the quality of the parasitoid after 10 generations in an extreme inbreeding situation. To assure inbreeding, newly emerged females were forced to mate with a sibling. Individual females were then allowed to parasitize larvae of D. saccharalis. We performed evaluations for each generation until the tenth generation, and recorded the sex ratio, percentage emergence, number of offspring/females, and longevity of both males and females. Results of the measurements of biological characteristics demonstrated random significant differences between populations; best results were obtained intermittently for both the biofactory population and the inbred population. No significant differences across generations for the same population were observed. Thus, rearing of a C. flavipes population subjected to inbreeding for 10 generations was not sufficient to reveal any deleterious effects of inbreeding. PMID:27509087

  17. Deleterious effects of water-soluble fraction of petroleum, diesel and gasoline on marine pejerrey Odontesthes argentinensis larvae.

    PubMed

    Rodrigues, Ricardo Vieira; Miranda-Filho, Kleber Campos; Gusmão, Emeline Pereira; Moreira, Cauê Bonucci; Romano, Luis Alberto; Sampaio, Luís André

    2010-04-01

    Accidental discharges and oil spills are frequent around the world. Petroleum-derived hydrocarbons are considered one of the main pollutants of aquatic ecosystem. The importance of petroleum and refined fuels is notorious because today's society depends on them. Researches related to the toxic water-soluble fraction (WSF) of petroleum and derivatives to aquatic biota are scarce. For this reason, deleterious effects of WSF of Brazilian petroleum, automotive diesel and unleaded gasoline to marine pejerrey Odontesthes argentinensis larvae were studied employing toxicity tests and histopathological examination. Each WSF was generated in a laboratory by mixing four parts of seawater with one part of pollutant by approximately 22 h. Larvae were exposed during 96 h to different concentrations of WSF of petroleum, diesel, and gasoline, plus a control. After 96 h of exposure to the different WSFs, three larvae were sampled for histopathological studies. The median lethal concentration after 96 h (LC50) of exposure for WSF of petroleum was equal to 70.68%, it was significantly higher (P<0.05) than the values for WSF of diesel and gasoline, which were 13.46% and 5.48%, respectively. The histological examination of pejerrey larvae exposed to WSF of petroleum, diesel and gasoline after 96 h revealed a variety of lesions in the larvae. The gills, pseudobranchs and esophagus presented epithelial hyperplasia, and the liver presented dilatation of hepatic sinusoids, hepatocitomegaly, bi-nucleated and nuclear degeneration of hepatocytes, such as pyknotic nuclei. The acute toxicity of diesel and gasoline is at least fivefold higher than Brazilian petroleum. However, all toxicants induced histopathological abnormalities in pejerrey larvae. The results are of importance since much attention has been paid to large visible surfaces of petroleum spills instead of potential toxic effects of dissolved aromatic hydrocarbons, which are more available to marine biota.

  18. Chemical Modulation of Mutant mGlu1 Receptors Derived from Deleterious GRM1 Mutations Found in Schizophrenics

    PubMed Central

    2014-01-01

    Schizophrenia is a complex and highly heterogeneous psychiatric disorder whose precise etiology remains elusive. While genome-wide association studies (GWAS) have identified risk genes, they have failed to determine if rare coding single nucleotide polymorphisms (nsSNPs) contribute in schizophrenia. Recently, two independent studies identified 12 rare, deleterious nsSNPS in the GRM1 gene, which encodes the metabotropic glutamate receptor subtype 1 (mGlu1), in schizophrenic patients. Here, we generated stable cell lines expressing the mGlu1 mutant receptors and assessed their pharmacology. Using both the endogenous agonist glutamate and the synthetic agonist DHPG, we found that several of the mutant mGlu1 receptors displayed a loss of function that was not due to a loss in plasma membrane expression. Due to a lack of mGlu1 positive allosteric modulators (PAM) tool compounds active at human mGlu1, we optimized a known mGlu4 PAM/mGlu1 NAM chemotype into a series of potent and selective mGlu1 PAMs by virtue of a double “molecular switch”. Employing mGlu1 PAMs from multiple chemotypes, we demonstrate that the mutant receptors can be potentiated by small molecules and in some cases efficacy restored to that comparable to wild type mGlu1 receptors, suggesting deficits in patients with schizophrenia due to these mutations may be amenable to intervention with an mGlu1 PAM. However, in wild type animals, mGlu1 negative allosteric modulators (NAMs) are efficacious in classic models predictive of antipsychotic activity, whereas we show that mGlu1 PAMs have no effect to slight potentiation in these models. These data further highlight the heterogeneity of schizophrenia and the critical role of patient selection strategies in psychiatric clinical trials to match genotype with therapeutic mechanism. PMID:25137254

  19. Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease.

    PubMed

    Vaziri, Nosratola D; Liu, Shuman; Farzaneh, Seyed H; Nazertehrani, Sohrab; Khazaeli, Mahyar; Zhao, Ying-Yong

    2015-09-01

    Oxidative stress and inflammation play a central role in the progression and complications of chronic kidney disease (CKD) and are, in part, due to impairment of the Nrf2 system, which regulates the expression of antioxidant and detoxifying molecules. Natural Nrf2-inducing phytochemicals have been shown to ameliorate kidney disease in experimental animals. However, owing to adverse outcomes a clinical trial of a synthetic Nrf2 activator, bardoxolone methyl (BARD), in CKD patients was terminated. BARD activates Nrf2 via covalent modification of reactive cysteine residues in the Nrf2 repressor molecule, Keap1. In addition to Nrf2, Keap1 suppresses IKKB, the positive regulator of NF-κB. Treatment with a BARD analog, dh404, at 5-20mg/kg/day in diabetic obese Zucker rats exacerbates, whereas its use at 2mg/kg/day in 5/6 nephrectomized rats attenuates, CKD progression. We, therefore, hypothesized that deleterious effects of high-dose BARD are mediated by the activation of NF-κB. CKD (5/6 nephrectomized) rats were randomized to receive dh404 (2 or 10mg/kg/day) or vehicle for 12 weeks. The vehicle-treated group exhibited glomerulosclerosis; interstitial fibrosis and inflammation; activation of NF-κB; upregulation of oxidative, inflammatory, and fibrotic pathways; and suppression of Nrf2 activity and its key target gene products. Treatment with low-dose dh404 restored Nrf2 activity and expression of its target genes, attenuated activation of NF-κB and fibrotic pathways, and reduced glomerulosclerosis, interstitial fibrosis, and inflammation. In contrast, treatment with a high dh404 dosage intensified proteinuria, renal dysfunction, and histological abnormalities; amplified upregulation of NF-κB and fibrotic pathways; and suppressed the Nrf2 system. Thus therapy with BARD analogs exerts a dose-dependent dimorphic impact on CKD progression.

  20. Skeletal site-specific effects of whole body vibration in mature rats: from deleterious to beneficial frequency-dependent effects.

    PubMed

    Pasqualini, Marion; Lavet, Cédric; Elbadaoui, Mohamed; Vanden-Bossche, Arnaud; Laroche, Norbert; Gnyubkin, Vasily; Vico, Laurence

    2013-07-01

    Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganization and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were seen at 8 Hz. We concluded that

  1. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

    PubMed

    Lopes, Alexandra M; Aston, Kenneth I; Thompson, Emma; Carvalho, Filipa; Gonçalves, João; Huang, Ni; Matthiesen, Rune; Noordam, Michiel J; Quintela, Inés; Ramu, Avinash; Seabra, Catarina; Wilfert, Amy B; Dai, Juncheng; Downie, Jonathan M; Fernandes, Susana; Guo, Xuejiang; Sha, Jiahao; Amorim, António; Barros, Alberto; Carracedo, Angel; Hu, Zhibin; Hurles, Matthew E; Moskovtsev, Sergey; Ober, Carole; Paduch, Darius A; Schiffman, Joshua D; Schlegel, Peter N; Sousa, Mário; Carrell, Douglas T; Conrad, Donald F

    2013-03-01

    Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 × 10(-3)), rare X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 × 10(-3)), and rare Y-linked duplications by 88% (OR 1.88 [1.13-3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5)). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes. PMID:23555275

  2. Deleterious effects in mice of fish-associated methylmercury contained in a diet mimicking the Western populations' average fish consumption.

    PubMed

    Bourdineaud, Jean-Paul; Fujimura, Masatake; Laclau, Muriel; Sawada, Masumi; Yasutake, Akira

    2011-02-01

    Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. Only a few contradictory epidemiological studies are currently available examining the impact of fish consumption on human populations. In the present study, we wanted to address whether a diet mimicking the fish consumption of Western populations could result in observable adverse effects in mice, and whether beneficial nutriments from fish were able to counterbalance the deleterious effects of MeHg, if any. In Europe and the United States, fish consumption varies widely between countries, from 11 to 100 g fish/day. A mid-range value of 25 g fish/day corresponds to a fish contribution to the total diet of 1.25% on a dry weight basis. We decided to supplement a vegetarian-based mouse diet with 1.25% of lyophilized salmon flesh (SAL diet), or 1.25% of a blend of lyophilized cod, tuna, and swordfish (CTS diet). Total mercury contents were 1.15±0.15, 2.3±0.1 and 35.75±0.15 ng Hg/g of food pellets for the control, SAL and CTS diets, respectively. After two months feeding, the CTS diet resulted in significant observable effects as compared to the control and SAL diets, encompassing decreased body growth, altered behavioral performance and increased anxiety level, modification of mitochondrial respiratory protein subunit concentrations in kidney and brain structures, modified gene expression patterns in kidneys, liver and muscles, and a decrease of dopamine concentrations in the hypothalamus and striatum. Our findings have health implications, firstly because 1.25% of CTS flesh in the diet corresponds to an average exposure to MeHg below the WHO provisory tolerable weekly intake (PTWI) (1.6 μg MeHg/kg of body weight/week), and secondly because many people in Western populations, among them women of child-bearing age, are exceeding the PTWI value (for instance, 35% of the French population inhabiting the Atlantic and Mediterranean coasts). PMID

  3. Skeletal site-specific effects of whole body vibration in mature rats: from deleterious to beneficial frequency-dependent effects.

    PubMed

    Pasqualini, Marion; Lavet, Cédric; Elbadaoui, Mohamed; Vanden-Bossche, Arnaud; Laroche, Norbert; Gnyubkin, Vasily; Vico, Laurence

    2013-07-01

    Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganization and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were seen at 8 Hz. We concluded that

  4. Deleterious effects of freezing on osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo.

    PubMed

    James, Aaron W; Levi, Benjamin; Nelson, Emily R; Peng, Michelle; Commons, George W; Lee, Min; Wu, Benjamin; Longaker, Michael T

    2011-03-01

    freezing of ASCs for storage significantly impacts their biology, both in vitro and in vivo. The ability of ASCs to successfully undergo osteogenic differentiation after freeze-thaw is substantively muted, both in vitro and in vivo. The use of recombinant proteins, however, may be used to mitigate the deleterious effects of the freeze-thaw process.

  5. Targeted Deep Sequencing in Multiple-Affected Sibships of European Ancestry Identifies Rare Deleterious Variants in PTPN22 That Confer Risk for Type 1 Diabetes.

    PubMed

    Ge, Yan; Onengut-Gumuscu, Suna; Quinlan, Aaron R; Mackey, Aaron J; Wright, Jocyndra A; Buckner, Jane H; Habib, Tania; Rich, Stephen S; Concannon, Patrick

    2016-03-01

    Despite finding more than 40 risk loci for type 1 diabetes (T1D), the causative variants and genes remain largely unknown. Here, we sought to identify rare deleterious variants of moderate-to-large effects contributing to T1D. We deeply sequenced 301 protein-coding genes located in 49 previously reported T1D risk loci in 70 T1D cases of European ancestry. These cases were selected from putatively high-risk families that had three or more siblings diagnosed with T1D at early ages. A cluster of rare deleterious variants in PTPN22 was identified, including two novel frameshift mutations (ss538819444 and rs371865329) and two missense variants (rs74163663 and rs56048322). Genotyping in 3,609 T1D families showed that rs56048322 was significantly associated with T1D and that this association was independent of the T1D-associated common variant rs2476601. The risk allele at rs56048322 affects splicing of PTPN22, resulting in the production of two alternative PTPN22 transcripts and a novel isoform of LYP (the protein encoded by PTPN22). This isoform competes with the wild-type LYP for binding to CSK and results in hyporesponsiveness of CD4(+) T cells to antigen stimulation in T1D subjects. These findings demonstrate that in addition to common variants, rare deleterious variants in PTPN22 exist and can affect T1D risk.

  6. Evolution- and structure-based computational strategy reveals the impact of deleterious missense mutations on MODY 2 (maturity-onset diabetes of the young, type 2).

    PubMed

    George, Doss C Priya; Chakraborty, Chiranjib; Haneef, S A Syed; Nagasundaram, Nagarajan; Chen, Luonan; Zhu, Hailong

    2014-01-01

    Heterozygous mutations in the central glycolytic enzyme glucokinase (GCK) can result in an autosomal dominant inherited disease, namely maturity-onset diabetes of the young, type 2 (MODY 2). MODY 2 is characterised by early onset: it usually appears before 25 years of age and presents as a mild form of hyperglycaemia. In recent years, the number of known GCK mutations has markedly increased. As a result, interpreting which mutations cause a disease or confer susceptibility to a disease and characterising these deleterious mutations can be a difficult task in large-scale analyses and may be impossible when using a structural perspective. The laborious and time-consuming nature of the experimental analysis led us to attempt to develop a cost-effective computational pipeline for diabetic research that is based on the fundamentals of protein biophysics and that facilitates our understanding of the relationship between phenotypic effects and evolutionary processes. In this study, we investigate missense mutations in the GCK gene by using a wide array of evolution- and structure-based computational methods, such as SIFT, PolyPhen2, PhD-SNP, SNAP, SNPs&GO, fathmm, and Align GVGD. Based on the computational prediction scores obtained using these methods, three mutations, namely E70K, A188T, and W257R, were identified as highly deleterious on the basis of their effects on protein structure and function. Using the evolutionary conservation predictors Consurf and Scorecons, we further demonstrated that most of the predicted deleterious mutations, including E70K, A188T, and W257R, occur in highly conserved regions of GCK. The effects of the mutations on protein stability were computed using PoPMusic 2.1, I-mutant 3.0, and Dmutant. We also conducted molecular dynamics (MD) simulation analysis through in silico modelling to investigate the conformational differences between the native and the mutant proteins and found that the identified deleterious mutations alter the stability

  7. Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset.

    PubMed

    Gordon, Adam S; Tabor, Holly K; Johnson, Andrew D; Snively, Beverly M; Assimes, Themistocles L; Auer, Paul L; Ioannidis, John P A; Peters, Ulrike; Robinson, Jennifer G; Sucheston, Lara E; Wang, Danxin; Sotoodehnia, Nona; Rotter, Jerome I; Psaty, Bruce M; Jackson, Rebecca D; Herrington, David M; O'Donnell, Christopher J; Reiner, Alexander P; Rich, Stephen S; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A

    2014-04-15

    The study of genetic influences on drug response and efficacy ('pharmacogenetics') has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 (CYP) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6-11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP. PMID:24282029

  8. Deleterious Effect of p-Cresol on Human Colonic Epithelial Cells Prevented by Proanthocyanidin-Containing Polyphenol Extracts from Fruits and Proanthocyanidin Bacterial Metabolites.

    PubMed

    Wong, Ximena; Carrasco-Pozo, Catalina; Escobar, Elizabeth; Navarrete, Paola; Blachier, Franςois; Andriamihaja, Mireille; Lan, Annaig; Tomé, Daniel; Cires, Marı́a José; Pastene, Edgar; Gotteland, Martin

    2016-05-11

    The protective effect of proanthocyanidin-containing polyphenol extracts from apples, avocados, cranberries, grapes, or proanthocyanidin microbial metabolites was evaluated in colonic epithelial cells exposed to p-cresol, a deleterious compound produced by the colonic microbiota from l-tyrosine. In HT29 Glc(-/+) cells, p-cresol significantly increased LDH leakage and decreased ATP contents, whereas in Caco-2 cell monolayers, it significantly decreased the transepithelial electrical resistance and increased the paracellular transport of FITC-dextran. The alterations induced by p-cresol in HT29 Glc(-/+) cells were prevented by the extracts from cranberries and avocados, whereas they became worse by extracts from apples and grapes. The proanthocyanidin bacterial metabolites decreased LDH leakage, ameliorating cell viability without improving intracellular ATP. All of the polyphenol extracts and proanthocyanidin bacterial metabolites prevented the p-cresol-induced alterations of barrier function. These results suggest that proanthocyanidin-containing polyphenol extracts and proanthocyanidin metabolites likely contribute to the protection of the colonic mucosa against the deleterious effects of p-cresol. PMID:27039931

  9. Testing the ability of non-methylamine osmolytes present in kidney cells to counteract the deleterious effects of urea on structure, stability and function of proteins.

    PubMed

    Khan, Sheeza; Bano, Zehra; Singh, Laishram R; Hassan, Md Imtaiyaz; Islam, Asimul; Ahmad, Faizan

    2013-01-01

    Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o)) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

  10. Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset

    PubMed Central

    Gordon, Adam S.; Tabor, Holly K.; Johnson, Andrew D.; Snively, Beverly M.; Assimes, Themistocles L.; Auer, Paul L.; Ioannidis, John P.A.; Peters, Ulrike; Robinson, Jennifer G.; Sucheston, Lara E.; Wang, Danxin; Sotoodehnia, Nona; Rotter, Jerome I.; Psaty, Bruce M.; Jackson, Rebecca D.; Herrington, David M.; O'Donnell, Christopher J.; Reiner, Alexander P.; Rich, Stephen S.; Rieder, Mark J.; Bamshad, Michael J.; Nickerson, Deborah A.

    2014-01-01

    The study of genetic influences on drug response and efficacy (‘pharmacogenetics’) has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 (CYP) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6–11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP. PMID:24282029

  11. Testing the Ability of Non-Methylamine Osmolytes Present in Kidney Cells to Counteract the Deleterious Effects of Urea on Structure, Stability and Function of Proteins

    PubMed Central

    Khan, Sheeza; Bano, Zehra; Singh, Laishram R.; Hassan, Md. Imtaiyaz; Islam, Asimul; Ahmad, Faizan

    2013-01-01

    Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔGDo) and functional activity parameters (Km and kcat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively. PMID:24039776

  12. EUROMAT 99, Volume 6, Materials for Buildings and Structures

    NASA Astrophysics Data System (ADS)

    Wittmann, F. H.

    2000-06-01

    Building materials are experiencing degradation phenomena due to the long-term action of the atmospheric components. The understanding of the transport characteristics in concrete is a key issue to mitigate the deleterious consequences. Conventional cement-based materials suffer from a lack of ductility. However, modern cement compositions, fiber materials and additions allow to engineer new products adjusted to the purpose. These and several key topics for modern civil engineering are discussed in this book.

  13. Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Antich, P. P.; Sakhaee, K.; Prior, J.; Gonzales, J.; Gottschalk, F.; Pak, C. Y.

    1992-01-01

    We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

  14. Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model.

    PubMed

    Laemmel, Elisabeth; Segal, Nicolas; Mirshahi, Massoud; Azzazene, Dalel; Le Marchand, Sylvie; Wybier, Marc; Vicaut, Eric; Laredo, Jean-Denis

    2016-06-01

    Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the

  15. Pantoea agglomerans: a mysterious bacterium of evil and good. Part III. Deleterious effects: infections of humans, animals and plants.

    PubMed

    Dutkiewicz, Jacek; Mackiewicz, Barbara; Kinga Lemieszek, Marta; Golec, Marcin; Milanowski, Janusz

    2016-06-01

    Pantoea agglomerans, a bacterium associated with plants, is not an obligate infectious agent in humans. However, it could be a cause of opportunistic human infections, mostly by wound infection with plant material, or as a hospital-acquired infection, mostly in immunocompromised individuals. Wound infection with P. agglomerans usually follow piercing or laceration of skin with a plant thorn, wooden splinter or other plant material and subsequent inoculation of the plant-residing bacteria, mostly during performing of agricultural occupations and gardening, or children playing. Septic arthritis or synovitis appears as a common clinical outcome of exogenous infection with P. agglomerans, others include endophthalmitis, periostitis, endocarditis and osteomyelitis. Another major reason for clinical infection with P. agglomerans is exposure of hospitalized, often immunodeficient individuals to medical equipment or fluids contaminated with this bacterium. Epidemics of nosocomial septicemia with fatal cases have been described in several countries, both in adult and paediatric patients. In most cases, however, the clinical course of the hospital-acquired disease was mild and application of the proper antibiotic treatment led to full recovery. Compared to humans, there are only few reports on infectious diseases caused by Pantoea agglomerans in vertebrate animals. This species has been identified as a possible cause of equine abortion and placentitis and a haemorrhagic disease in dolphin fish (Coryphaena hippurus). P. agglomerans strains occur commonly, usually as symbionts, in insects and other arthropods. Pantoea agglomerans usually occurs in plants as an epi- or endophytic symbiont, often as mutualist. Nevertheless, this species has also also been identified as a cause of diseases in a range of cultivable plants, such as cotton, sweet onion, rice, maize, sorghum, bamboo, walnut, an ornamental plant called Chinese taro (Alocasia cucullata), and a grass called onion couch

  16. Deleterious Rare Variants Reveal Risk for Loss of GABAA Receptor Function in Patients with Genetic Epilepsy and in the General Population

    PubMed Central

    Hernandez, Ciria C.; Klassen, Tara L.; Jackson, Laurel G.; Gurba, Katharine; Hu, Ningning; Macdonald, Robert L.

    2016-01-01

    Genetic epilepsies (GEs) account for approximately 50% of all seizure disorders, and familial forms include mutations in single GABAA receptor subunit genes (GABRs). In 144 sporadic GE cases (GECs), exome sequencing of 237 ion channel genes identified 520 GABR variants. Among these variants, 33 rare variants in 11 GABR genes were present in 24 GECs. To assess functional risk of variants in GECs, we selected 8 variants found in GABRA, 3 in GABRB, and 3 in GABRG and compared them to 18 variants found in the general population for GABRA1 (n = 9), GABRB3 (n = 7), and GABRG2 (n = 2). To identify deleterious variants and gain insight into structure-function relationships, we studied the gating properties, surface expression and structural perturbations of the 32 variants. Significant reduction of GABAA receptor function was strongly associated with variants scored as deleterious and mapped within the N-terminal and transmembrane domains. In addition, 12 out of 17 variants mapped along the β+/α- GABA binding interface, were associated with reduction in channel gating and were predicted to cause structural rearrangements of the receptor by in silico simulations. Missense or nonsense mutations of GABRA1, GABRB3 and GABRG2 primarily impair subunit biogenesis. In contrast, GABR variants affected receptor function by impairing gating, suggesting that different mechanisms are operating in GABR epilepsy susceptibility variants and disease-causing mutations. The functional impact of single GABR variants found in individuals with sporadic GEs warrants the use of molecular diagnosis and will ultimately improve the treatment of genetic epilepsies by using a personalized approach. PMID:27622563

  17. Analysis of Repair Mechanisms following an Induced Double-Strand Break Uncovers Recessive Deleterious Alleles in the Candida albicans Diploid Genome

    PubMed Central

    Feri, Adeline; Loll-Krippleber, Raphaël; Commere, Pierre-Henri; Maufrais, Corinne; Sertour, Natacha; Schwartz, Katja; Sherlock, Gavin; Bougnoux, Marie-Elisabeth

    2016-01-01

    ABSTRACT The diploid genome of the yeast Candida albicans is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH) events. To provide a deeper understanding of the mechanisms leading to LOH, we investigated the repair of a unique DNA double-strand break (DSB) in the laboratory C. albicans SC5314 strain using the I-SceI meganuclease. Upon I-SceI induction, we detected a strong increase in the frequency of LOH events at an I-SceI target locus positioned on chromosome 4 (Chr4), including events spreading from this locus to the proximal telomere. Characterization of the repair events by single nucleotide polymorphism (SNP) typing and whole-genome sequencing revealed a predominance of gene conversions, but we also observed mitotic crossover or break-induced replication events, as well as combinations of independent events. Importantly, progeny that had undergone homozygosis of part or all of Chr4 haplotype B (Chr4B) were inviable. Mining of genome sequencing data for 155 C. albicans isolates allowed the identification of a recessive lethal allele in the GPI16 gene on Chr4B unique to C. albicans strain SC5314 which is responsible for this inviability. Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. Our results demonstrate that recessive lethal alleles in the genomes of C. albicans isolates prevent the occurrence of specific extended LOH events. While these and other recessive lethal and deleterious alleles are likely to accumulate in C. albicans due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the C. albicans species. PMID:27729506

  18. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population.

    PubMed

    Song, Honglin; Cicek, Mine S; Dicks, Ed; Harrington, Patricia; Ramus, Susan J; Cunningham, Julie M; Fridley, Brooke L; Tyrer, Jonathan P; Alsop, Jennifer; Jimenez-Linan, Mercedes; Gayther, Simon A; Goode, Ellen L; Pharoah, Paul D P

    2014-09-01

    The aim of this study was to estimate the contribution of deleterious mutations in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2 to invasive epithelial ovarian cancer (EOC) in the population. The coding sequence and splice site boundaries of all six genes were amplified in germline DNA from 2240 invasive EOC cases and 1535 controls. Barcoded fragment libraries were sequenced using the Illumina GAII or HiSeq and sequence data for each subject de-multiplexed prior to interpretation. GATK and Annovar were used for variant detection and annotation. After quality control 2222 cases (99.2%) and 1528 controls (99.5%) were included in the final analysis. We identified 193 EOC cases (8.7%) carrying a deleterious mutation in at least one gene compared with 10 controls (0.65%). Mutations were most frequent in BRCA1 and BRCA2, with 84 EOC cases (3.8%) carrying a BRCA1 mutation and 94 EOC cases (4.2%) carrying a BRCA2 mutation. The combined BRCA1 and BRCA2 mutation prevalence was 11% in high-grade serous disease. Seventeen EOC cases carried a mutation in a mismatch repair gene, including 10 MSH6 mutation carriers (0.45%) and 4 MSH2 mutation carriers (0.18%). At least 1 in 10 women with high-grade serous EOC has a BRCA1 or BRCA2 mutation. The development of next generation sequencing technologies enables rapid mutation screening for multiple susceptibility genes at once, suggesting that routine clinical testing of all incidence cases should be considered.

  19. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population

    PubMed Central

    Song, Honglin; Cicek, Mine S.; Dicks, Ed; Harrington, Patricia; Ramus, Susan J.; Cunningham, Julie M.; Fridley, Brooke L.; Tyrer, Jonathan P.; Alsop, Jennifer; Jimenez-Linan, Mercedes; Gayther, Simon A.; Goode, Ellen L.; Pharoah, Paul D.P.

    2014-01-01

    The aim of this study was to estimate the contribution of deleterious mutations in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2 to invasive epithelial ovarian cancer (EOC) in the population. The coding sequence and splice site boundaries of all six genes were amplified in germline DNA from 2240 invasive EOC cases and 1535 controls. Barcoded fragment libraries were sequenced using the Illumina GAII or HiSeq and sequence data for each subject de-multiplexed prior to interpretation. GATK and Annovar were used for variant detection and annotation. After quality control 2222 cases (99.2%) and 1528 controls (99.5%) were included in the final analysis. We identified 193 EOC cases (8.7%) carrying a deleterious mutation in at least one gene compared with 10 controls (0.65%). Mutations were most frequent in BRCA1 and BRCA2, with 84 EOC cases (3.8%) carrying a BRCA1 mutation and 94 EOC cases (4.2%) carrying a BRCA2 mutation. The combined BRCA1 and BRCA2 mutation prevalence was 11% in high-grade serous disease. Seventeen EOC cases carried a mutation in a mismatch repair gene, including 10 MSH6 mutation carriers (0.45%) and 4 MSH2 mutation carriers (0.18%). At least 1 in 10 women with high-grade serous EOC has a BRCA1 or BRCA2 mutation. The development of next generation sequencing technologies enables rapid mutation screening for multiple susceptibility genes at once, suggesting that routine clinical testing of all incidence cases should be considered. PMID:24728189

  20. Deleterious Rare Variants Reveal Risk for Loss of GABAA Receptor Function in Patients with Genetic Epilepsy and in the General Population.

    PubMed

    Hernandez, Ciria C; Klassen, Tara L; Jackson, Laurel G; Gurba, Katharine; Hu, Ningning; Noebels, Jeffrey L; Macdonald, Robert L

    2016-01-01

    Genetic epilepsies (GEs) account for approximately 50% of all seizure disorders, and familial forms include mutations in single GABAA receptor subunit genes (GABRs). In 144 sporadic GE cases (GECs), exome sequencing of 237 ion channel genes identified 520 GABR variants. Among these variants, 33 rare variants in 11 GABR genes were present in 24 GECs. To assess functional risk of variants in GECs, we selected 8 variants found in GABRA, 3 in GABRB, and 3 in GABRG and compared them to 18 variants found in the general population for GABRA1 (n = 9), GABRB3 (n = 7), and GABRG2 (n = 2). To identify deleterious variants and gain insight into structure-function relationships, we studied the gating properties, surface expression and structural perturbations of the 32 variants. Significant reduction of GABAA receptor function was strongly associated with variants scored as deleterious and mapped within the N-terminal and transmembrane domains. In addition, 12 out of 17 variants mapped along the β+/α- GABA binding interface, were associated with reduction in channel gating and were predicted to cause structural rearrangements of the receptor by in silico simulations. Missense or nonsense mutations of GABRA1, GABRB3 and GABRG2 primarily impair subunit biogenesis. In contrast, GABR variants affected receptor function by impairing gating, suggesting that different mechanisms are operating in GABR epilepsy susceptibility variants and disease-causing mutations. The functional impact of single GABR variants found in individuals with sporadic GEs warrants the use of molecular diagnosis and will ultimately improve the treatment of genetic epilepsies by using a personalized approach. PMID:27622563

  1. Protective coatings for sensitive materials

    DOEpatents

    Egert, Charles M.

    1997-01-01

    An enhanced protective coating to prevent interaction between constituents of the environment and devices that can be damaged by those constituents. This coating is provided by applying a synergistic combination of diffusion barrier and physical barrier materials. These materials can be, for example, in the form of a plurality of layers of a diffusion barrier and a physical barrier, with these barrier layers being alternated. Further protection in certain instances is provided by including at least one layer of a getter material to actually react with one or more of the deleterious constituents. The coating is illustrated by using alternating layers of an organic coating (such as Parylene-C.TM.) as the diffusion barrier, and a metal coating (such as aluminum) as the physical barrier. For best results there needs to be more than one of at least one of the constituent layers.

  2. Protective coatings for sensitive materials

    DOEpatents

    Egert, C.M.

    1997-08-05

    An enhanced protective coating is disclosed to prevent interaction between constituents of the environment and devices that can be damaged by those constituents. This coating is provided by applying a synergistic combination of diffusion barrier and physical barrier materials. These materials can be, for example, in the form of a plurality of layers of a diffusion barrier and a physical barrier, with these barrier layers being alternated. Further protection in certain instances is provided by including at least one layer of a getter material to actually react with one or more of the deleterious constituents. The coating is illustrated by using alternating layers of an organic coating (such as Parylene-C{trademark}) as the diffusion barrier, and a metal coating (such as aluminum) as the physical barrier. For best results there needs to be more than one of at least one of the constituent layers. 4 figs.

  3. The Balance of Beneficial and Deleterious Health Effects of Quinones: A Case Study of the Chemical Properties of Genistein and Estrone Quinones

    PubMed Central

    Zhang, Qiang; Tu, Tingting; d’Avignon, D. André; Gross, Michael L.

    2009-01-01

    Substances containing a phenolic moiety are often metabolized to quinones whose high reactivity makes them difficult to study. Some of these precursors have clear health benefits, and some quinones themselves are used in cancer therapy, whereas others are deleterious. For example, dietary intake of phytoestrogen, genistein (Gen), seems to play a preventive role in breast cancer (BC) whereas prolonged exposure to chemically similar mammalian estrogens is clearly associated with elevated incidence of BC. Although both can be metabolized to reactive quinones, the catechol estrogen quinones (CEQs) modify DNA by redox cycling and/or depurination via a Michael addition. Here, we report an investigation of the chemical reactivity of Gen and estrone quinones to determine the chemical differences in of these two biologically important molecules. The catechol genistein quinone (CGenQ), has a half life of 4 ± 1 s under physiological condition, as determined by glutathione trapping. It disappears by reacting with H2O to give a dihydrate, CGenQ·(H2O)2, whose structure was proved by NMR. Under reductive conditions, CGenQ·(H2O)2 is readily reduced to reform the catechol genistein (CGen). This reversible oxidation of CGen to CGenQ and the prompt moderation of its reactivity by hydration to CGenQ·(H2O)2 effectively moderates any redox cycling or depurination reaction of CGenQ with DNA. Catechol estrogen quinones, on the other hand, are sufficiently long-lived that they can damage DNA via a Michael addition or by redox cycling. Although the reactivity of CEQ in a nonaqueous solvent is similar to that of CGenQ, its reactivity in aqueous media with the free Ade base is more than 600 times that of CGenQ. These results suggest that rapid hydration of a quinone can moderate its reactivity toward biomolecules, allowing them to express, for example, estrogen-like properties without exhibiting the deleterious properties of redox cycling or directly damaging DNA via depurination

  4. Balance of beneficial and deleterious health effects of quinones: a case study of the chemical properties of genistein and estrone quinones.

    PubMed

    Zhang, Qiang; Tu, Tingting; d'Avignon, D André; Gross, Michael L

    2009-01-28

    Substances containing a phenolic moiety are often metabolized to quinones whose high reactivity makes them difficult to study. Some of these precursors have clear health benefits, and some quinones themselves are used in cancer therapy, whereas others are deleterious. For example, dietary intake of phytoestrogen, genistein (Gen), seems to play a preventive role in breast cancer (BC) whereas prolonged exposure to chemically similar mammalian estrogens is clearly associated with elevated incidence of BC. Although both can be metabolized to reactive quinones, the catechol estrogen quinones (CEQs) modify DNA by redox cycling and/or depurination via a Michael addition. Here, we report an investigation of the chemical reactivity of Gen and estrone quinones to determine the chemical differences of these two biologically important molecules. The catechol genistein quinone (CGenQ), has a half-life of 4 +/- 1 s under physiological condition, as determined by glutathione trapping. It disappears by reacting with H2O to give a dihydrate, CGenQ x (H2O)2, whose structure was proved by NMR. Under reductive conditions, CGenQ x (H2O)2 is readily reduced to reform the catechol genistein (CGen). This reversible oxidation of CGen to CGenQ and the prompt moderation of its reactivity by hydration to CGenQ x (H2O)2 effectively hinders any redox cycling or depurination reaction of CGenQ with DNA. Catechol estrogen quinones, on the other hand, are sufficiently long-lived that they can damage DNA via a Michael addition or by redox cycling. Although the reactivity of CEQ in a nonaqueous solvent is similar to that of CGenQ, its reactivity in aqueous media with the free Ade base is more than 600 times that of CGenQ. These results suggest that rapid hydration of a quinone can moderate its reactivity toward biomolecules, allowing them to express, for example, estrogen-like properties without exhibiting the deleterious properties of redox cycling or directly damaging DNA via depurination reactions.

  5. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain.

    PubMed

    Allam, Ahmed A; Maodaa, Salah N; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns.

  6. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.

    PubMed

    Mecha, M; Feliú, A; Iñigo, P M; Mestre, L; Carrillo-Salinas, F J; Guaza, C

    2013-11-01

    Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.

  7. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  8. Dormancy in Deinococcus sp. UDEC-P1 as a survival strategy to escape from deleterious effects of carbon starvation and temperature.

    PubMed

    Guerra, Matías; González, Karina; González, Carlos; Parra, Boris; Martínez, Miguel

    2015-09-01

    Dormancy is characterized by low metabolism and absence of protein synthesis and cellular division enabling bacterial cells to survive under stress. The aim was to determine if carbon starvation and low temperature are factors that modify the proportion of dormant/active cells in Deinococcus sp. UDEC-P1. By flow cytometry, RedoxSensor Green (RSG) was used to quantify metabolic activity and Propidium Iodide (PI) to evaluate membrane integrity in order to determine the percentage of dormant cells. Cell size and morphology were determined using scanning electronic microscopy. Under carbon starvation at 30°C, Deinococcus sp. UDEC-P1 increased its proportion of dormant cells from 0.1% to 20%, decreased the count of culturable cells and average cell volume decreased 7.1 times. At 4°C, however, the proportion of dormant cells increased only to 6%, without a change in the count of culturable cells and an average cellular volume decrease of 4.1 times and 3% of the dormant cells were able to be awakened. Results indicate a greater proportion of dormant Deinococcus sp. UDEC-P1 cells at 30ºC and it suggests that carbon starvation is more deleterious condition at 30ºC than 4ºC. For this reason Deinococcus sp. UDEC-P1 cells are more likely to enter into dormancy at higher temperature as a strategy to survive.

  9. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain

    PubMed Central

    Allam, Ahmed A.; Maodaa, Salah N.; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. PMID:26966507

  10. Weathering of Roofing Materials-An Overview

    SciTech Connect

    Berdahl, Paul; Akbari, Hashem; Levinson, Ronnen; Miller, William A.

    2006-03-30

    An overview of several aspects of the weathering of roofing materials is presented. Degradation of materials initiated by ultraviolet radiation is discussed for plastics used in roofing, as well as wood and asphalt. Elevated temperatures accelerate many deleterious chemical reactions and hasten diffusion of material components. Effects of moisture include decay of wood, acceleration of corrosion of metals, staining of clay, and freeze-thaw damage. Soiling of roofing materials causes objectionable stains and reduces the solar reflectance of reflective materials. (Soiling of non-reflective materials can also increase solar reflectance.) Soiling can be attributed to biological growth (e.g., cyanobacteria, fungi, algae), deposits of organic and mineral particles, and to the accumulation of flyash, hydrocarbons and soot from combustion.

  11. Ectopic expression of the Brassica SHOOTMERISTEMLESS attenuates the deleterious effects of the auxin transport inhibitor TIBA on somatic embryo number and morphology.

    PubMed

    Elhiti, Mohamed; Stasolla, Claudio

    2011-02-01

    The auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA) is a useful compound for investigating the role of auxin flow during plant growth and development. In Arabidopsis lines, applications of TIBA during the induction phase of somatic embryogenesis inhibit embryo development and induce the differentiation of the meristematic cells of the shoot apical meristem (SAM), leading to the fusion of the cotyledons. These abnormalities were associated to changes in the expression levels of auxin transporter genes (PINs) and endogenous distribution of IAA. Treatments of TIBA caused a rapid accumulation of IAA within the epidermal and cortical root cells of the explants (bent-cotyledon zygotic embryos), as well as in the apical and sub-apical cells of the callus generated by the surface of the cotyledons of the explants. Within the callus only a few cells acquired meristematic characteristics, and this was associated to low expression levels of genes involved in embryogenic cell fate acquisition, such as WUSCHEL (WUS), LEAFY COTYLEDON 1 and 2. All these deleterious effects were attenuated when TIBA was administered to lines over-expressing SHOOT MERISTEMLESS (STM) isolated from Brassica oleracea (Bo), B. napus (Bn), and B. rapa (Br). Of interest, TIBA-treated explants of Arabidopsis lines over-expressing the Brassica STM were able to produce a large number of embryogenic cells and somatic embryos which exhibited a normal morphology and two distinct cotyledons. A proposed reason for this behaviour was ascribed to the ability of the transformed tissue to retain a normal distribution of auxin in the presence of TIBA. Proper localization of auxin might be required for the normal expression of several genes needed for the acquisition of embryogenic competence and formation of somatic embryos.

  12. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  13. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

    PubMed

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  14. Ectopic expression of the Brassica SHOOTMERISTEMLESS attenuates the deleterious effects of the auxin transport inhibitor TIBA on somatic embryo number and morphology.

    PubMed

    Elhiti, Mohamed; Stasolla, Claudio

    2011-02-01

    The auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA) is a useful compound for investigating the role of auxin flow during plant growth and development. In Arabidopsis lines, applications of TIBA during the induction phase of somatic embryogenesis inhibit embryo development and induce the differentiation of the meristematic cells of the shoot apical meristem (SAM), leading to the fusion of the cotyledons. These abnormalities were associated to changes in the expression levels of auxin transporter genes (PINs) and endogenous distribution of IAA. Treatments of TIBA caused a rapid accumulation of IAA within the epidermal and cortical root cells of the explants (bent-cotyledon zygotic embryos), as well as in the apical and sub-apical cells of the callus generated by the surface of the cotyledons of the explants. Within the callus only a few cells acquired meristematic characteristics, and this was associated to low expression levels of genes involved in embryogenic cell fate acquisition, such as WUSCHEL (WUS), LEAFY COTYLEDON 1 and 2. All these deleterious effects were attenuated when TIBA was administered to lines over-expressing SHOOT MERISTEMLESS (STM) isolated from Brassica oleracea (Bo), B. napus (Bn), and B. rapa (Br). Of interest, TIBA-treated explants of Arabidopsis lines over-expressing the Brassica STM were able to produce a large number of embryogenic cells and somatic embryos which exhibited a normal morphology and two distinct cotyledons. A proposed reason for this behaviour was ascribed to the ability of the transformed tissue to retain a normal distribution of auxin in the presence of TIBA. Proper localization of auxin might be required for the normal expression of several genes needed for the acquisition of embryogenic competence and formation of somatic embryos. PMID:21421384

  15. Properties and Modeling of GWAS when Complex Disease Risk Is Due to Non-Complementing, Deleterious Mutations in Genes of Large Effect

    PubMed Central

    Thornton, Kevin R.; Foran, Andrew J.; Long, Anthony D.

    2013-01-01

    Current genome-wide association studies (GWAS) have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE). This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders), and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated. PMID:23437004

  16. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    PubMed Central

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  17. EEG theta/beta ratio as a potential biomarker for attentional control and resilience against deleterious effects of stress on attention.

    PubMed

    Putman, Peter; Verkuil, Bart; Arias-Garcia, Elsa; Pantazi, Ioanna; van Schie, Charlotte

    2014-06-01

    Anxious stress compromises cognitive executive performance. This occurs, for instance, in cognitive performance anxiety (CPA), in which anxiety about one's cognitive performance causes that performance to actually deteriorate (e.g., test anxiety). This is thought to result from a prefrontal cortically (PFC) mediated failure of top-down attentional control over stress-induced automatic processing of threat-related information. In addition, stress-induced increased catecholamine influx into the PFC may directly compromise attentional function. Previous research has suggested that the ratio between resting state electroencephalographic (EEG) low- and high-frequency power (the theta/beta ratio) is related to trait attentional control, which might moderate these effects of stress on attentional function. The goals of the present study were to test the novel prediction that theta/beta ratio moderates the deleterious effects of CPA-like anxious stress on state attentional control and to replicate a previous finding that the theta/beta ratio is related to self-reported trait attentional control. After recording of baseline frontal EEG signals, 77 participants performed a stress induction or a control procedure. Trait attentional control was assessed with the Attentional Control Scale, whereas stress-induced changes in attentional control and anxiety were measured with self-report visual analogue scales. The hypothesized moderating influence of theta/beta ratio on the effects of stress on state attentional control was confirmed. Theta/beta ratio explained 28% of the variance in stress-induced deterioration of self-reported attentional control. The negative relationship between theta/beta ratio and trait attentional control was replicated (r = -.33). The theta/beta ratio reflects, likely prefrontally mediated, attentional control, and should be a useful biomarker for the study of CPA and other anxiety-cognition interactions. PMID:24379166

  18. Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2

    PubMed Central

    Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C.; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

    2013-01-01

    The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10−4) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle. PMID:23762392

  19. Advanced materials for solid oxide fuel cells

    SciTech Connect

    Armstrong, T.R.; Stevenson, J.

    1995-08-01

    The purpose of this research is to improve the properties of the current state-of-the-art materials used for solid oxide fuel cells (SOFCs). The objectives are to: (1) develop materials based on modifications of the state-of-the-art materials; (2) minimize or eliminate stability problems in the cathode, anode, and interconnect; (3) Electrochemically evaluate (in reproducible and controlled laboratory tests) the current state-of-the-art air electrode materials and cathode/electrolyte interfacial properties; (4) Develop accelerated electrochemical test methods to evaluate the performance of SOFCs under controlled and reproducible conditions; and (5) Develop and test materials for use in low-temperature SOFCs. The goal is to modify and improve the current state-of-the-art materials and minimize the total number of cations in each material to avoid negative effects on the materials properties. Materials to reduce potential deleterious interactions, (3) improve thermal, electrical, and electrochemical properties, (4) develop methods to synthesize both state-of-the-art and alternative materials for the simultaneous fabricatoin and consolidation in air of the interconnections and electrodes with the solid electrolyte, and (5) understand electrochemical reactions at materials interfaces and the effects of component composition and processing on those reactions.

  20. Sustainable materials

    NASA Astrophysics Data System (ADS)

    Allwood, Julian M.

    2016-01-01

    Materials influence every aspect of the energy system; therefore, as well as developing new materials for energy generation, materials scientists should engage in public debate about the limitations of future innovations and the conservation of existing materials.

  1. Behavior of Materials Under Conditions of Thermal Stress

    NASA Technical Reports Server (NTRS)

    Manson, S S

    1954-01-01

    A review is presented of available information on the behavior of brittle and ductile materials under conditions of thermal stress and thermal shock. For brittle materials, a simple formula relating physical properties to thermal-shock resistance is derived and used to determine the relative significance of two indices currently in use for rating materials. For ductile materials, thermal-shock resistance depends upon the complex interrelation among several metallurgical variables which seriously affect strength and ductility. These variables are briefly discussed and illustrated from literature sources. The importance of simulating operating conditions in tests for rating materials is especially to be emphasized because of the importance of testing conditions in metallurgy. A number of practical methods that have been used to minimize the deleterious effects of thermal stress and thermal shock are outlined.

  2. Weird materials

    NASA Astrophysics Data System (ADS)

    Astin, Christina; Talbot, Diane; Goodhew, Peter

    2002-11-01

    Heat a material and it gets hotter; heat it enough and it will melt. But some materials will behave rather unexpectedly when heated, and others can act strangely when deformed. Here, three types of weird materials are described - shape memory alloys, Silly Putty® and thermochromic materials - and examples are given of their uses in manufacturing and in the classroom.

  3. Understanding Materials

    ERIC Educational Resources Information Center

    Katsioloudis, Petros J.

    2010-01-01

    Almost everything people have ever done has involved materials. Historical evidence indicates that "engineered materials" have been available and utilized for the benefit of humankind since the Neolithic period, beginning about 10,000 BC. Some of these materials have been in existence for thousands of years. At first, materials consisted of wood,…

  4. Extensive recombination-induced disruption of genetic interactions is highly deleterious but can be partially reversed by small numbers of secondary recombination events.

    PubMed

    Monjane, Adérito L; Martin, Darren P; Lakay, Francisco; Muhire, Brejnev M; Pande, Daniel; Varsani, Arvind; Harkins, Gordon; Shepherd, Dionne N; Rybicki, Edward P

    2014-07-01

    Although homologous recombination can potentially provide viruses with vastly more evolutionary options than are available through mutation alone, there are considerable limits on the adaptive potential of this important evolutionary process. Primary among these is the disruption of favorable coevolved genetic interactions that can occur following the transfer of foreign genetic material into a genome. Although the fitness costs of such disruptions can be severe, in some cases they can be rapidly recouped by either compensatory mutations or secondary recombination events. Here, we used a maize streak virus (MSV) experimental model to explore both the extremes of recombination-induced genetic disruption and the capacity of secondary recombination to adaptively reverse almost lethal recombination events. Starting with two naturally occurring parental viruses, we synthesized two of the most extreme conceivable MSV chimeras, each effectively carrying 182 recombination breakpoints and containing thorough reciprocal mixtures of parental polymorphisms. Although both chimeras were severely defective and apparently noninfectious, neither had individual movement-, encapsidation-, or replication-associated genome regions that were on their own "lethally recombinant." Surprisingly, mixed inoculations of the chimeras yielded symptomatic infections with viruses with secondary recombination events. These recombinants had only 2 to 6 breakpoints, had predominantly inherited the least defective of the chimeric parental genome fragments, and were obviously far more fit than their synthetic parents. It is clearly evident, therefore, that even when recombinationally disrupted virus genomes have extremely low fitness and there are no easily accessible routes to full recovery, small numbers of secondary recombination events can still yield tremendous fitness gains. Importance: Recombination between viruses can generate strains with enhanced pathological properties but also runs the risk

  5. Containerless synthesis of ceramic materials using microwave heating

    NASA Technical Reports Server (NTRS)

    Dunn, B.; Crouch-Baker, S.

    1990-01-01

    It was demonstrated that microwave heating technique may be employed for the synthesis of a number of multicomponent ceramic oxide-based materials, e.g., YBa2Cu3O7 and CuFe2O4. A characteristic, and potentially extremely useful, feature of such synthesis is that they occur in significantly less time than that required using conventional furnace-based techniques. However, the information obtained to date is necessarily rather empirical, and systematic investigations of the use of microwave heating for the synthesis of ceramic materials are required. The synthesis of ceramic materials at high temperatures are often affected by unwanted, deleterious reactions of the reactants and/or products with the reaction container. Consequently, it is of interest to investigate the high temperature synthesis of ceramic materials using microwave heating in a containerless environment.

  6. Material selection

    SciTech Connect

    Tucker, W.G.

    1990-08-01

    The paper summarizes various criteria that can be used in selecting material used in the construction, furnishing, maintenance, and operation of a building. It also summarizes the types of material and product testing that can be especially useful in the selection process. In broad terms, materials in buildings are classified as building materials, furnishings, maintenance materials, and other contents. At any given time, emissions from materials and products in any of these four categories can dominate the impact on indoor air quality (IAQ) in a building. Responsibility for the selection of these materials may be that of the designer, owner, or occupants. Information on IAQ impacts of materials therefore needs to be developed for a wide range of people.

  7. Hazardous materials

    MedlinePlus

    ... people how to work with hazardous materials and waste. There are many different kinds of hazardous materials, including: Chemicals, like some that are used for cleaning Drugs, like chemotherapy to treat cancer Radioactive material that is used for x-rays or ...

  8. Compatibility of refrigerants and lubricants with motor materials. Volume 1, Final report

    SciTech Connect

    Doerr, R.; Kujak, S.

    1993-05-01

    This volume contains the abstract, scope, discussion of results, charts of motor material compatibility, test procedures, material identifications, and 84 pages of data summary tables. Compatibility test results for 11 pure refrigerants and 17 refrigerant-lubricant combinations with 24 motor materials are included. The greatest effect on the motor materials was caused by adsorption followed by desorption of refrigerants at higher temperatures. High internal pressure of the adsorbed refrigerants and their tendency to evolve from the materials resulted in blisters, cracks, internal bubbles in the varnish, and delamination or bubbles in the sheet insulations. The second effect was extraction or dissolution of materials that lead to embrittlement of some sheet insulations. HCFC-22 and HCFC- 22/mineral oil had the most deleterious effects; the materials are expected to be reliable when used with most of the new refrigerants and lubricants. Tables.

  9. Scintillator material

    DOEpatents

    Anderson, David F.; Kross, Brian J.

    1994-01-01

    An improved scintillator material comprising cerium fluoride is disclosed. Cerium fluoride has been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to known scintillator materials such as thallium-doped sodium iodide, barium fluoride and bismuth germanate. As a result, cerium fluoride is favorably suited for use as a scintillator material in positron emission tomography.

  10. Scintillator material

    DOEpatents

    Anderson, David F.; Kross, Brian J.

    1992-01-01

    An improved scintillator material comprising cerium fluoride is disclosed. Cerium fluoride has been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to known scintillator materials such as thallium-doped sodium iodide, barium fluoride and bismuth germanate. As a result, cerium fluoride is favorably suited for use as a scintillator material in positron emission tomography.

  11. Scintillator material

    DOEpatents

    Anderson, D.F.; Kross, B.J.

    1994-06-07

    An improved scintillator material comprising cerium fluoride is disclosed. Cerium fluoride has been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to known scintillator materials such as thallium-doped sodium iodide, barium fluoride and bismuth germanate. As a result, cerium fluoride is favorably suited for use as a scintillator material in positron emission tomography. 4 figs.

  12. Scintillator material

    DOEpatents

    Anderson, D.F.; Kross, B.J.

    1992-07-28

    An improved scintillator material comprising cerium fluoride is disclosed. Cerium fluoride has been found to provide a balance of good stopping power, high light yield and short decay constant that is superior to known scintillator materials such as thallium-doped sodium iodide, barium fluoride and bismuth germanate. As a result, cerium fluoride is favorably suited for use as a scintillator material in positron emission tomography. 4 figs.

  13. Energy Materials.

    ERIC Educational Resources Information Center

    Iowa State Dept. of Public Instruction, Des Moines.

    These resource materials, developed for use by teachers in the elementary and secondary schools, are designed to provide the teacher with a bibliography, questions and answeres, and suggested classroom activities all relating to the energy problem. The materials are designed to develop a conservation ethic and greater understanding of our energy…

  14. Materials Repurposed

    ERIC Educational Resources Information Center

    White, Orvil L.; Townsend, J. Scott

    2008-01-01

    Few teachers find themselves with the support to purchase all of the materials they ideally need to supply their classrooms. Buying one or two simple, ready-made items can put a serious strain on anyone's budget. However, materials for science in the classroom need not be prefabricated or expensive. By looking at the function and purpose of any…

  15. Cermet materials

    DOEpatents

    Kong, Peter C.

    2008-12-23

    A self-cleaning porous cermet material, filter and system utilizing the same may be used in filtering particulate and gaseous pollutants from internal combustion engines having intermetallic and ceramic phases. The porous cermet filter may be made from a transition metal aluminide phase and an alumina phase. Filler materials may be added to increase the porosity or tailor the catalytic properties of the cermet material. Additionally, the cermet material may be reinforced with fibers or screens. The porous filter may also be electrically conductive so that a current may be passed therethrough to heat the filter during use. Further, a heating element may be incorporated into the porous cermet filter during manufacture. This heating element can be coated with a ceramic material to electrically insulate the heating element. An external heating element may also be provided to heat the cermet filter during use.

  16. Composite material

    DOEpatents

    Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O'Neill, Hugh M.

    2012-02-07

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  17. Insulation Material

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Manufactured by Hitco Materials Division of Armco, Inc. a ceramic fiber insulation material known as Refrasil has been used extensively as a heat-absorbing ablative reinforcement for such space systems as rocket motor nozzles, combustion chambers, and re-entry shields. Refrasil fibers are highly porous and do not melt or vaporize until fibers exceed 3,100 degrees Fahrenheit. Due to these and other properties, Refrasil has found utility in a number of industrial high temperature applications where glass, asbestos and other materials fail. Hitco used this insulation to assist Richardson Co., Inc. in the manufacturing of hard rubber and plastic molded battery cases.

  18. Complex Materials

    SciTech Connect

    Cooper, Valentino

    2014-04-17

    Valentino Cooper uses some of the world's most powerful computing to understand how materials work at subatomic levels, studying breakthroughs such as piezoelectrics, which convert mechanical stress to electrical energy.

  19. CURRICULUM MATERIALS.

    ERIC Educational Resources Information Center

    New Jersey State Dept. of Education, Trenton.

    MATERIALS ARE LISTED BY 36 TOPICS ARRANGED IN ALPHABETICAL ORDER. TOPICS INCLUDE APPRENTICE TRAINING, BAKING, DRAFTING, ENGLISH, GLASSBLOWING, HOME ECONOMICS, INDUSTRIAL CHEMISTRY, MACHINE SHOP, NEEDLE TRADES, REFRIGERATION, AND UPHOLSTERY. PRICES ARE GIVEN FOR EACH ITEM. (EL)

  20. Contrast Materials

    MedlinePlus

    ... or other reactions to contrast materials are rare, radiology departments are well-equipped to deal with them. ... is given. However, both the American College of Radiology (ACR) and the European Society of Urogenital Radiology ...

  1. Complex Materials

    ScienceCinema

    Cooper, Valentino

    2016-07-12

    Valentino Cooper uses some of the world's most powerful computing to understand how materials work at subatomic levels, studying breakthroughs such as piezoelectrics, which convert mechanical stress to electrical energy.

  2. Reference Materials

    NASA Astrophysics Data System (ADS)

    Merkus, Henk G.

    Reference materials for measurement of particle size and porosity may be used for calibration or qualification of instruments or for validation of operating procedures or operators. They cover a broad range of materials. On the one hand there are the certified reference materials, for which governmental institutes have certified one or more typical size or porosity values. Then, there is a large group of reference materials from commercial companies. And on the other hand there are typical products in a given line of industry, where size or porosity values come from the analysis laboratory itself or from some round-robin test in a group of industrial laboratories. Their regular application is essential for adequate quality control of particle size and porosity measurement, as required in e.g., ISO 17025 on quality management. In relation to this, some quality requirements for certification are presented.

  3. Perforated Materials

    NASA Technical Reports Server (NTRS)

    1981-01-01

    National Perforating Corporation (NPC) is a supplier of perforated metals, plastics, and other materials. In production of screens, walkways, and other products for all industries, NPC sought to determine the safe loading of such perforated metal products. NERAC supplied NPC an informational package which included the identification of a firm that already accomplished test and evaluation of the strengths of perforated materials. Using the information available from that firm saved NPC money and time.

  4. Propulsion materials

    SciTech Connect

    Wall, Edward J.; Sullivan, Rogelio A.; Gibbs, Jerry L.

    2008-01-01

    The Department of Energy’s (DOE’s) Office of Vehicle Technologies (OVT) is pleased to introduce the FY 2007 Annual Progress Report for the Propulsion Materials Research and Development Program. Together with DOE national laboratories and in partnership with private industry and universities across the United States, the program continues to engage in research and development (R&D) that provides enabling materials technology for fuel-efficient and environmentally friendly commercial and passenger vehicles.

  5. Projections on structures and material strength in the computational context

    NASA Technical Reports Server (NTRS)

    Knauss, Wolfgang G.

    1993-01-01

    The ideas associated with the subsequent viewgraphs are summarized. The primary motivation behind this presentation is to observe that certain macroscopic, microscopic, and submicroscopic phenomena are being understood that have basic influence on understanding the durability and high temperature sensitivity of polymers and polymer-based composites. This understanding covers important issues of long term stability with respect to residual stresses and deformations which can have very deleterious effects on structures used for long periods of time as a result of the heat-involving manufacturing process. Beyond this, important progress is being made in understanding the nonlinear material response of polymers in the fracture context, because the nonlinear mechanics of the material at the tip of a crack, either propagating or ready to do so, is being understood with increasing precision.

  6. Analysis of durability of advanced cementitious materials for rigid pavement construction in California

    SciTech Connect

    Kurtis, K.E.; Monteiro, P.

    1999-04-01

    Caltrans specifications for the construction of rigid pavements require rapid setting, high early strength, superior workability concrete with a desired 30+ year service life. These strict specifications provide the motivations for the investigation of advanced cementitious materials for pavement construction. The cementitious materials under consideration by Caltrans may be classified into four categories: Portland cements and blends, calcium aluminate cements and blends, calcium sulfoaluminate cements, and fly ash-based cements. To achieve the desired 30+ year design life, it is essential to select materials that are expected to exhibit long-term durability. Because most of the cementitious materials under consideration have not been extensively used for pavement construction in the United States, it is essential to characterize the long-term durability of each material. This report provides general information concerning the deleterious reactions that may damage concrete pavements in California. The reactions addressed in this report are sulfate attack, aggregate reactions, corrosion of reinforcing steel, and freeze-thaw action. Specifically, the expected performance of Portland cements and blends, calcium aluminate cements and blends, calcium sulfoaluminate cements, and fly ash-based cements are examined with regard to each of the deleterious reactions listed. Additional consideration is given to any deterioration mechanism that is particular to any of these cement types. Finally, the recommended test program for assessing potential long-term durability with respect to sulfate attack is described.

  7. Parachute materials

    SciTech Connect

    Peterson, C.W.; Johnson, D.W.

    1987-06-01

    The purpose of this paper is to present guidelines for the use of Kevlar and nylon materials in modern parachute systems. Nylon has been used in parachutes for many years, so this discussion will place emphasis upon Kevlar material properties and their application to parachute design and construction. Kevlar-29 is an aramid fiber manufactured by DuPont and is being used on parachute systems requiring high strength-to-weight ratios or sustained strength at high temperatures. Tests of parachutes using Kevlar webbing, braided cords, ribbons, and thread have demonstrated that these Kevlar materials can be used successfully in ribbon parachutes with no detrimental effects on performance. A few changes must be made in the design of a ribbon parachute to accommodate Kevlar's high modulus. Examples of parachutes that use Kevlar suspension lines, radials, ribbons, reefing lines, bridles, and skirt bands are presented to show that they are much lighter and more resistant to aerodynamic heating than all-nylon parachutes. Nylon continues to be an important material for high-performance parachute systems, however. New nylon weaves have resulted in lighter weight, stronger ribbon materials with excellent sewability characteristics.

  8. Materials Overview

    NASA Technical Reports Server (NTRS)

    Draper, Robert

    2001-01-01

    The Materials and Structures for High Performance project has made excellent progress in the development of advanced high-temperature materials and computational materials science tools to enable high-performance, hgh-efficiency, and environmentally compatible propulsion systems. Ceramic matrix composite (CMC) systems with 2700 O F temperature capability are initially being developed for low NO, combustor liners and turbine vanes. The feasibility of pushing CMC technologies to 3000 O F through revolutionary concepts is also being pursued. Achieving fuel savings of 8 to 15 percent requires higher turbine inlet temperatures as well as reductions in engine weight. An advanced disk alloy has been evaluated for application in future engines. Advanced thermal barrier coatings (TBC s) will enable 3200 O F turbine rotor inlet temperature capability. Advanced alloy development and the development of computational tools for the design of these future alloys will further enable attainment of these goals. Innovative lightweight materials, and structural and nozzle aerodynamic concepts are also being developed to reduce the weight of engine static structures to contribute toward overall fuel savings. Rig tests will demonstrate long-term durability of CMC linersand vanes and advanced turbine airfoil alloy systems, as well as fabricability of components with the highest payoff potential using the lightweight materials and structures concepts being developed.

  9. Hardfacing material

    SciTech Connect

    Branagan, Daniel J.

    2012-01-17

    A method of producing a hard metallic material by forming a mixture containing at least 55% iron and at least one of boron, carbon, silicon and phosphorus. The mixture is formed into an alloy and cooled to form a metallic material having a hardness of greater than about 9.2 GPa. The invention includes a method of forming a wire by combining a metal strip and a powder. The metal strip and the powder are rolled to form a wire containing at least 55% iron and from two to seven additional elements including at least one of C, Si and B. The invention also includes a method of forming a hardened surface on a substrate by processing a solid mass to form a powder, applying the powder to a surface to form a layer containing metallic glass, and converting the glass to a crystalline material having a nanocrystalline grain size.

  10. Layered materials

    NASA Astrophysics Data System (ADS)

    Johnson, David; Clarke, Simon; Wiley, John; Koumoto, Kunihito

    2014-06-01

    Layered compounds, materials with a large anisotropy to their bonding, electrical and/or magnetic properties, have been important in the development of solid state chemistry, physics and engineering applications. Layered materials were the initial test bed where chemists developed intercalation chemistry that evolved into the field of topochemical reactions where researchers are able to perform sequential steps to arrive at kinetically stable products that cannot be directly prepared by other approaches. Physicists have used layered compounds to discover and understand novel phenomena made more apparent through reduced dimensionality. The discovery of charge and spin density waves and more recently the remarkable discovery in condensed matter physics of the two-dimensional topological insulating state were discovered in two-dimensional materials. The understanding developed in two-dimensional materials enabled subsequent extension of these and other phenomena into three-dimensional materials. Layered compounds have also been used in many technologies as engineers and scientists used their unique properties to solve challenging technical problems (low temperature ion conduction for batteries, easy shear planes for lubrication in vacuum, edge decorated catalyst sites for catalytic removal of sulfur from oil, etc). The articles that are published in this issue provide an excellent overview of the spectrum of activities that are being pursued, as well as an introduction to some of the most established achievements in the field. Clusters of papers discussing thermoelectric properties, electronic structure and transport properties, growth of single two-dimensional layers, intercalation and more extensive topochemical reactions and the interleaving of two structures to form new materials highlight the breadth of current research in this area. These papers will hopefully serve as a useful guideline for the interested reader to different important aspects in this field and

  11. Squishy Materials

    NASA Astrophysics Data System (ADS)

    Habdas, Piotr; Weeks, Eric R.; Lynn, David G.

    2006-05-01

    Most people do not realize that many substances they use in the kitchen and the bathroom are not simple liquids or solids. Everyone is familiar with three states of matter: solids, liquids, and gases. However, creams, shampoo, toothpaste, and ketchup all have properties of both liquids and solids. This paper describes demonstrations and laboratory exercises1 that show intriguing properties of squishy substances, defined as materials that are not unambiguously solid, liquid, or gas. Unlike some areas of physics, the concepts behind squishy materials are understandable even by beginning students. Squishy physics can be used to show physics questions arising from everyday life and to convey the excitement of current research.

  12. BIOBASED MATERIALS

    EPA Science Inventory

    Biobased materials refer to products that mainly consist of a substance (or substances) derived from living matter (biomass) and either occur naturally or are synthesized, or it may refer to products made by processes that use biomass. Following a strict definition, many common m...

  13. Materials Science

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The Materials Science Program is structured so that NASA s headquarters is responsible for the program content and selection, through the Enterprise Scientist, and MSFC provides for implementation of ground and flight programs with a Discipline Scientist and Discipline Manager. The Discipline Working Group of eminent scientists from outside of NASA acts in an advisory capacity and writes the Discipline Document from which the NRA content is derived. The program is reviewed approximately every three years by groups such as the Committee on Microgravity Research, the National Materials Advisory Board, and the OBPR Maximization and Prioritization (ReMaP) Task Force. The flight program has had as many as twenty-six principal investigators (PIs) in flight or flight definition stage, with the numbers of PIs in the future dependent on the results of the ReMaP Task Force and internal reviews. Each project has a NASA-appointed Project Scientist, considered a half-time job, who assists the PI in understanding and preparing for internal reviews such as the Science Concept Review and Requirements Definition Review. The Project Scientist also insures that the PI gets the maximum science support from MSFC, represents the PI to the MSFC community, and collaborates with the Project Manager to insure the project is well-supported and remains vital. Currently available flight equipment includes the Materials Science Research Rack (MSRR-1) and Microgravity Science Glovebox. Ground based projects fall into one or more of several categories. Intellectual Underpinning of Flight Program projects include theoretical studies backed by modeling and computer simulations; bring to maturity new research, often by young researchers, and may include preliminary short duration low gravity experiments in the KC-135 aircraft or drop tube; enable characterization of data sets from previous flights; and provide thermophysical property determinations to aid PIs. Radiation Shielding and preliminary In

  14. Material Reseach

    NASA Technical Reports Server (NTRS)

    Workman, Gary L.; Rathz, Tom

    1996-01-01

    Containerless processing experiments in space and in ground-based facilities such as the Drop Tube Facility at Marshall Space Flight Center provide a unique capabilty to study materials processing phenomena without the influence of walls on nucleation processes. This research will further develop that capability by new experiments with immesible systems. Nucleation and undercooling phenomena will be monitored using infra-red temperature measurements.

  15. Prosthesis Material

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In this photograph, Sandra Rossi user her NASA-developed prosthesis for the first time. Derived from foam insulation technology used to protect the Space Shuttle External Tank from excessive heat, FAB/CAD, a subsidiary of the Harshberger Prosthetic and Orthotic Center, utilized the technology to replace the heavy, fragile plaster they used to produce master molds for prosthetics. The new material was lighter, cheaper and easier to manufacture than plaster, resulting in lower costs to the customer.

  16. Prosthesis Material

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In this photograph, James Carden uses a NASA-developed prosthesis to moved planks around his home. Derived from foam insulation technology used to protect the Space Shuttle External Tank from excessive heat, FAB/CAD, a subsidiary of the Harshberger Prosthetic and Orthotic Center, utilized the technology to replace the heavy, fragile plaster they used to produce master molds for prosthetics. The new material was lighter, cheaper and easier to manufacture than plaster, resulting in lower costs to the customer.

  17. Prosthesis Material

    NASA Technical Reports Server (NTRS)

    2004-01-01

    In this photograph, Amputee Amie Bradly uses a NASA-developed prosthesis to paint her fingernails. Derived from foam insulation technology used to protect the Space Shuttle External Tank from excessive heat, FAB/CAD, a subsidiary of the Harshberger Prosthetic and Orthotic Center, utilized the technology to replace the heavy, fragile plaster they used to produce master molds for prosthetics. The new material was lighter, cheaper and easier to manufacture than plaster, resulting in lower costs to the customer.

  18. Fullerene materials

    SciTech Connect

    Malhotra, R.; Ruoff, R.S.; Lorents, D.C.

    1995-04-01

    Fullerenes are all-carbon cage molecules. The most celebrated fullerene is the soccer-ball shaped C{sub 60}, which is composed of twenty hexagons and twelve pentagons. Because its structure is reminiscent of the geodesic domes of architect R. Buckminster Fuller, C{sub 60} is called buckminsterfullerene, and all the materials in the family are designated fullerenes. Huffman and Kraetschmer`s discovery unleashed activity around the world as scientists explored production methods, properties, and potential uses of fullerenes. Within a short period, methods for their production in electric arcs, plasmas, and flames were discovered, and several companies began selling fullerenes to the research market. What is remarkable is that in all these methods, carbon atoms assemble themselves into cage structures. The capability for self-assembly points to some inherent stability of these structures that allows their formation. The unusual structure naturally leads to unusual properties. Among them are ready solubility in solvents and a relatively high vapor pressure for a pure carbon material. The young fullerene field has already produced a surprising array of structures for the development of carbon-base materials having completely new and different properties from any that were previously possible.

  19. FOREWORD: Materials metrology Materials metrology

    NASA Astrophysics Data System (ADS)

    Bennett, Seton; Valdés, Joaquin

    2010-04-01

    It seems that so much of modern life is defined by the materials we use. From aircraft to architecture, from cars to communications, from microelectronics to medicine, the development of new materials and the innovative application of existing ones have underpinned the technological advances that have transformed the way we live, work and play. Recognizing the need for a sound technical basis for drafting codes of practice and specifications for advanced materials, the governments of countries of the Economic Summit (G7) and the European Commission signed a Memorandum of Understanding in 1982 to establish the Versailles Project on Advanced Materials and Standards (VAMAS). This project supports international trade by enabling scientific collaboration as a precursor to the drafting of standards. The VAMAS participants recognized the importance of agreeing a reliable, universally accepted basis for the traceability of the measurements on which standards depend for their preparation and implementation. Seeing the need to involve the wider metrology community, VAMAS approached the Comité International des Poids et Mesures (CIPM). Following discussions with NMI Directors and a workshop at the BIPM in February 2005, the CIPM decided to establish an ad hoc Working Group on the metrology applicable to the measurement of material properties. The Working Group presented its conclusions to the CIPM in October 2007 and published its final report in 2008, leading to the signature of a Memorandum of Understanding between VAMAS and the BIPM. This MoU recognizes the work that is already going on in VAMAS as well as in the Consultative Committees of the CIPM and establishes a framework for an ongoing dialogue on issues of materials metrology. The question of what is meant by traceability in the metrology of the properties of materials is particularly vexed when the measurement results depend on a specified procedure. In these cases, confidence in results requires not only traceable

  20. Method of mitigating titanium impurities effects in p-type silicon material for solar cells

    NASA Technical Reports Server (NTRS)

    Salama, A. M. (Inventor)

    1980-01-01

    Microstructural evaluation tests performed on Cu-doped, Ti-doped and Cu/Ti doped p-type silicon single crystal wafers, before and after the solar cell fabrication, and evaluation of both dark forward and reverse I-V characteristic records for the solar cells produced from the corresponding silicon wafers, show that Cu mitigates the unfavorable effects of Ti, and thus provides for higher conversion efficiency, thereby providing an economical way to reduce the deleterious effects of titanium, one of the impurities present in metallurgical grade silicon material.

  1. Alloy materials

    DOEpatents

    Hans Thieme, Cornelis Leo; Thompson, Elliott D.; Fritzemeier, Leslie G.; Cameron, Robert D.; Siegal, Edward J.

    2002-01-01

    An alloy that contains at least two metals and can be used as a substrate for a superconductor is disclosed. The alloy can contain an oxide former. The alloy can have a biaxial or cube texture. The substrate can be used in a multilayer superconductor, which can further include one or more buffer layers disposed between the substrate and the superconductor material. The alloys can be made a by process that involves first rolling the alloy then annealing the alloy. A relatively large volume percentage of the alloy can be formed of grains having a biaxial or cube texture.

  2. Casting materials

    DOEpatents

    Chaudhry, Anil R.; Dzugan, Robert; Harrington, Richard M.; Neece, Faurice D.; Singh, Nipendra P.

    2011-06-14

    A foam material comprises a liquid polymer and a liquid isocyanate which is mixed to make a solution that is poured, injected or otherwise deposited into a corresponding mold. A reaction from the mixture of the liquid polymer and liquid isocyanate inside the mold forms a thermally collapsible foam structure having a shape that corresponds to the inside surface configuration of the mold and a skin that is continuous and unbroken. Once the reaction is complete, the foam pattern is removed from the mold and may be used as a pattern in any number of conventional casting processes.

  3. Construction material

    DOEpatents

    Wagh, Arun S.; Antink, Allison L.

    2008-07-22

    A structural material of a polystyrene base and the reaction product of the polystyrene base and a solid phosphate ceramic is applied as a slurry which includes one or more of a metal oxide or a metal hydroxide with a source of phosphate to produce a phosphate ceramic and a poly (acrylic acid or acrylate) or combinations or salts thereof and polystyrene or MgO applied to the polystyrene base and allowed to cure so that the dried aqueous slurry chemically bonds to the polystyrene base. A method is also disclosed of applying the slurry to the polystyrene base.

  4. Corrosion of high temperature metallic materials in VHTR

    NASA Astrophysics Data System (ADS)

    Cabet, C.; Rouillard, F.

    2009-07-01

    Helium coolant of High Temperature Reactors is expected to contain impurities which can interact with structural nickel base metallic materials at elevated temperatures. A continuous, self-healing, chromia-based surface scale is needed to act as a barrier against the reactive gasses. However in specific operational conditions, a process occurs at high temperature which irreversibly reduces the chromia layer. The unprotected alloy can then suffer from deleterious corrosion phenomena, such as carburization or decarburization, which can significantly impact the mechanical stability. First, control of the helium chemistry can be used to mitigate the high temperature corrosion of nickel base alloys by suppressing the chromia reduction reaction. Optimization of the alloy composition is a further solution as chromia forming alloys exhibit different oxidation rates in relation to their content of minor reactive elements. Data published on Alloy 617 and Alloy 230 is reviewed in the present paper.

  5. Study of the influence of hole quality on composite materials

    NASA Technical Reports Server (NTRS)

    Pengra, J. J.

    1980-01-01

    The influence of hole quality on the structural behavior of composite materials was investigated. From an industry survey it was determined that the most frequent imperfections encountered during hole fabrication are chipout, delamination, and oversize conditions. These hole flaw types were generated in critical areas of static, compression, and fatigue specimens fabricated from T300/5208 graphite/epoxy system. The specimens were tested in static and cyclic pin bearing modes in addition to compression loading. Results of these tests are presented and discussed. The hole chipout defect reduced the static and cyclic endurance characteristics. Oversize holes also lowered the cyclic pin bearing endurance, but had no influence of the static pin bearing characteristics. Delamination had no insignificant influence on the static tension and cyclic pin bearing characteristics. Compression tests demonstrated a deleterious effect for chipout of delamination defects. Hole quality requirements proposed are discussed.

  6. MATERIAL PROCESSING FOR SELF-ASSEMBLING MACHINE SYSTEMS

    SciTech Connect

    K. LACKNER; D. BUTT; C. WENDT

    1999-06-01

    We are developing an important aspect of a new technology based on self-reproducing machine systems. Such systems could overcome resource limitations and control the deleterious side effects of human activities on the environment. Machine systems capable of building themselves promise an increase in industrial productivity as dramatic as that of the industrial revolution. To operate successfully, such systems must procure necessary raw materials from their surroundings. Therefore, next to automation, most critical for this new technology is the ability to extract important chemicals from readily available soils. In contrast to conventional metallurgical practice, these extraction processes cannot make substantial use of rare elements. We have designed a thermodynamically viable process and experimentally demonstrated most steps that differ from common practice. To this end we had to develop a small, disposable vacuum furnace system. Our work points to a viable extraction process.

  7. Photovoltaic Materials

    SciTech Connect

    Duty, C.; Angelini, J.; Armstrong, B.; Bennett, C.; Evans, B.; Jellison, G. E.; Joshi, P.; List, F.; Paranthaman, P.; Parish, C.; Wereszczak, A.

    2012-10-15

    The goal of the current project was to help make the US solar industry a world leader in the manufacture of thin film photovoltaics. The overall approach was to leverage ORNL’s unique characterization and processing technologies to gain a better understanding of the fundamental challenges for solar cell processing and apply that knowledge to targeted projects with industry members. ORNL has the capabilities in place and the expertise required to understand how basic material properties including defects, impurities, and grain boundaries affect the solar cell performance. ORNL also has unique processing capabilities to optimize the manufacturing process for fabrication of high efficiency and low cost solar cells. ORNL recently established the Center for Advanced Thin-film Systems (CATS), which contains a suite of optical and electrical characterization equipment specifically focused on solar cell research. Under this project, ORNL made these facilities available to industrial partners who were interested in pursuing collaborative research toward the improvement of their product or manufacturing process. Four specific projects were pursued with industrial partners: Global Solar Energy is a solar industry leader in full scale production manufacturing highly-efficient Copper Indium Gallium diSelenide (CIGS) thin film solar material, cells and products. ORNL worked with GSE to develop a scalable, non-vacuum, solution technique to deposit amorphous or nanocrystalline conducting barrier layers on untextured stainless steel substrates for fabricating high efficiency flexible CIGS PV. Ferro Corporation’s Electronic, Color and Glass Materials (“ECGM”) business unit is currently the world’s largest supplier of metallic contact materials in the crystalline solar cell marketplace. Ferro’s ECGM business unit has been the world's leading supplier of thick film metal pastes to the crystalline silicon PV industry for more than 30 years, and has had operational cells and

  8. PREFACE: Superconducting materials Superconducting materials

    NASA Astrophysics Data System (ADS)

    Charfi Kaddour, Samia; Singleton, John; Haddad, Sonia

    2011-11-01

    The discovery of superconductivity in 1911 was a great milestone in condensed matter physics. This discovery has resulted in an enormous amount of research activity. Collaboration among chemists and physicists, as well as experimentalists and theoreticians has given rise to very rich physics with significant potential applications ranging from electric power transmission to quantum information. Several superconducting materials have been synthesized. Crucial progress was made in 1987 with the discovery of high temperature superconductivity in copper-based compounds (cuprates) which have revealed new fascinating properties. Innovative theoretical tools have been developed to understand the striking features of cuprates which have remained for three decades the 'blue-eyed boy' for researchers in superconductor physics. The history of superconducting materials has been notably marked by the discovery of other compounds, particularly organic superconductors which despite their low critical temperature continue to attract great interest regarding their exotic properties. Last but not least, the recent observation of superconductivity in iron-based materials (pnictides) has renewed hope in reaching room temperature superconductivity. However, despite intense worldwide studies, several features related to this phenomenon remain unveiled. One of the fundamental key questions is the mechanism by which superconductivity takes place. Superconductors continue to hide their 'secret garden'. The new trends in the physics of superconductivity have been one of the two basic topics of the International Conference on Conducting Materials (ICoCoM2010) held in Sousse,Tunisia on 3-7 November 2010 and organized by the Tunisian Physical Society. The conference was a nice opportunity to bring together participants from multidisciplinary domains in the physics of superconductivity. This special section contains papers submitted by participants who gave an oral contribution at ICoCoM2010

  9. Superconducting materials

    SciTech Connect

    Ruvalds, J.

    1992-01-01

    Our research on high temperatures superconductors has produced novel insights for the normal state properties of copper oxides that have been discovered in the last few years. Advances in materials preparation have produced singly crystal samples, and sophisticated surface cleavage techniques have unveiled truly metallic behavior in many respects. Thus, the recent confirmation of a Fermi surface in several cuprate superconductors by photoemission spectroscopy has aroused interest in experimental features which heretofore were in apparent contrast to the expectations for a conventional Fermi Liquid. Our group has discovered that nested'' nearly parallel sections of the electron orbits yields an anomalous response which influences the electrical resistivity, optical reflectance, Raman spectrum, and neutron scattering cross section. Our analysis has provided an explanation for seemingly disparate experimental features of high temperature superconductors using consistent values for the electron-electron coupling and the plasma frequency. Our results include the following properties of high temperature superconductors: Nested Fermi Liquid Response in High Temperature Superconductors, Optical Reflectivity and Electron Energy Loss Data, Raman Spectra, Neutron Scattering Cross Section and Scaling, and Prospects for New Superconductors.

  10. Biointegrating Materials

    NASA Astrophysics Data System (ADS)

    Amédée, J.; Bordenave, L.; Durrieu, M.-C.; Fricain, J.-C.; Pothuaud, L.

    The extraordinary increase in human longevity explains the growing need for replacement organs. The remarkable successes of conventional transplants (associated with the development of effective antirejection drugs and improved control of their administration) are also accompanied by certain drawbacks. First on the list is an inadequate supply of replacement organs: the number of candidates for transplants grows larger, opposition to the removal of organs increases, and the number of transplants has reached a ceiling. Furthermore, it has come to light over the past few years that organ transplants carry a significant risk of transmitting pathogens. Finally, the main drawback lies in the need to pursue an immunosuppression treatment. Scientists and doctors have long been in search of alternatives to human organ transplants. According to the definition drawn up in Chester in 1986 at the Consensus Conference organised under the aegis of the European Society for Biomaterials, biomaterials are non-viable materials used in a medical device and destined to interact with biological systems, whether they contribute to the constitution of a diagnostic device, a tissue or organ substitute, or a device designed to provide functional assistance or replacement.

  11. Digestive Diseases Materials

    MedlinePlus

    ... NIDDK Health Information NIDDK Home NIDDK Image Library Digestive Disease, Nutrition, and Weight-control Materials Healthy eating, ... Materials Statistics Tip Sheets Catalog Home | Diabetes Materials | Digestive Diseases Materials | Kidney and Urologic Diseases Materials Online ...

  12. Critical Materials Institute

    ScienceCinema

    Alex King

    2016-07-12

    Ames Laboratory Director Alex King talks about the goals of the Critical Materials Institute in diversifying the supply of critical materials, developing substitute materials, developing tools and techniques for recycling critical materials, and forecasting materials needs to avoid future shortages.

  13. Critical Materials Institute

    SciTech Connect

    Alex King

    2013-01-09

    Ames Laboratory Director Alex King talks about the goals of the Critical Materials Institute in diversifying the supply of critical materials, developing substitute materials, developing tools and techniques for recycling critical materials, and forecasting materials needs to avoid future shortages.

  14. Gas storage materials, including hydrogen storage materials

    SciTech Connect

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2013-02-19

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  15. Gas storage materials, including hydrogen storage materials

    SciTech Connect

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2014-11-25

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material, such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  16. Geopolymer resin materials, geopolymer materials, and materials produced thereby

    DOEpatents

    Seo, Dong-Kyun; Medpelli, Dinesh; Ladd, Danielle; Mesgar, Milad

    2016-03-29

    A product formed from a first material including a geopolymer resin material, a geopolymer resin, or a combination thereof by contacting the first material with a fluid and removing at least some of the fluid to yield a product. The first material may be formed by heating and/or aging an initial geopolymer resin material to yield the first material before contacting the first material with the fluid. In some cases, contacting the first material with the fluid breaks up or disintegrates the first material (e.g., in response to contact with the fluid and in the absence of external mechanical stress), thereby forming particles having an external dimension in a range between 1 nm and 2 cm.

  17. Materials Project: A Materials Genome Approach

    DOE Data Explorer

    Ceder, Gerbrand [MIT; Persson, Kristin [LBNL

    Technological innovation - faster computers, more efficient solar cells, more compact energy storage - is often enabled by materials advances. Yet, it takes an average of 18 years to move new materials discoveries from lab to market. This is largely because materials designers operate with very little information and must painstakingly tweak new materials in the lab. Computational materials science is now powerful enough that it can predict many properties of materials before those materials are ever synthesized in the lab. By scaling materials computations over supercomputing clusters, this project has computed some properties of over 80,000 materials and screened 25,000 of these for Li-ion batteries. The computations predicted several new battery materials which were made and tested in the lab and are now being patented. By computing properties of all known materials, the Materials Project aims to remove guesswork from materials design in a variety of applications. Experimental research can be targeted to the most promising compounds from computational data sets. Researchers will be able to data-mine scientific trends in materials properties. By providing materials researchers with the information they need to design better, the Materials Project aims to accelerate innovation in materials research.[copied from http://materialsproject.org/about] You will be asked to register to be granted free, full access.

  18. Composite material dosimeters

    DOEpatents

    Miller, Steven D.

    1996-01-01

    The present invention is a composite material containing a mix of dosimeter material powder and a polymer powder wherein the polymer is transparent to the photon emission of the dosimeter material powder. By mixing dosimeter material powder with polymer powder, less dosimeter material is needed compared to a monolithic dosimeter material chip. Interrogation is done with excitation by visible light.

  19. Flat-plate solar array project. Volume 2: Silicon material

    NASA Technical Reports Server (NTRS)

    Lutwack, R.

    1986-01-01

    The goal of the Silicon Material Task, a part of the Flat Plate Solar Array (FSA) Project, was to develop and demonstate the technology for the low cost production of silicon of suitable purity to be used as the basic material for the manufacture of terrestrial photovoltaic solar cells. Summarized are 11 different processes for the production of silicon that were investigated and developed to varying extent by industrial, university, and Government researchers. The silane production section of the Union Carbide Corp. (UCC) silane process was developed completely in this program. Coupled with Siemens-type chemical vapor deposition reactors, the process was carried through the pilot stage. The overall UCC process involves the conversion of metallurgical-grade silicon to silane followed by decomposition of the silane to purified silicon. The other process developments are described to varying extents. Studies are reported on the effects of impurities in silicon on both silicon-material properties and on solar cell performance. These studies on the effects of impurities yielded extensive information and models for relating specific elemental concentrations to levels of deleterious effects.

  20. Method for forming materials

    DOEpatents

    Tolle, Charles R.; Clark, Denis E.; Smartt, Herschel B.; Miller, Karen S.

    2009-10-06

    A material-forming tool and a method for forming a material are described including a shank portion; a shoulder portion that releasably engages the shank portion; a pin that releasably engages the shoulder portion, wherein the pin defines a passageway; and a source of a material coupled in material flowing relation relative to the pin and wherein the material-forming tool is utilized in methodology that includes providing a first material; providing a second material, and placing the second material into contact with the first material; and locally plastically deforming the first material with the material-forming tool so as mix the first material and second material together to form a resulting material having characteristics different from the respective first and second materials.

  1. Materials Informatics: Fast Track to New Materials

    SciTech Connect

    Ferris, Kim F.; Peurrung, Loni M.; Marder, James M.

    2007-01-01

    Current methods for new materials development focus on either deeper fundamental-level studies or generation of large quantities of data. The data challenge in materials science is not only the volume of data being generated by many independent investigators, but its heterogeneity and also its complexity that must be transformed, analyzed, correlated and communicated. Materials informatics addresses these issues. Materials informatics is an emerging information-based field combining computational, statistical, and mathematical approaches with materials sciences for accelerating discovery and development of new materials. Within the informatic framework, the various different forms of information form a system architecture, an iterative cycle for transforming data into knowledge.

  2. Transporting particulate material

    DOEpatents

    Aldred, Derek Leslie; Rader, Jeffrey A.; Saunders, Timothy W.

    2011-08-30

    A material transporting system comprises a material transporting apparatus (100) including a material transporting apparatus hopper structure (200, 202), which comprises at least one rotary transporting apparatus; a stationary hub structure (900) constraining and assisting the at least one rotary transporting apparatus; an outlet duct configuration (700) configured to permit material to exit therefrom and comprising at least one diverging portion (702, 702'); an outlet abutment configuration (800) configured to direct material to the outlet duct configuration; an outlet valve assembly from the material transporting system venting the material transporting system; and a moving wall configuration in the material transporting apparatus capable of assisting the material transporting apparatus in transporting material in the material transporting system. Material can be moved from the material transporting apparatus hopper structure to the outlet duct configuration through the at least one rotary transporting apparatus, the outlet abutment configuration, and the outlet valve assembly.

  3. Introductory Materials Laboratory.

    ERIC Educational Resources Information Center

    Ritter, John E., Jr.

    Described is an introductory materials science laboratory program which emphasizes crystal structure both on the atomistic and microscopic scale and the dependence of materials properties on structure. The content of this program is classified into four major areas: (1) materials science, (2) mechanical behavior of materials, (3) materials testing…

  4. Nanocrystalline ceramic materials

    DOEpatents

    Siegel, Richard W.; Nieman, G. William; Weertman, Julia R.

    1994-01-01

    A method for preparing a treated nanocrystalline metallic material. The method of preparation includes providing a starting nanocrystalline metallic material with a grain size less than about 35 nm, compacting the starting nanocrystalline metallic material in an inert atmosphere and annealing the compacted metallic material at a temperature less than about one-half the melting point of the metallic material.

  5. Material efficiency: providing material services with less material production.

    PubMed

    Allwood, Julian M; Ashby, Michael F; Gutowski, Timothy G; Worrell, Ernst

    2013-03-13

    Material efficiency, as discussed in this Meeting Issue, entails the pursuit of the technical strategies, business models, consumer preferences and policy instruments that would lead to a substantial reduction in the production of high-volume energy-intensive materials required to deliver human well-being. This paper, which introduces a Discussion Meeting Issue on the topic of material efficiency, aims to give an overview of current thinking on the topic, spanning environmental, engineering, economics, sociology and policy issues. The motivations for material efficiency include reducing energy demand, reducing the emissions and other environmental impacts of industry, and increasing national resource security. There are many technical strategies that might bring it about, and these could mainly be implemented today if preferred by customers or producers. However, current economic structures favour the substitution of material for labour, and consumer preferences for material consumption appear to continue even beyond the point at which increased consumption provides any increase in well-being. Therefore, policy will be required to stimulate material efficiency. A theoretically ideal policy measure, such as a carbon price, would internalize the externality of emissions associated with material production, and thus motivate change directly. However, implementation of such a measure has proved elusive, and instead the adjustment of existing government purchasing policies or existing regulations-- for instance to do with building design, planning or vehicle standards--is likely to have a more immediate effect.

  6. Material efficiency: providing material services with less material production

    PubMed Central

    Allwood, Julian M.; Ashby, Michael F.; Gutowski, Timothy G.; Worrell, Ernst

    2013-01-01

    Material efficiency, as discussed in this Meeting Issue, entails the pursuit of the technical strategies, business models, consumer preferences and policy instruments that would lead to a substantial reduction in the production of high-volume energy-intensive materials required to deliver human well-being. This paper, which introduces a Discussion Meeting Issue on the topic of material efficiency, aims to give an overview of current thinking on the topic, spanning environmental, engineering, economics, sociology and policy issues. The motivations for material efficiency include reducing energy demand, reducing the emissions and other environmental impacts of industry, and increasing national resource security. There are many technical strategies that might bring it about, and these could mainly be implemented today if preferred by customers or producers. However, current economic structures favour the substitution of material for labour, and consumer preferences for material consumption appear to continue even beyond the point at which increased consumption provides any increase in well-being. Therefore, policy will be required to stimulate material efficiency. A theoretically ideal policy measure, such as a carbon price, would internalize the externality of emissions associated with material production, and thus motivate change directly. However, implementation of such a measure has proved elusive, and instead the adjustment of existing government purchasing policies or existing regulations— for instance to do with building design, planning or vehicle standards—is likely to have a more immediate effect. PMID:23359746

  7. Removal of Hazardous Pollutants from Wastewaters: Applications of TiO 2 -SiO 2 Mixed Oxide Materials

    DOE PAGES

    Rasalingam, Shivatharsiny; Peng, Rui; Koodali, Ranjit T.

    2014-01-01

    The direct release of untreated wastewaters from various industries and households results in the release of toxic pollutants to the aquatic environment. Advanced oxidation processes (AOP) have gained wide attention owing to the prospect of complete mineralization of nonbiodegradable organic substances to environmentally innocuous products by chemical oxidation. In particular, heterogeneous photocatalysis has been demonstrated to have tremendous promise in water purification and treatment of several pollutant materials that include naturally occurring toxins, pesticides, and other deleterious contaminants. In this work, we have reviewed the different removal techniques that have been employed for water purification. In particular, the applicationmore » of TiO 2 -SiO 2 binary mixed oxide materials for wastewater treatment is explained herein, and it is evident from the literature survey that these mixed oxide materials have enhanced abilities to remove a wide variety of pollutants.« less

  8. Thermoelectric materials and devices

    NASA Technical Reports Server (NTRS)

    Park, Yeonjoon (Inventor); Choi, Sang H. (Inventor); King, Glen C. (Inventor); Elliott, James R. (Inventor); Talcott, Noel A. (Inventor)

    2011-01-01

    New thermoelectric materials comprise highly [111]-oriented twinned group IV alloys on the basal plane of trigonal substrates, which exhibit a high thermoelectric figure of merit and good material performance, and devices made with these materials.

  9. Structural materials and components

    NASA Technical Reports Server (NTRS)

    Gagliani, John (Inventor); Lee, Raymond (Inventor)

    1982-01-01

    High density structural (blocking) materials composed of a polyimide filled with glass microballoons and methods for making such materials. Structural components such as panels which have integral edgings and/or other parts made of the high density materials.

  10. Immunohistochemistry staining for mismatch repair proteins: the endoscopic biopsy material provides useful and coherent results.

    PubMed

    Vilkin, Alex; Leibovici-Weissman, Ya'ara; Halpern, Marisa; Morgenstern, Sara; Brazovski, Eli; Gingold-Belfer, Rachel; Wasserberg, Nir; Brenner, Baruch; Niv, Yaron; Sneh-Arbib, Orly; Levi, Zohar

    2015-11-01

    Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) in patients with colorectal cancer can be performed on endoscopic biopsy material or the surgical resection material. Data are continuing to accumulate regarding the deleterious effect of neoadjuvant chemoradiation on MMRP expression. However, despite continuing rise in the use of endoscopic biopsies for IHC, most pathology departments still use mainly the surgical materials for IHC testing. In this study we compared the quality of stains among 96 colon cancer subjects with paired endoscopic and surgical material available for MLH1, MSH2, MSH6, and PMS2 stains (96 × 4, yielding 384 paired stains). Each slide received both a quantitative score (immunoreactivity [0-3] × percent positivity [0-4]) and a qualitative score (absent; weak and focal; strong). The quantitative scores of all MMRP were significantly higher among the endoscopic material (P<.001 for all). In 358 pairs (93.2%), both the endoscopic and operative material stained either strong (322, 83.9%) or absent (36, 9.4%). In 26 pairs (6.8%), the endoscopic material stained strong, whereas the operative material stained focal and weak. No endoscopic biopsy materials stained focal and weak. Our findings indicate that the biopsy material may provide more coherent results. Although these results may indicate that biopsy material provides coherent and useful results, it is yet to be determined if the demonstrated differences pose a real clinical problem in interpreting final results of IHC staining of such kind. Hence, we suggest that when available, the endoscopic material rather than the operative one should serve as the primary substrate for IHC staining.

  11. Pantoea agglomerans: a mysterious bacterium of evil and good. Part II--Deleterious effects: Dust-borne endotoxins and allergens--focus on grain dust, other agricultural dusts and wood dust.

    PubMed

    Dutkiewicz, Jacek; Mackiewicz, Barbara; Lemieszek, Marta Kinga; Golec, Marcin; Skórska, Czesława; Góra-Florek, Anna; Milanowski, Janusz

    2016-01-01

    Pantoea agglomerans, a Gram-negative bacterium developing in a variety of plants as epiphyte or endophyte is particularly common in grain and grain dust, and has been identified by an interdisciplinary group from Lublin, eastern Poland, as a causative agent of work-related diseases associated with exposure to grain dust and other agricultural dusts. The concentration of P. agglomerans in grain as well as in the settled grain and flour dust was found to be high, ranging from 10(4)-10(8) CFU/g, while in the air polluted with grain or flour dust it ranged from 10(3)-10(5) CFU/m(3) and formed 73.2-96% of the total airborne Gram-negative bacteria. The concentration of P. agglomerans was also relatively high in the air of the facilities processing herbs and other plant materials, while it was lower in animal farms and in wood processing facilities. Pantoea agglomerans produces a biologically-potent endotoxin (cell wall lipopolysaccharide, LPS). The significant part of this endotoxin occurs in dusts in the form of virus-sized globular nanoparticles measuring 10-50 nm that could be described as the 'endotoxin super-macromolecules'. A highly significant relationship was found (R=0.804, P=0.000927) between the concentration of the viable P. agglomerans in the air of various agricultural and wood industry settings and the concentration of bacterial endotoxin in the air, as assessed by the Limulus test. Although this result may be interfered by the presence of endotoxin produced by other Gram-negative species, it unequivocally suggests the primary role of the P. agglomerans endotoxin as an adverse agent in the agricultural working environment, causing toxic pneumonitis (ODTS). Numerous experiments by the inhalation exposure of animals to various extracts of P. agglomerans strains isolated from grain dust, including endotoxin isolated with trichloroacetic acid (LPS-TCA), endotoxin nanoparticles isolated in sucrose gradient (VECN), and mixture of proteins and endotoxin obtained

  12. Pantoea agglomerans: a mysterious bacterium of evil and good. Part II--Deleterious effects: Dust-borne endotoxins and allergens--focus on grain dust, other agricultural dusts and wood dust.

    PubMed

    Dutkiewicz, Jacek; Mackiewicz, Barbara; Lemieszek, Marta Kinga; Golec, Marcin; Skórska, Czesława; Góra-Florek, Anna; Milanowski, Janusz

    2016-01-01

    Pantoea agglomerans, a Gram-negative bacterium developing in a variety of plants as epiphyte or endophyte is particularly common in grain and grain dust, and has been identified by an interdisciplinary group from Lublin, eastern Poland, as a causative agent of work-related diseases associated with exposure to grain dust and other agricultural dusts. The concentration of P. agglomerans in grain as well as in the settled grain and flour dust was found to be high, ranging from 10(4)-10(8) CFU/g, while in the air polluted with grain or flour dust it ranged from 10(3)-10(5) CFU/m(3) and formed 73.2-96% of the total airborne Gram-negative bacteria. The concentration of P. agglomerans was also relatively high in the air of the facilities processing herbs and other plant materials, while it was lower in animal farms and in wood processing facilities. Pantoea agglomerans produces a biologically-potent endotoxin (cell wall lipopolysaccharide, LPS). The significant part of this endotoxin occurs in dusts in the form of virus-sized globular nanoparticles measuring 10-50 nm that could be described as the 'endotoxin super-macromolecules'. A highly significant relationship was found (R=0.804, P=0.000927) between the concentration of the viable P. agglomerans in the air of various agricultural and wood industry settings and the concentration of bacterial endotoxin in the air, as assessed by the Limulus test. Although this result may be interfered by the presence of endotoxin produced by other Gram-negative species, it unequivocally suggests the primary role of the P. agglomerans endotoxin as an adverse agent in the agricultural working environment, causing toxic pneumonitis (ODTS). Numerous experiments by the inhalation exposure of animals to various extracts of P. agglomerans strains isolated from grain dust, including endotoxin isolated with trichloroacetic acid (LPS-TCA), endotoxin nanoparticles isolated in sucrose gradient (VECN), and mixture of proteins and endotoxin obtained

  13. Importing biological materials.

    PubMed

    Wolf, P

    2001-05-01

    This overview discusses critical issues regarding importing of restricted biological materials along with criteria for handling these materials. Guidelines for importing non-restricted biological materials are also covered. Recommendations are given for packaging biological materials for export, and finally, the necessary steps for obtaining an import permit application are outlined. PMID:18429071

  14. Coated ceramic breeder materials

    DOEpatents

    Tam, Shiu-Wing; Johnson, Carl E.

    1987-04-07

    A breeder material for use in a breeder blanket of a nuclear reactor is disclosed. The breeder material comprises a core material of lithium containing ceramic particles which has been coated with a neutron multiplier such as Be or BeO, which coating has a higher thermal conductivity than the core material.

  15. Coated ceramic breeder materials

    DOEpatents

    Tam, Shiu-Wing; Johnson, Carl E.

    1987-01-01

    A breeder material for use in a breeder blanket of a nuclear reactor is disclosed. The breeder material comprises a core material of lithium containing ceramic particles which has been coated with a neutron multiplier such as Be or BeO, which coating has a higher thermal conductivity than the core material.

  16. Biological materials by design.

    PubMed

    Qin, Zhao; Dimas, Leon; Adler, David; Bratzel, Graham; Buehler, Markus J

    2014-02-19

    In this topical review we discuss recent advances in the use of physical insight into the way biological materials function, to design novel engineered materials 'from scratch', or from the level of fundamental building blocks upwards and by using computational multiscale methods that link chemistry to material function. We present studies that connect advances in multiscale hierarchical material structuring with material synthesis and testing, review case studies of wood and other biological materials, and illustrate how engineered fiber composites and bulk materials are designed, modeled, and then synthesized and tested experimentally. The integration of experiment and simulation in multiscale design opens new avenues to explore the physics of materials from a fundamental perspective, and using complementary strengths from models and empirical techniques. Recent developments in this field illustrate a new paradigm by which complex material functionality is achieved through hierarchical structuring in spite of simple material constituents. PMID:24451343

  17. Materials Analysis and Modeling of Underfill Materials.

    SciTech Connect

    Wyatt, Nicholas B; Chambers, Robert S.

    2015-08-01

    The thermal-mechanical properties of three potential underfill candidate materials for PBGA applications are characterized and reported. Two of the materials are a formulations developed at Sandia for underfill applications while the third is a commercial product that utilizes a snap-cure chemistry to drastically reduce cure time. Viscoelastic models were calibrated and fit using the property data collected for one of the Sandia formulated materials. Along with the thermal-mechanical analyses performed, a series of simple bi-material strip tests were conducted to comparatively analyze the relative effects of cure and thermal shrinkage amongst the materials under consideration. Finally, current knowledge gaps as well as questions arising from the present study are identified and a path forward presented.

  18. Puncture detecting barrier materials

    DOEpatents

    Hermes, Robert E.; Ramsey, David R.; Stampfer, Joseph F.; Macdonald, John M.

    1998-01-01

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material.

  19. Nanocrystalline ceramic materials

    DOEpatents

    Siegel, R.W.; Nieman, G.W.; Weertman, J.R.

    1994-06-14

    A method is disclosed for preparing a treated nanocrystalline metallic material. The method of preparation includes providing a starting nanocrystalline metallic material with a grain size less than about 35 nm, compacting the starting nanocrystalline metallic material in an inert atmosphere and annealing the compacted metallic material at a temperature less than about one-half the melting point of the metallic material. 19 figs.

  20. Puncture detecting barrier materials

    DOEpatents

    Hermes, R.E.; Ramsey, D.R.; Stampfer, J.F.; Macdonald, J.M.

    1998-03-31

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material. 4 figs.

  1. Joining of dissimilar materials

    DOEpatents

    Tucker, Michael C; Lau, Grace Y; Jacobson, Craig P

    2012-10-16

    A method of joining dissimilar materials having different ductility, involves two principal steps: Decoration of the more ductile material's surface with particles of a less ductile material to produce a composite; and, sinter-bonding the composite produced to a joining member of a less ductile material. The joining method is suitable for joining dissimilar materials that are chemically inert towards each other (e.g., metal and ceramic), while resulting in a strong bond with a sharp interface between the two materials. The joining materials may differ greatly in form or particle size. The method is applicable to various types of materials including ceramic, metal, glass, glass-ceramic, polymer, cermet, semiconductor, etc., and the materials can be in various geometrical forms, such as powders, fibers, or bulk bodies (foil, wire, plate, etc.). Composites and devices with a decorated/sintered interface are also provided.

  2. Enhanced magnetocaloric effect material

    DOEpatents

    Lewis, Laura J. H.

    2006-07-18

    A magnetocaloric effect heterostructure having a core layer of a magnetostructural material with a giant magnetocaloric effect having a magnetic transition temperature equal to or greater than 150 K, and a constricting material layer coated on at least one surface of the magnetocaloric material core layer. The constricting material layer may enhance the magnetocaloric effect by restriction of volume changes of the core layer during application of a magnetic field to the heterostructure. A magnetocaloric effect heterostructure powder comprising a plurality of core particles of a magnetostructural material with a giant magnetocaloric effect having a magnetic transition temperature equal to or greater than 150 K, wherein each of the core particles is encapsulated within a coating of a constricting material is also disclosed. A method for enhancing the magnetocaloric effect within a giant magnetocaloric material including the step of coating a surface of the magnetocaloric material with a constricting material is disclosed.

  3. Martian surface materials

    NASA Technical Reports Server (NTRS)

    Moore, H. J.

    1991-01-01

    A semiquantitative appreciation for the physical properties of the Mars surface materials and their global variations can be gained from the Viking Lander and remote sensing observations. Analyses of Lander data yields estimates of the mechanical properties of the soil-like surface materials and best guess estimates can be made for the remote sensing signatures of the soil-like materials at the landing sites. Results show that significant thickness of powderlike surface materials with physical properties similar to drift material are present on Mars and probably pervasive in the Tharsis region. It also appears likely that soil-like materials similar to crusty to cloddy material are typical for Mars, and that soil-like material similar to blocky material are common on Mars.

  4. Orbital foamed material extruder

    NASA Technical Reports Server (NTRS)

    Tucker, Dennis S. (Inventor)

    2009-01-01

    This invention is a process for producing foamed material in space comprising the steps of: rotating the material to simulate the force of gravity; heating the rotating material until it is molten; extruding the rotating, molten material; injecting gas into the extruded, rotating, molten material to produce molten foamed material; allowing the molten foamed material to cool to below melting temperature to produce the foamed material. The surface of the extruded foam may be heated to above melting temperature and allowed to cool to below melting temperature. The extruded foam may also be cut to predetermined length. The starting material may be metal or glass. Heating may be accomplished by electrical heating elements or by solar heating.

  5. Smart Materials 1

    SciTech Connect

    Martin, Peter M.

    2003-06-01

    What is a smart material? What makes it smarter than a passive ''dumb'' material? The term ''smart material'' means a lot of things to a lot of people. ''Adaptronics'' is a word also commonly used for smart materials. One common definition is based on a technology paradigm: the integration of actuators, sensors, and controls with a material or structural component. The second broad definition is oriented more to biological systems: material systems that have intelligence and life features integrated in the microstructure of the material system to reduce mass energy and produce adaptive functionality. My basic simple-minded definition is: a ''smart material'' is a general term for a broad category of multifunctional materials for which a specific property (optical, mechanical, electronic, etc.) can be controllably modified.

  6. Green materials science and engineering reduces biofouling: approaches for medical and membrane-based technologies

    PubMed Central

    Dobosz, Kerianne M.; Kolewe, Kristopher W.; Schiffman, Jessica D.

    2015-01-01

    Numerous engineered and natural environments suffer deleterious effects from biofouling and/or biofilm formation. For instance, bacterial contamination on biomedical devices pose serious health concerns. In membrane-based technologies, such as desalination and wastewater reuse, biofouling decreases membrane lifetime, and increases the energy required to produce clean water. Traditionally, approaches have combatted bacteria using bactericidal agents. However, due to globalization, a decline in antibiotic discovery, and the widespread resistance of microbes to many commercial antibiotics and metallic nanoparticles, new materials, and approaches to reduce biofilm formation are needed. In this mini-review, we cover the recent strategies that have been explored to combat microbial contamination without exerting evolutionary pressure on microorganisms. Renewable feedstocks, relying on structure-property relationships, bioinspired/nature-derived compounds, and green processing methods are discussed. Greener strategies that mitigate biofouling hold great potential to positively impact human health and safety. PMID:25852659

  7. Green materials science and engineering reduces biofouling: approaches for medical and membrane-based technologies.

    PubMed

    Dobosz, Kerianne M; Kolewe, Kristopher W; Schiffman, Jessica D

    2015-01-01

    Numerous engineered and natural environments suffer deleterious effects from biofouling and/or biofilm formation. For instance, bacterial contamination on biomedical devices pose serious health concerns. In membrane-based technologies, such as desalination and wastewater reuse, biofouling decreases membrane lifetime, and increases the energy required to produce clean water. Traditionally, approaches have combatted bacteria using bactericidal agents. However, due to globalization, a decline in antibiotic discovery, and the widespread resistance of microbes to many commercial antibiotics and metallic nanoparticles, new materials, and approaches to reduce biofilm formation are needed. In this mini-review, we cover the recent strategies that have been explored to combat microbial contamination without exerting evolutionary pressure on microorganisms. Renewable feedstocks, relying on structure-property relationships, bioinspired/nature-derived compounds, and green processing methods are discussed. Greener strategies that mitigate biofouling hold great potential to positively impact human health and safety.

  8. Synthesis and Characterization of Polyphosphazene Materials for Advanced Lithium-Water Batteries

    SciTech Connect

    Mason K. Harrup; Thomas A. Luther; Frederick F. Stewart; Christopher J. Orme; Mark L. Stone; William F. Bauer

    2007-08-01

    Development of long-lived high-energy lithium-water batteries hinges upon developing solid polymer electrolytes (SPEs) with the appropriate properties. These polymer membranes paradoxically must allow lithium atoms to pass from the metallic surface, oxidize to the ionic form, and then pass through the membrane to the water outside. At the same time, the membrane must exclude all water, tramp ions, and deleterious gases such as oxygen and carbon dioxide. SPE membranes are the leading choice for lithium-water batteries however, because current non-membrane approaches being pursued by other research groups suffer from two insurmountable problems - storage and non-productive energy loss via direct lithium/water reaction. In this paper, we present the results of our latest investigations into the transport of water and permanent gasses, such as carbon dioxide, through polyphosphazene SPE materials designed to address the challenges inherent in lithium water batteries.

  9. [Elastomeric impression materials].

    PubMed

    Anagnostopoulos, T; Tsokas, K

    1990-01-01

    A review of the literature on elastomeric impression materials, is presented in this paper. The article mentions the composition and the most important properties of the elastomeric impression materials used in dental practice. The clinical significance of these materials, physical and mechanical properties are also emphasized. In addition some new elastomeric impression materials with improved properties and a new (experimental) light-cured impression material, are mentioned. Another part of this article is the biocompatibility of these materials. In the end the great significance of handling is outlined. PMID:2130039

  10. Materials for breeding blankets

    SciTech Connect

    Mattas, R.F.; Billone, M.C.

    1995-09-01

    There are several candidate concepts for tritium breeding blankets that make use of a number of special materials. These materials can be classified as Primary Blanket Materials, which have the greatest influence in determining the overall design and performance, and Secondary Blanket Materials, which have key functions in the operation of the blanket but are less important in establishing the overall design and performance. The issues associated with the blanket materials are specified and several examples of materials performance are given. Critical data needs are identified.

  11. Materials All Around Us

    NASA Technical Reports Server (NTRS)

    Jacobs, James A.

    1996-01-01

    The purpose of this journal exercise is to determine the properties of the materials in the environment around us, and to relate these properties to the materials systems for which they are used. Students will develop a strong rationale for gaining knowledge of engineering materials. The journal entries will serve as a starting point classroom discussion. Along with the journal, students are required to bring samples to class of 'found' materials and products composed of materials systems. Students are encouraged to be materials observers.

  12. Insulated waterproof drainage material

    SciTech Connect

    Tarko, P.L.

    1988-03-15

    An insulative waterproof drainage material is described comprising: a sheet of rigid material having hills and valleys therein to define a core having opposed surfaces; permeable fabric material attached to one of the opposed surfaces; and a layer of thermally insulative material on the other of the opposed surfaces. The insulative material has first surface covering the hills and valleys and a second surface oppositely disposed from the first surface defining an outer surface. The outer surface is spaced a preselected distance D from the hills of the core. The pre-selected distance D define an insulative material thickness corresponding to a pre-selected thermal value.

  13. Materials science and engineering

    SciTech Connect

    Lesuer, D.R.

    1997-02-01

    During FY-96, work within the Materials Science and Engineering Thrust Area was focused on material modeling. Our motivation for this work is to develop the capability to study the structural response of materials as well as material processing. These capabilities have been applied to a broad range of problems, in support of many programs at Lawrence Livermore National Laboratory. These studies are described in (1) Strength and Fracture Toughness of Material Interfaces; (2) Damage Evolution in Fiber Composite Materials; (3) Flashlamp Envelope Optical Properties and Failure Analysis; (4) Synthesis and Processing of Nanocrystalline Hydroxyapatite; and (5) Room Temperature Creep Compliance of Bulk Kel-E.

  14. Nondestructive material characterization

    DOEpatents

    Deason, Vance A.; Johnson, John A.; Telschow, Kenneth L.

    1991-01-01

    A method and apparatus for nondestructive material characterization, such as identification of material flaws or defects, material thickness or uniformity and material properties such as acoustic velocity. The apparatus comprises a pulsed laser used to excite a piezoelectric (PZ) transducer, which sends acoustic waves through an acoustic coupling medium to the test material. The acoustic wave is absorbed and thereafter reflected by the test material, whereupon it impinges on the PZ transducer. The PZ transducer converts the acoustic wave to electrical impulses, which are conveyed to a monitor.

  15. Materials Test Branch

    NASA Technical Reports Server (NTRS)

    Gordon, Gail

    2012-01-01

    The Materials Test Branch resides at Marshall Space Flight Center's Materials and Processing laboratory and has a long history of supporting NASA programs from Mercury to the recently retired Space Shuttle. The Materials Test Branch supports its customers by supplying materials testing expertise in a wide range of applications. The Materials Test Branch is divided into three Teams, The Chemistry Team, The Tribology Team and the Mechanical Test Team. Our mission and goal is to provide world-class engineering excellence in materials testing with a special emphasis on customer service.

  16. Materials Discovery: Informatic Strategies for Optical Materials

    SciTech Connect

    Ferris, Kim F.; Webb-Robertson, Bobbie-Jo M.; Jones, Dumont M.

    2007-01-15

    Information-based materials discovery offers a structured method to evolve materials signatures based upon their physical properties, and to direct searches using performance-based criteria. In this current paper, we focus on the crystal structure aspects of an optical material and construct an information-based model to determine the proclivity of a particular AB composition to exhibit multiple crystal system behavior. Exploratory data methods used both supervised (support-vector machines) and unsupervised (disorder-reduction and principal-component) classification methods for structural signature development; revealing complementary valid signatures. Examination of the relative contributions of the materials chemistry descriptors within these signatures indicates a strong role for Mendeleev number chemistry which must be balanced against the cationic/anionic radius ratio and electronegativity differences of constituents within the unit cell.

  17. Materials science and engineering

    SciTech Connect

    Lesuer, D R

    1998-01-01

    During FY-97, work within the Materials Science and Engineering thrust area was focused on material modeling. Their motivation for this work is to develop the capability to study the structural response of materials as well as materials processing. These capabilities have been applied to a broad range of problems, which support many programs at Lawrence Livermore National Laboratory. Recent examples of structural response problems studied include material fracture (such as interface failure), damage in laser optics, the response of weapons components (such as high explosives) and the failure of composite materials. For materials processing, typical problems studied include metal forming, laser processing, casting, and heat treating. To improve our ability to model material behavior, much of the work involves developing new material models and failure models, as well as applying the codes to new problems. Most investigations involve experimental studies to gather basic information on material response and to validate codes or material models. Projects are inherently multi-disciplinary, involving several investigators with expertise in materials and mechanics. The thrust area studies for FY-97 are described in the following three articles: (1) Evolution of Anisotropic Yield Behavior; (2) Modeling of She Localization in Materials; and (3) Modeling of Casting Microstructures and Defects.

  18. EC Transmission Line Materials

    SciTech Connect

    Bigelow, Tim S

    2012-05-01

    The purpose of this document is to identify materials acceptable for use in the US ITER Project Office (USIPO)-supplied components for the ITER Electron cyclotron Heating and Current Drive (ECH&CD) transmission lines (TL), PBS-52. The source of material property information for design analysis shall be either the applicable structural code or the ITER Material Properties Handbook. In the case of conflict, the ITER Material Properties Handbook shall take precedence. Materials selection, and use, shall follow the guidelines established in the Materials Assessment Report (MAR). Materials exposed to vacuum shall conform to the ITER Vacuum Handbook. [Ref. 2] Commercial materials shall conform to the applicable standard (e.g., ASTM, JIS, DIN) for the definition of their grade, physical, chemical and electrical properties and related testing. All materials for which a suitable certification from the supplier is not available shall be tested to determine the relevant properties, as part of the procurement. A complete traceability of all the materials including welding materials shall be provided. Halogenated materials (example: insulating materials) shall be forbidden in areas served by the detritiation systems. Exceptions must be approved by the Tritium System and Safety Section Responsible Officers.

  19. Silicone azide fireproof material

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Finely powdered titanium oxide was added to silicone azide as the sintering agent to produce a nonflammable material. Mixing proportions, physical properties, and chemical composition of the fireproofing material are included.

  20. Lightweight Materials & Structures

    NASA Video Gallery

    The Lightweight Materials and Structures (LMS) project will mature high-payoff structures and materials technologies that have direct application to NASA’s future space exploration needs.One of the...

  1. Supplements to Textbook Materials.

    ERIC Educational Resources Information Center

    Holmes, Ken

    1994-01-01

    Describes the many kinds of materials that English teachers can draw upon to enrich and expand students' experiences with literature. Outlines ancillary materials used to supplement the study of William Shakespeare's "Julius Caesar." (HB)

  2. Renewable smart materials

    NASA Astrophysics Data System (ADS)

    Kim, Hyun Chan; Mun, Seongcheol; Ko, Hyun-U.; Zhai, Lindong; Kafy, Abdullahil; Kim, Jaehwan

    2016-07-01

    The use of renewable materials is essential in future technologies to harmonize with our living environment. Renewable materials can maintain our resources from the environment so as to overcome degradation of natural environmental services and diminished productivity. This paper reviews recent advancement of renewable materials for smart material applications, including wood, cellulose, chitin, lignin, and their sensors, actuators and energy storage applications. To further improve functionality of renewable materials, hybrid composites of inorganic functional materials are introduced by incorporating carbon nanotubes, titanium dioxide and tin oxide conducting polymers and ionic liquids. Since renewable materials have many advantages of biocompatible, sustainable, biodegradable, high mechanical strength and versatile modification behaviors, more research efforts need to be focused on the development of renewable smart materials.

  3. Materials processing in space

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The feasibility and possible advantages of processing materials in a nongravitational field are considered. Areas of investigation include biomedical applications, the processing of inorganic materials, and flight programs and funding.

  4. Materials modelling in London

    NASA Astrophysics Data System (ADS)

    Ciudad, David

    2016-04-01

    Angelos Michaelides, Professor in Theoretical Chemistry at University College London (UCL) and co-director of the Thomas Young Centre (TYC), explains to Nature Materials the challenges in materials modelling and the objectives of the TYC.

  5. Bibliography of AV Materials.

    ERIC Educational Resources Information Center

    Friedstein, Harriet, Ed.

    1981-01-01

    Lists commercially available audiovisual materials by subject area. Includes title, producer (addresses given), catalog number, format (film, filmstrip, cassette, slides), and prices. Subject areas include: elements; equilibrium; gases; laboratory techniques and experiments; general chemistry; introductory materials (including mathematics); and…

  6. Nanostructured composite reinforced material

    DOEpatents

    Seals, Roland D.; Ripley, Edward B.; Ludtka, Gerard M.

    2012-07-31

    A family of materials wherein nanostructures and/or nanotubes are incorporated into a multi-component material arrangement, such as a metallic or ceramic alloy or composite/aggregate, producing a new material or metallic/ceramic alloy. The new material has significantly increased strength, up to several thousands of times normal and perhaps substantially more, as well as significantly decreased weight. The new materials may be manufactured into a component where the nanostructure or nanostructure reinforcement is incorporated into the bulk and/or matrix material, or as a coating where the nanostructure or nanostructure reinforcement is incorporated into the coating or surface of a "normal" substrate material. The nanostructures are incorporated into the material structure either randomly or aligned, within grains, or along or across grain boundaries.

  7. Bridged graphite oxide materials

    NASA Technical Reports Server (NTRS)

    Herrera-Alonso, Margarita (Inventor); McAllister, Michael J. (Inventor); Aksay, Ilhan A. (Inventor); Prud'homme, Robert K. (Inventor)

    2010-01-01

    Bridged graphite oxide material comprising graphite sheets bridged by at least one diamine bridging group. The bridged graphite oxide material may be incorporated in polymer composites or used in adsorption media.

  8. Structural materials and components

    NASA Technical Reports Server (NTRS)

    Gagliani, John (Inventor); Lee, Raymond (Inventor)

    1982-01-01

    High density structural (blocking) materials composed of a polyimide filled with glass microballoons. Structural components such as panels which have integral edgings and/or other parts made of the high density materials.

  9. Structural materials and components

    NASA Technical Reports Server (NTRS)

    Gagliani, John (Inventor); Lee, Raymond (Inventor)

    1983-01-01

    High density structural (blocking) materials composed of a polyimide filled with glass microballoons. Structural components such as panels which have integral edgings and/or other parts made of the high density materials.

  10. Improvisation: Teaching Materials.

    ERIC Educational Resources Information Center

    Kuzmich, John A., Jr.

    1980-01-01

    The past, present and future of music improvisation is discussed. Resources for piano, guitar, elementary general music materials, and electronic music materials are included, along with addresses of publishers. The emphasis is on jazz. (KC)

  11. Materials Genome Initiative Element

    NASA Technical Reports Server (NTRS)

    Vickers, John

    2015-01-01

    NASA is committed to developing new materials and manufacturing methods that can enable new missions with ever increasing mission demands. Typically, the development and certification of new materials and manufacturing methods in the aerospace industry has required more than 20 years of development time with a costly testing and certification program. To reduce the cost and time to mature these emerging technologies, NASA is developing computational materials tools to improve understanding of the material and guide the certification process.

  12. Smart materials and structures

    NASA Technical Reports Server (NTRS)

    Rogowski, Robert S.; Heyman, Joseph S.

    1993-01-01

    Embedded optical fibers allow not only the cure-monitoring and in-service lifetime measurements of composite materials, but the NDE of material damage and degradation with aging. The capabilities of such damage-detection systems have been extended to allow the quantitative determination of 2D strain in materials by several different methods, including the interferometric and the numerical. It remains to be seen, what effect the embedded fibers have on the strength of the 'smart' materials created through their incorporation.

  13. Biomimetics and smart materials

    NASA Astrophysics Data System (ADS)

    Simmons, Wilbur C.

    1997-11-01

    Smart materials functions often mimic biological functions. Recent basic research at the U.S. Army Research Office has focused on biomimetics and meso-scale smart materials. Current ARO materials research interests and progress in these areas are reviewed for sensors, molecular recognition, signal transduction, structures and control functions.

  14. Biomimetics and smart materials

    NASA Astrophysics Data System (ADS)

    Simmons, Wilbur C.

    1997-11-01

    Smart Materials functions often mimic biological functions. Recent basic research at the US Army Research Office has focused on biomimetrics and meso-scale smart materials. Current ARO materials research interests and progress in these areas will be reviewed for sensors, molecular recognition, signal transduction, structures and control functions.

  15. Energy Education Materials Bibliography.

    ERIC Educational Resources Information Center

    Minnesota State Energy Agency, St. Paul.

    This is an annotated bibliography of selected energy education materials. The materials included in this document are indexed according to grade level and according to whether they are background materials or classroom activities. Each of the 100 items listed were evaluated and included into either the "A" list or the "B" list. The "A" list…

  16. Advanced Materials Technology

    NASA Technical Reports Server (NTRS)

    Blankenship, C. P. (Compiler); Teichman, L. A. (Compiler)

    1982-01-01

    Composites, polymer science, metallic materials (aluminum, titanium, and superalloys), materials processing technology, materials durability in the aerospace environment, ceramics, fatigue and fracture mechanics, tribology, and nondestructive evaluation (NDE) are discussed. Research and development activities are introduced to the nonaerospace industry. In order to provide a convenient means to help transfer aerospace technology to the commercial mainstream in a systematic manner.

  17. Creating Quality Media Materials.

    ERIC Educational Resources Information Center

    Hortin, John A.; Bailey, Gerald D.

    1982-01-01

    Innovation, imagination, and student creativity are key ingredients in creating quality media materials for the small school. Student-produced media materials, slides without a camera, personalized slide programs and copy work, self-made task cards, self-made overhead transparencies, graphic materials, and utilization of the mass media are some of…

  18. Bibliography of Citizenship Materials

    ERIC Educational Resources Information Center

    CASAS - Comprehensive Adult Student Assessment Systems (NJ1), 2008

    2008-01-01

    The 2008 CASAS "Bibliography of Citizenship Materials" lists available instructional resources for citizenship education. It focuses on materials appropriate for preparing people for the naturalization process and the standardized citizenship examination. Resources include textbooks, audio materials, software and Videos/DVDs. The bibliography also…

  19. Paramagnetic and Diamagnetic Materials

    ERIC Educational Resources Information Center

    Thompson, Frank

    2011-01-01

    Paramagnetic and diamagnetic materials are now generally known as the "Cinderella" materials of the magnetic world. However, susceptibility measurements made on these materials in the past have revealed many details about the molecular bonding and the atomic structure of the so-called "transition" elements. Indeed, the magnetic moment of neodymium…

  20. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  1. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  2. Advanced neutron absorber materials

    DOEpatents

    Branagan, Daniel J.; Smolik, Galen R.

    2000-01-01

    A neutron absorbing material and method utilizing rare earth elements such as gadolinium, europium and samarium to form metallic glasses and/or noble base nano/microcrystalline materials, the neutron absorbing material having a combination of superior neutron capture cross sections coupled with enhanced resistance to corrosion, oxidation and leaching.

  3. Fusion reactor materials

    SciTech Connect

    none,

    1989-01-01

    This paper discuses the following topics on fusion reactor materials: irradiation, facilities, test matrices, and experimental methods; dosimetry, damage parameters, and activation calculations; materials engineering and design requirements; fundamental mechanical behavior; radiation effects; development of structural alloys; solid breeding materials; and ceramics.

  4. THE INSTRUCTIONAL MATERIALS CENTER.

    ERIC Educational Resources Information Center

    ARTZ, DELPHINE; AND OTHERS

    THIS BULLETIN PRESENTS RECOMMENDATIONS WITH REGARD TO PROGRAM, PERSONNEL, AND FACILITIES FOR AN INSTRUCTIONAL MATERIALS CENTER. IT INCLUDES UTILIZATION, MATERIALS, FACILITIES, ORGANIZATION AND LAYOUTS FOR AN INSTRUCTIONAL MATERIALS CENTER. CASE STUDIES AND EXAMPLES ARE PROVIDED FOR MAKING THE MAXIMUM POSSIBLE USAGE OF THE CENTER WITHIN BOTH THE…

  5. Materials for Space Exploration

    NASA Technical Reports Server (NTRS)

    Robertson, Luke B.; Williams, Martha

    2010-01-01

    Topics include a lab overview, testing and processing equipment, hemochromic hydrogen sensors, antimicrobial materials, wire system materials, CNT ink formulations, CNT ink dust screens, CNT ink printed circuitry, cryogenic materials development, fire and polymers, the importance of lighting, electric lighting systems, LED for plant growth, and carbon nanotube fiber filaments.

  6. A study of possible deleterious effects of consanguinity.

    PubMed

    Abdulrazzaq, Y M; Bener, A; al-Gazali, L I; al-Khayat, A I; Micallef, R; Gaber, T

    1997-03-01

    The aim of the study was to determine whether consanguineous marriages result in reproductive wastage and an increased incidence of illness in the offspring in a community with a long history of inbreeding and an expected high rate of consanguineous marriage. A representative sample of 2200 women aged > or = 15 years from Dubai and Al Ain, two cities in the United Arab Emirates, representing on the one hand a modern metropolis and on the other a traditional society, were studied. A questionnaire, which included questions on age, parity, gravidity, number of stillbirths, number of abortions, number of children alive, neonatal deaths and specific illnesses in children, was administered by nurses in antenatal and gynaecological clinics in the two cities. The rate of consanguineous marriage was 50.5% and parity, gravidity, ages and number of children were similar in consanguineous and non-consanguineous groups. There was no significant difference in rates of abortion, stillbirth and neonatal death between the two groups. Overall, there was statistically significant higher reproductive wastage in consanguineous couples, but when the category of less than second cousins was excluded from the consanguineous group no difference was found in reproductive wastage between consanguineous and non-consanguineous marriages. Children born to consanguineous unions also had significantly higher incidences of illnesses (37.1%) than those of non-consanguineous unions (29%). The occurrence of malignancies, congenital abnormalities, mental retardation and physical handicap was significantly higher in offspring of consanguineous than non-consanguineous marriages. In conclusion, consanguinity did not result in reproductive wastage, but was found to be an important factor in the causation of specific illnesses in offspring.

  7. Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A

    PubMed Central

    Klarić, Maja Šegvić; Rašić, Dubravka; Peraica, Maja

    2013-01-01

    Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than one mycotoxin, earlier studies focused on the occurrence and toxicology of only OTA. Only a limited number of surveys showed that OTA co-occurs in food with mycotoxins (citrinin-CIT, penicilic acid, fumonisin B1-FB1, aflatoxins-AF) which exert nephrotoxic, carcinogenic or carcinogen-promoting activity. This review summarises the findings on OTA and its co-occurrence with the mentioned mycotoxins in food as well as experimental data on their combined toxicity. Most of the tested mycotoxin mixtures involving OTA produced additive or synergistic effects in experimental models suggesting that these combinations represent a significant health hazard. Special attention should be given to mixtures that include carcinogenic and cancer-promoting mycotoxins. PMID:24189375

  8. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids.

    PubMed

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas' disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts' immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host's immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  9. Deleterious effects of magnesium intoxication upon the domestic broiler chick

    SciTech Connect

    Lee, S.R.

    1984-01-01

    Dietary levels of 0.6 to 0.8% magnesium in a corn-soy basal were rachitogenic. These rickets appeared most like phosphorus deficiency. Bone Ca/P ratios were numerically quite low implying a lack of transformation from amorphous calcium phosphate to hydroxyapatite. Bone alkaline phosphatase activity was elevated. Additional dietary phosphorus ameliorated, but could not overcome the rachitogenic effects of magnesium. Tibial dyschondroplasia (TD), induced by elevated dietary P, was decreased by high levels of dietary Mg, but with no decrease in plasma phosphorus. Anticoccidial ionophores fed in conjunction with a moderate dietary challenge of Mg (0.48%) produced no clear changes in plasma calcium or Mg, but did interact to reduce body weight. The diarrhea caused by magnesium intoxication is not due to hyperosmotic loads of Mg per se. Rather, Cl was observed to be the major ionic constituent of the gut osmotic load implying different gut ionic fluxes in control versus magnesium intoxicated chicks. These data imply that the cathartic action of Mg is due to hypersecretion of the gut. Effects mediated or modified by the CNS changed in magnesium intoxicated chicks. Such chicks appeared cold and stayed near the heat. When startled, they exhibited extreme avoidance behavior and seizures similar to epilepsy and/or Cl deficiency. Brain tissue Mg content did not concomitantly increase. Whether these effects are due to central signals is unclear.

  10. Illuminating the deleterious effects of light at night

    PubMed Central

    Nelson, Randy J.

    2011-01-01

    Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20th century, humans became exposed to bright and unnatural light at night for the first time in their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just “daytime” activities now run throughout the night; in many ways Western society now functions on a 24-hour schedule. Recent research suggests that this gain in freedom to function throughout the night may also come with significant repercussions. Disruption of our naturally evolved light and dark cycles can result in a wide range of physiological and behavioral changes with potentially serious medical implications. In this article we will discuss several mechanisms through which light at night may exert its effects on cancer, mood, and obesity, as well as potential ways to ameliorate the impact of light at night. PMID:21941596

  11. Blood cardioplegia delivery. Deleterious effects of potassium versus lidocaine.

    PubMed Central

    Leicher, F G; Magrassi, P; LaRaia, P J; Derkac, W M; Buckley, M J; Austen, W G

    1983-01-01

    Delivery of cardioplegic (CP) solutions to all regions of the myocardium is critical for optimal myocardial protection during cardiac surgery. However, there are little data regarding the effects of CP agents upon coronary vascular resistance (CVR) and CP delivery. Accordingly, we evaluated blood CP (Hct 30) delivery and CVR during 75 minutes of multi-dose hypothermic blood CP arrest in an in vivo isolated dog heart preparation. Three groups of dogs were studied: K(K+ = 30 mEq/L; n = 6), L (Lidocaine = 400 mg/L; K+ = 4 mEq/L; n = 6), and KL (K+ = 30 mEq/L, Lidocaine 400 mg/L; n = 6) during total cardiopulmonary bypass and moderate systemic hypothermia (28 C). Basal CVR was calculated by measuring total coronary flow (HR 120/min; mean aortic pressure = 80 mmHg) in the empty beating heart. After aortic cross-clamping, the blood CP solution was infused into the aortic root at a constant pressure (80 mmHg) and constant temperature (16 +/- 2 C) for 60 seconds at 15 minute intervals for a total arrest time of 75 min. Total CP flow, CVR, O2 consumption, lactate extraction/production, and K+ balance during 75 minutes of arrest and 30 minutes of reperfusion were determined. The distribution of the CP solution in the left ventricle was measured with radioactive microspheres (9 +/- 1 mu). Biopsy specimens were taken to measure wet to dry ratios. Values are mean +/- SEM. Data were analyzed by BMDP-P2V. During the first CP infusion, after aortic cross-clamping, no differences in CVR or CP distribution were found among the three groups. However, CVR was increased significantly in the K group during the second CP infusion (O': 0.98 +/- 0.20 mmHg/ml/min/100 g; 15': 2.66 +/- 0.82; p less than 0.001). The CVR remained high for the remainder of the arrest period. Moreover, total, epi- and endocardial flow decreased significantly (54%, p less than 0.001). In groups L and KL, no significant changes in CVR were seen. Groups K and KL showed a significant K+ extraction during the first CP infusion. During the early reperfusion period, K+ washout occurred in these two groups, which was not seen in the L group. There was no significant difference between the three groups in myocardial O2 consumption, lactate metabolism, and water content during the arrest and the reperfusion period. In conclusion, high concentrations of K+ (30 mEq/L) can markedly increase CVR and impair blood CP delivery and distribution. These effects can be prevented by lidocaine. These findings warrant reassessment of the various additives to CP solutions and their effects on CVR and CP distribution during multi-dose hypothermic CP arrest. PMID:6615050

  12. Deleterious effects of nonthermal electrons in shock ignition concept.

    PubMed

    Nicolaï, Ph; Feugeas, J-L; Touati, M; Ribeyre, X; Gus'kov, S; Tikhonchuk, V

    2014-03-01

    Shock ignition concept is a promising approach to inertial confinement fusion that may allow obtaining high fusion energy gains with the existing laser technology. However, the spike driving laser intensities in the range of 1-10 PW/cm2 produces the energetic electrons that may have a significant effect on the target performance. The hybrid numerical simulations including a radiation hydrodynamic code coupled to a rapid Fokker-Planck module are used to asses the role of hot electrons in the shock generation and the target preheat in the time scale of 100 ps and spatial scale of 100 μm. It is shown that depending on the electron energy distribution and the target density profile the hot electrons can either increase the shock amplitude or preheat the imploding shell. In particular, the exponential electron energy spectrum corresponding to the temperature of 30 keV in the present HiPER target design preheats the deuterium-tritium shell and jeopardizes its compression. Ways of improving the target performance are suggested. PMID:24730956

  13. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    PubMed Central

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  14. Beta-catenin in schizophrenia: Possibly deleterious novel mutation.

    PubMed

    Levchenko, Anastasia; Davtian, Stepan; Freylichman, Olga; Zagrivnaya, Maria; Kostareva, Anna; Malashichev, Yegor

    2015-08-30

    Schizophrenia is a debilitating psychiatric disorder, affecting approximately 1% of the human population. Mostly genetic factors contribute to schizophrenia, but the genetics are complex and various aspects of brain functioning and structure, from development to synapse plasticity, seem to be involved in the pathogenesis. The goal of the study was to look for novel mutations in genes, implicated in molecular networks, important in schizophrenia. In the study four candidate genes taking part in the WNT signaling pathway were analyzed by sequencing in a cohort of 87 schizophrenia patients from Saint Petersburg, Russia. The gene list included CTNNB1 (beta-catenin), GSK3B, WNT2B and WNT7B. The impact of discovered variants on the protein function was analyzed in silico. We found three variants in the genes CTNNB1 and WNT7B, absent in healthy controls, including 212 controls from the same geographic area. The novel mutation c.1943A>G (p.N648S) in CTNNB1 seems to be the best candidate for disease-associated mutation in this study, as it damages the protein product in silico. This is the first study reporting mutations in CTNNB1 in schizophrenia.

  15. [Deleterious effects of smoking on the musculoskeletal system].

    PubMed

    Duthon, V B; Ozturk, M; El-Achachi, S; Menetrey, J

    2014-07-16

    Tobacco smoking has important negative effects on the musculoskeletal system: decrease of bone mineral density, increase of the risk of injury, illness, and perioperative complications such as fracture-healing complications and wound complications. Orthopaedic surgeons should inform all patients of the increased risks associated with active smoking in the perioperative period and should encourage them to quit smoking four to eight weeks in advance of the proposed procedure. PMID:25141568

  16. Bombardment of the Hadean Earth: wholesome or deleterious?

    PubMed

    Ryder, Graham

    2003-01-01

    Graham Ryder died in January 2002 at the age of 53. He was a Staff Scientist at the Lunar and Planetary Science Institute in Houston, TX for most of his professional life, studying lunar petrology and planetary impacts. For many years he was the senior editor of the Proceedings of the Lunar and Planetary Science Conference, and he was the senior editor of Geological Society of America Special Paper 307, The Cretaceous-Tertiary Event and Other Catastrophes in Earth History. He was the major advocate for the 3.8 Ga lunar impact cataclysm and was just beginning to publish on correlations of the early lunar impact record to that of the other inner planets at the time of his death. Graham's abstract to the Rubey Colloquium was never presented. Although Graham made many of the points in this abstract to lunar science audiences, he certainly would have wanted these views to be shared with the Astrobiology community. We have taken the liberty of publishing this abstract with the Rubey proceedings, with only a few minor revisions to include reference to some recently published papers. These revisions were recommended by Gary R. Byerly, who reviewed this abstract for publication.

  17. Deleterious effects of bretylium on hemodynamic recovery from ventricular fibrillation.

    PubMed

    Euler, D E; Zeman, T W; Wallock, M E; Scanlon, P J

    1986-07-01

    To study the effects of bretylium on the restoration of circulatory function after resuscitation from ventricular fibrillation, closed-chest anesthetized dogs were electrically fibrillated for 1 minute followed by defibrillation (direct-current shock). After one control episode of fibrillation and defibrillation, 16 dogs received a bolus of bretylium (10 mg/kg intravenously). A second episode of fibrillation and defibrillation was induced in eight dogs 3 minutes after bretylium and in eight dogs 4 hours after bretylium. Prior to bretylium, mean arterial blood pressure spontaneously recovered to exceed 200 mm Hg by 2 minutes after defibrillation in all 16 dogs. However, after bretylium, 13 of 16 dogs were in electromechanical dissociation 2 minutes after defibrillation (p less than 0.001). Despite external chest compression, epinephrine, and sodium bicarbonate, a stable blood pressure could not be restored in 6 of 16 dogs. Clofilium, a bretylium analogue lacking sympathetic influences, did not alter the pattern of hemodynamic recovery following defibrillation in five of five dogs. The results suggest that the effects of bretylium on the sympathetic nervous system may profoundly influence the outcome of cardiac resuscitation from fibrillation. PMID:3728284

  18. Safer Aviation Materials Tested

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    2001-01-01

    A series of thermally stable polymer samples were tested. These materials are called low heat release materials and are designed for aircraft interior decorative materials. The materials are designed to give off a minimum amount of noxious gases when heated, which increases the possibility that people can escape from a burning aircraft. New cabin materials have suitably low heat release so that fire does not spread, toxic chemicals are not given off, and the fire-emergency escape time for crew and passengers is lengthened. These low heat-release materials have a variety of advantages and applications: interiors for ground-based facilities, interiors of space vehicles, and many commercial fire-protection environments. A microscale combustion calorimeter at the Federal Aviation Administration's (FAA) Technical Center tested NASA Langley Research Center materials samples. The calorimeter is shown. A sharp, quantitative, and reproducible heat-release-rate peak is obtained in the microscale heat-release-rate test. The newly tested NASA materials significantly reduced the heat release capacity and total heat release. The thermal stability and flammability behavior of the samples was very good. The new materials demonstrated a factor of 4 reduction in total heat release over ULTEM (a currently used material). This information is provided in the following barchart. In other tests, the materials showed greater than a factor 9 reduction in heat-release capacity over ULTEM. The newly tested materials were developed for low dielectric constant, low color, and good solubility. A scale up of the material samples is needed to determine the repeatability of the performance in larger samples. Larger panels composed of the best candidate materials will be tested in a larger scale FAA Technical Center fire facility. The NASA Glenn Research Center, Langley (Jeff Hinkley), and the FAA Technical Center (Richard Lyon) cooperatively tested these materials for the Accident Mitigation

  19. Thermal Protection Materials Development

    NASA Technical Reports Server (NTRS)

    Selvaduray, Guna; Cox, Michael

    1998-01-01

    The main portion of this contract year was spent on the development of materials for high temperature applications. In particular, thermal protection materials were constantly tested and evaluated for thermal shock resistance, high-temperature dimensional stability, and tolerance to hostile environmental effects. The analytical laboratory at the Thermal Protection Materials Branch (TPMB), NASA-Ames played an integral part in the process of materials development of high temperature aerospace applications. The materials development focused mainly on the determination of physical and chemical characteristics of specimens from the various research programs.

  20. Tailored Porous Materials

    SciTech Connect

    BARTON,THOMAS J.; BULL,LUCY M.; KLEMPERER,WALTER G.; LOY,DOUGLAS A.; MCENANEY,BRIAN; MISONO,MAKOTO; MONSON,PETER A.; PEZ,GUIDO; SCHERER,GEORGE W.; VARTULI,JAMES C.; YAGHI,OMAR M.

    1999-11-09

    Tailoring of porous materials involves not only chemical synthetic techniques for tailoring microscopic properties such as pore size, pore shape, pore connectivity, and pore surface reactivity, but also materials processing techniques for tailoring the meso- and the macroscopic properties of bulk materials in the form of fibers, thin films and monoliths. These issues are addressed in the context of five specific classes of porous materials: oxide molecular sieves, porous coordination solids, porous carbons, sol-gel derived oxides, and porous heteropolyanion salts. Reviews of these specific areas are preceded by a presentation of background material and review of current theoretical approaches to adsorption phenomena. A concluding section outlines current research needs and opportunities.

  1. Dealloying and Dealloyed Materials

    NASA Astrophysics Data System (ADS)

    McCue, Ian; Benn, Ellen; Gaskey, Bernard; Erlebacher, Jonah

    2016-07-01

    A successful working model for nanoporosity evolution during dealloying was introduced 15 years ago. Since that time, the field has rapidly expanded, with research groups from across the world studying dealloying and dealloyed materials. Dealloying has grown into a rich field, with some groups focusing on fundamentals and mechanisms of dealloying, other groups creating new porous metals and alloys, and even more groups studying their properties. Dealloying was originally considered only in the context of corrosion, but now it is considered a facile self-organization technique to fabricate high-surface-area, bicontinuous nanoporous materials. Owing to their high interfacial area and the versatility of metallic materials, nanoporous metals have found application in catalysis, sensing, actuation, electrolytic and ultracapacitor materials, high-temperature templates/scaffolds, battery anodes, and radiation damage-tolerant materials. In this review, we discuss the fundamental materials principles underlying the formation of dealloyed materials and then look at two major applications: catalysis and nanomechanics.

  2. Materials processing in space

    NASA Technical Reports Server (NTRS)

    Waldron, R. D.; Criswell, D. R.

    1982-01-01

    Processing-refining of raw materials from extraterrestrial sources is detailed for a space materials handling facility. The discussion is constrained to those steps necessary to separate desired components from raw or altered input ores, semi-purified feedstocks, or process scrap and convert the material into elements, alloys, and consumables. The materials are regarded as originating from dead satellites and boosters, lunar materials, and asteroids. Strong attention will be given to recycling reagent substances to avoid the necessity of transporting replacements. It is assumed that since no aqueous processes exist on the moon, the distribution of minerals will be homogeneous. The processing-refining scenario will include hydrochemical, pyrochemical, electrochemical, and physical techniques selected for the output mass rate/unit plant mass ratio. Flow charts of the various materials processing operations which could be performed with lunar materials are provided, noting the necessity of delivering several alloying elements from the earth due to scarcities on the moon.

  3. Dealloying and Dealloyed Materials

    NASA Astrophysics Data System (ADS)

    McCue, Ian; Benn, Ellen; Gaskey, Bernard; Erlebacher, Jonah

    2016-07-01

    A successful working model for nanoporosity evolution during dealloying was introduced 15 years ago. Since that time, the field has rapidly expanded, with research groups from across the world studying dealloying and dealloyed materials. Dealloying has grown into a rich field, with some groups focusing on fundamentals and mechanisms of dealloying, other groups creating new porous metals and alloys, and even more groups studying their properties. Dealloying was originally considered only in the context of corrosion, but now it is considered a facile self-organization technique to fabricate high-surface-area, bicontinuous nanoporous materials. Owing to their high interfacial area and the versatility of metallic materials, nanoporous metals have found application in catalysis, sensing, actuation, electrolytic and ultracapacitor materials, high-temperature templates/scaffolds, battery anodes, and radiation damage–tolerant materials. In this review, we discuss the fundamental materials principles underlying the formation of dealloyed materials and then look at two major applications: catalysis and nanomechanics.

  4. Materials and structures

    NASA Technical Reports Server (NTRS)

    Saito, Theodore T.; Langenbeck, Sharon L.; Al-Jamily, Ghanim; Arnold, Joe; Barbee, Troy; Coulter, Dan; Dolgin, Ben; Fichter, Buck; George, Patricia; Gorenstein, Paul

    1992-01-01

    Materials and structures technology covers a wide range of technical areas. Some of the most pertinent issues for the Astrotech 21 missions include dimensionally stable structural materials, advanced composites, dielectric coatings, optical metallic coatings for low scattered light applications, low scattered light surfaces, deployable and inflatable structures (including optical), support structures in 0-g and 1-g environments, cryogenic optics, optical blacks, contamination hardened surfaces, radiation hardened glasses and crystals, mono-metallic telescopes and instruments, and materials characterization. Some specific examples include low coefficients of thermal expansion (CTE) structures (0.01 ppm/K), lightweight thermally stable mirror materials, thermally stable optical assemblies, high reliability/accuracy (1 micron) deployable structures, and characterization of nanometer level behavior of materials/structures for interferometry concepts. Large filled-aperture concepts will require materials with CTE's of 10(exp 9) at 80 K, anti-contamination coatings, deployable and erectable structures, composite materials with CTE's less than 0.01 ppm/K and thermal hysteresis, 0.001 ppm/K. Gravitational detection systems such as LAGOS will require rigid/deployable structures, dimensionally stable components, lightweight materials with low conductivity, and high stability optics. The Materials and Structures panel addressed these issues and the relevance of the Astrotech 21 mission requirements by dividing materials and structures technology into five categories. These categories, the necessary development, and applicable mission/program development phasing are summarized. For each of these areas, technology assessments were made and development plans were defined.

  5. Materials research for fusion

    NASA Astrophysics Data System (ADS)

    Knaster, J.; Moeslang, A.; Muroga, T.

    2016-05-01

    Fusion materials research started in the early 1970s following the observation of the degradation of irradiated materials used in the first commercial fission reactors. The technological challenges of fusion energy are intimately linked with the availability of suitable materials capable of reliably withstanding the extremely severe operational conditions of fusion reactors. Although fission and fusion materials exhibit common features, fusion materials research is broader. The harder mono-energetic spectrum associated with the deuterium-tritium fusion neutrons (14.1 MeV compared to <2 MeV on average for fission neutrons) releases significant amounts of hydrogen and helium as transmutation products that might lead to a (at present undetermined) degradation of structural materials after a few years of operation. Overcoming the historical lack of a fusion-relevant neutron source for materials testing is an essential pending step in fusion roadmaps. Structural materials development, together with research on functional materials capable of sustaining unprecedented power densities during plasma operation in a fusion reactor, have been the subject of decades of worldwide research efforts underpinning the present maturity of the fusion materials research programme.

  6. Materials and structures

    NASA Astrophysics Data System (ADS)

    Saito, Theodore T.; Langenbeck, Sharon L.; Al-Jamily, Ghanim; Arnold, Joe; Barbee, Troy; Coulter, Dan; Dolgin, Ben; Fichter, Buck; George, Patricia; Gorenstein, Paul

    1992-08-01

    Materials and structures technology covers a wide range of technical areas. Some of the most pertinent issues for the Astrotech 21 missions include dimensionally stable structural materials, advanced composites, dielectric coatings, optical metallic coatings for low scattered light applications, low scattered light surfaces, deployable and inflatable structures (including optical), support structures in 0-g and 1-g environments, cryogenic optics, optical blacks, contamination hardened surfaces, radiation hardened glasses and crystals, mono-metallic telescopes and instruments, and materials characterization. Some specific examples include low coefficients of thermal expansion (CTE) structures (0.01 ppm/K), lightweight thermally stable mirror materials, thermally stable optical assemblies, high reliability/accuracy (1 micron) deployable structures, and characterization of nanometer level behavior of materials/structures for interferometry concepts. Large filled-aperture concepts will require materials with CTE's of 10(exp 9) at 80 K, anti-contamination coatings, deployable and erectable structures, composite materials with CTE's less than 0.01 ppm/K and thermal hysteresis, 0.001 ppm/K. Gravitational detection systems such as LAGOS will require rigid/deployable structures, dimensionally stable components, lightweight materials with low conductivity, and high stability optics. The Materials and Structures panel addressed these issues and the relevance of the Astrotech 21 mission requirements by dividing materials and structures technology into five categories. These categories, the necessary development, and applicable mission/program development phasing are summarized. For each of these areas, technology assessments were made and development plans were defined.

  7. Engineering Living Functional Materials

    PubMed Central

    2016-01-01

    Natural materials, such as bone, integrate living cells composed of organic molecules together with inorganic components. This enables combinations of functionalities, such as mechanical strength and the ability to regenerate and remodel, which are not present in existing synthetic materials. Taking a cue from nature, we propose that engineered ‘living functional materials’ and ‘living materials synthesis platforms’ that incorporate both living systems and inorganic components could transform the performance and the manufacturing of materials. As a proof-of-concept, we recently demonstrated that synthetic gene circuits in Escherichia coli enabled biofilms to be both a functional material in its own right and a materials-synthesis platform. To demonstrate the former, we engineered E. coli biofilms into a chemical-inducer-responsive electrical switch. To demonstrate the latter, we engineered E. coli biofilms to dynamically organize biotic-abiotic materials across multiple length scales, template gold nanorods, gold nanowires, and metal/semiconductor heterostructures, and synthesize semiconductor nanoparticles (Chen, A. Y. et al. (2014) Synthesis and patterning of tunable multiscale materials with engineered cells. Nat. Mater.13, 515–523.). Thus, tools from synthetic biology, such as those for artificial gene regulation, can be used to engineer the spatiotemporal characteristics of living systems and to interface living systems with inorganic materials. Such hybrids can possess novel properties enabled by living cells while retaining desirable functionalities of inorganic systems. These systems, as living functional materials and as living materials foundries, would provide a radically different paradigm of materials performance and synthesis–materials possessing multifunctional, self-healing, adaptable, and evolvable properties that are created and organized in a distributed, bottom-up, autonomously assembled, and environmentally sustainable manner. PMID

  8. Charge Photogeneration Experiments and Theory in Aggregated Squaraine Donor Materials for Improved Organic Solar Cell Efficiencies

    NASA Astrophysics Data System (ADS)

    Spencer, Susan Demetra

    Fossil fuel consumption has a deleterious effect on humans, the economy, and the environment. Renewable energy technologies must be identified and commercialized as quickly as possible so that the transition to renewables can happen at a minimum of financial and societal cost. Organic photovoltaic cells offer an inexpensive and disruptive energy technology, if the scientific challenges of understanding charge photogeneration in a bulk heterojunction material can be overcome. At RIT, there is a strong focus on creating new materials that can both offer fundamentally important scientific results relating to quantum photophysics, and simultaneously assist in the development of strong candidates for future commercialized technology. In this presentation, the results of intensive materials characterization of a series of squaraine small molecule donors will be presented, as well as a full study of the fabrication and optimization required to achieve >4% photovoltaic cell efficiency. A relationship between the molecular structure of the squaraine and its ability to form nanoscale aggregates will be explored. Squaraine aggregation will be described as a unique optoelectronic probe of the structure of the bulk heterojunction. This relationship will then be utilized to explain changes in crystallinity that impact the overall performance of the devices. Finally, a predictive summary will be given for the future of donor material research at RIT.

  9. Characterization of Nanophase Materials

    NASA Astrophysics Data System (ADS)

    Wang, Zhong Lin

    2000-01-01

    Engineering of nanophase materials and devices is of vital interest in electronics, semiconductors and optics, catalysis, ceramics and magnetism. Research associated with nanoparticles has widely spread and diffused into every field of scientific research, forming a trend of nanocrystal engineered materials. The unique properties of nanophase materials are entirely determined by their atomic scale structures, particularly the structures of interfaces and surfaces. Development of nanotechnology involves several steps, of which characterization of nanoparticles is indespensable to understand the behavior and properties of nanoparticles, aiming at implementing nanotechnolgy, controlling their behavior and designing new nanomaterials systems with super performance. The book will focus on structural and property characterization of nanocrystals and their assemblies, with an emphasis on basic physical approach, detailed techniques, data interpretation and applications. Intended readers of this comprehensive reference work are advanced graduate students and researchers in the field, who are specialized in materials chemistry, materials physics and materials science.

  10. Benzimidazole Based Aerogel Materials

    NASA Technical Reports Server (NTRS)

    Rhine, Wendell E. (Inventor); Mihalcik, David (Inventor)

    2016-01-01

    The present invention provides aerogel materials based on imidazoles and polyimidazoles. The polyimidazole based aerogel materials can be thermally stable up to 500 C or more, and can be carbonized to produce a carbon aerogel having a char yield of 60% or more, specifically 70% or more. The present invention also provides methods of producing polyimidazole based aerogel materials by reacting at least one monomer in a suitable solvent to form a polybenzimidazole gel precursor solution, casting the polybenzimidazole gel precursor solution into a fiber reinforcement phase, allowing the at least one gel precursor in the precursor solution to transition into a gel material, and drying the gel materials to remove at least a portion of the solvent, to obtain an polybenzimidazole-based aerogel material.

  11. Ultrasonic nondestructive materials characterization

    NASA Technical Reports Server (NTRS)

    Green, R. E., Jr.

    1986-01-01

    A brief review of ultrasonic wave propagation in solid materials is presented with consideration of the altered behavior in anisotropic and nonlinear elastic materials in comparison with isotropic and linear elastic materials. Some experimental results are described in which ultrasonic velocity and attenuation measurements give insight into materials microstructure and associated mechanical properties. Recent developments with laser beam non-contact generation and detection of ultrasound are presented. The results of several years of experimental measurements using high-power ultrasound are discussed, which provide substantial evidence of the inability of presently accepted theories to fully explain the interaction of ultrasound with solid materials. Finally, a special synchrotron X-ray topographic system is described which affords the possibility of observing direct interaction of ultrasonic waves with the microstructural features of real crystalline solid materials for the first time.

  12. NUCLEAR FUEL MATERIAL

    DOEpatents

    Goeddel, W.V.

    1962-06-26

    An improved method is given for making the carbides of nuclear fuel material. The metal of the fuel material, which may be a fissile and/or fertile material, is transformed into a silicide, after which the silicide is comminuted to the desired particle size. This silicide is then carburized at an elevated temperature, either above or below the melting point of the silicide, to produce an intimate mixture of the carbide of the fuel material and the carbide of silicon. This mixture of the fuel material carbide and the silicon carbide is relatively stable in the presence of moisture and does not exhibit the highly reactive surface condition which is observed with fuel material carbides made by most other known methods. (AEC)

  13. Femtosecond laser materials processing

    SciTech Connect

    Stuart, B. C., LLNL

    1998-06-02

    Femtosecond lasers enable materials processing of most any material with extremely high precision and negligible shock or thermal loading to the surrounding area Applications ranging from drilling teeth to cutting explosives to making high-aspect ratio cuts in metals with no heat-affected zone are made possible by this technology For material removal at reasonable rates, we developed a fully computer-controlled 15-Watt average power, 100-fs laser machining system.

  14. Feeder for particulate material

    SciTech Connect

    Christofer, D.E.; Stock, A.J.

    1981-03-24

    Feeder apparatus for feeding at a controlled variable rate particulate solid material, such as coal, from a supply conduit located above a gravimetric feeder to a discharge chute located below the feeder. The particulate material flows to the feeder from the supply conduit along a path having a generally vertical center line and the discharge chute provides a flow path having a generally vertical center line closely laterally spaced relative to the center line of flow to the feeder. The feeder apparatus has a horizontally extending housing with an upwardly facing inlet through which the material flows to the feeder and a downwardly facing outlet forming part of the discharge chute through which the material flows from the feeder. Within the housing is a main feeder conveyor including an endless belt with a generally horizontal span adapted to receive at one end the particulate material flowing to the feeder and to convey in a layer a measured quantity of material a horizontal distance across weighing means to an exit zone at the opposite end of the belt, the horizontal distance being substantially greater than the spacing between the center lines of flow to the feeder and through such discharge chute. Associated with the main feeder conveyor is a gravimetric control system for controlling the amount of material deposited on the belt. Particulate material that drops off the main conveyor belt at the exit zone is received on a return belt conveyor and carried in a reverse direction a sufficient distance to bring the material to the discharge chute. Cooperation between the main feeder conveyor and the return conveyor permits gravimetric feeding of particulate material to the discharge chute that is closely laterally spaced to the flow path of material to the main conveyor by a distance that is substantially less than the length of travel of the material on the main conveyor.

  15. Femtosecond laser materials processing

    SciTech Connect

    Stuart, B

    1998-08-05

    Femtosecond lasers enable materials processing of most any material with extremely high precision and negligible shock or thermal loading to the surrounding area. Applications ranging from drilling teeth to cutting explosives to precision cuts in composites are possible by using this technology. For material removal at reasonable rates, we have developed a fully computer-controlled 15-Watt average power, 100-fs laser machining system.

  16. Infrared fiber optic materials

    NASA Technical Reports Server (NTRS)

    Feigelson, Robert S.

    1987-01-01

    The development of IR fiber optics for use in astronomical and other space applications is summarized. Candidate materials were sought for use in the 1 to 200 micron and the 200 to 1000 micron wavelength range. Synthesis and optical characterization were carried out on several of these materials in bulk form. And the fabrication of a few materials in single crystal fiber optic form were studied.

  17. ANS materials databook

    SciTech Connect

    Marchbanks, M.F.

    1995-08-01

    Technical development in the Advanced Neutron Source (ANS) project is dynamic, and a continuously updated information source is necessary to provide readily usable materials data to the designer, analyst, and materials engineer. The Advanced Neutron Source Materials Databook (AMBK) is being developed as a part of the Advanced Neutron Source Materials Information System (AMIS). Its purpose is to provide urgently needed data on a quick-turnaround support basis for those design applications whose schedules demand immediate estimates of material properties. In addition to the need for quick materials information, there is a need for consistent application of data throughout the ANS Program, especially where only limited data exist. The AMBK is being developed to fill this need as well. It is the forerunner to the Advanced Neutron Source Materials Handbook (AMHB). The AMHB, as reviewed and approved by the ANS review process, will serve as a common authoritative source of materials data in support of the ANS Project. It will furnish documented evidence of the materials data used in the design and construction of the ANS system and will serve as a quality record during any review process whose objective is to establish the safety level of the ANS complex. The information in the AMBK and AMHB is also provided in electronic form in a dial-up computer database known as the ANS Materials Database (AMDB). A single consensus source of materials information prepared and used by all national program participants has several advantages. Overlapping requirements and data needs of various sub-projects and subcontractors can be met by a single document which is continuously revised. Preliminary and final safety analysis reports, stress analysis reports, equipment specifications, materials service reports, and many other project-related documents can be substantially reduced in size and scope by appropriate reference to a single data source.

  18. Multilayer Insulation Material Guidelines

    NASA Technical Reports Server (NTRS)

    Finckenor, M. M.; Dooling, D.

    1999-01-01

    Multilayer Insulation Material Guidelines provides data on multilayer insulation materials used by previous spacecraft such as Spacelab and the Long-Duration Exposure Facility and outlines other concerns. The data presented in the document are presented for information only. They can be used as guidelines for multilayer insulation design for future spacecraft provided the thermal requirements of each new design and the environmental effects on these materials are taken into account.

  19. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-05-15

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  20. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2010-07-13

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  1. Materials for Slack Diaphragms

    NASA Technical Reports Server (NTRS)

    Puschmann, Traute

    1940-01-01

    This report deals with systematic experiments carried out on five diaphragm materials with different pretreatment, for the purpose of ascertaining the suitability of such materials for slack diaphragms. The relationship of deflection and load, temperature and moisture, was recorded. Of the explored materials, synthetic leather, balloon cloth, goldbeaters skin, Igelit and Buna, synthetic leather treated with castor oil is the most suitable material for the small pressure range required. Balloon cloth is nearly as good, while goldbeaters skin, Igelit and Buna were found to be below the required standards.

  2. Assessment of biobased materials

    SciTech Connect

    Chum, H.L.

    1989-12-01

    Biobased materials are polymers derived from renewable resources by chemical or combined chemical and mechanical methods, or produced directly in biological processes. Combinations of renewable and conventional fossil-fuel-derived plastics are also biobased materials. This assessment reviews materials from renewable resources and their properties including major biopolymers produced by plants and selected animal sources. Examples discussed are wood, its polymeric components such as cellulose and lignin, related polymers such as chitin, other carbohydrate polymers such as starch, which when combined with plastics can impart environmental degradability to the resulting material. The conventional role of inexpensive wood flour as a filler is reviewed as well as the future research necessary to bring these materials into a higher value use as a reinforcing material for composites. Automotive, building, and packaging materials applications are considered. Bioproduction of materials is reviewed for selected polymers such as cellulose, other plant cell wall polymers, and proteins, with emphasis on silk and wool. These materials can be produced with specific properties such as biodegradability (e.g., polyhydroxybutyrate and valerate copolymers, polylactide polymers) or specific mechanical properties.

  3. Fluorinated elastomeric materials

    DOEpatents

    Lagow, Richard J.; Dumitru, Earl T.

    1990-02-13

    This invention relates to a method of making perfluorinated elastomeric materials, and to materials made by such methods. In the full synthetic scheme, a partially fluorinated polymeric compound, with moieties to prevent crystallization, is created. It is then crosslinked to a desired degree, then perfluorinated. Various intermediate materials, such as partially fluorinated crosslinked polymers, have useful properties, and are or may become commercially available. One embodiment of this invention therefore relates to perfluorination of a selected partially fluorinated, crosslinked material, which is one step of the full synthetic scheme.

  4. Fluorinated elastomeric materials

    DOEpatents

    Lagow, Richard J.; Dumitru, Earl T.

    1986-11-04

    This invention relates to a method of making perfluorinated elastomeric materials, and to materials made by such methods. In the full synthetic scheme, a partially fluorinated polymeric compound, with moieties to prevent crystallization, is created. It is then crosslinked to a desired degree, then perfluorinated. Various intermediate materials, such as partially fluorinated crosslinked polymers, have useful properties, and are or may become commercially available. One embodiment of this invention therefore relates to perfluorination of a selected partially fluorinated, crosslinked material, which is one step of the full synthetic scheme.

  5. Materials Science Laboratory

    NASA Technical Reports Server (NTRS)

    Jackson, Dionne

    2005-01-01

    The NASA Materials Science Laboratory (MSL) provides science and engineering services to NASA and Contractor customers at KSC, including those working for the Space Shuttle. International Space Station. and Launch Services Programs. These services include: (1) Independent/unbiased failure analysis (2) Support to Accident/Mishap Investigation Boards (3) Materials testing and evaluation (4) Materials and Processes (M&P) engineering consultation (5) Metrology (6) Chemical analysis (including ID of unknown materials) (7) Mechanical design and fabrication We provide unique solutions to unusual and urgent problems associated with aerospace flight hardware, ground support equipment and related facilities.

  6. Flexible Material Systems Testing

    NASA Technical Reports Server (NTRS)

    Lin, John K.; Shook, Lauren S.; Ware, Joanne S.; Welch, Joseph V.

    2010-01-01

    An experimental program has been undertaken to better characterize the stress-strain characteristics of flexible material systems to support a NASA ground test program for inflatable decelerator material technology. A goal of the current study is to investigate experimental methods for the characterization of coated woven material stiffness. This type of experimental mechanics data would eventually be used to define the material inputs of fluid-structure interaction simulation models. The test methodologies chosen for this stress-strain characterization are presented along with the experimental results.

  7. Mechanics of materials model

    NASA Technical Reports Server (NTRS)

    Meister, Jeffrey P.

    1987-01-01

    The Mechanics of Materials Model (MOMM) is a three-dimensional inelastic structural analysis code for use as an early design stage tool for hot section components. MOMM is a stiffness method finite element code that uses a network of beams to characterize component behavior. The MOMM contains three material models to account for inelastic material behavior. These include the simplified material model, which assumes a bilinear stress-strain response; the state-of-the-art model, which utilizes the classical elastic-plastic-creep strain decomposition; and Walker's viscoplastic model, which accounts for the interaction between creep and plasticity that occurs under cyclic loading conditions.

  8. The Materials Genome Project

    NASA Astrophysics Data System (ADS)

    Aourag, H.

    2008-09-01

    In the past, the search for new and improved materials was characterized mostly by the use of empirical, trial- and-error methods. This picture of materials science has been changing as the knowledge and understanding of fundamental processes governing a material's properties and performance (namely, composition, structure, history, and environment) have increased. In a number of cases, it is now possible to predict a material's properties before it has even been manufactured thus greatly reducing the time spent on testing and development. The objective of modern materials science is to tailor a material (starting with its chemical composition, constituent phases, and microstructure) in order to obtain a desired set of properties suitable for a given application. In the short term, the traditional "empirical" methods for developing new materials will be complemented to a greater degree by theoretical predictions. In some areas, computer simulation is already used by industry to weed out costly or improbable synthesis routes. Can novel materials with optimized properties be designed by computers? Advances in modelling methods at the atomic level coupled with rapid increases in computer capabilities over the last decade have led scientists to answer this question with a resounding "yes'. The ability to design new materials from quantum mechanical principles with computers is currently one of the fastest growing and most exciting areas of theoretical research in the world. The methods allow scientists to evaluate and prescreen new materials "in silico" (in vitro), rather than through time consuming experimentation. The Materials Genome Project is to pursue the theory of large scale modeling as well as powerful methods to construct new materials, with optimized properties. Indeed, it is the intimate synergy between our ability to predict accurately from quantum theory how atoms can be assembled to form new materials and our capacity to synthesize novel materials atom

  9. Thermoelectric materials having porosity

    SciTech Connect

    Heremans, Joseph P.; Jaworski, Christopher M.; Jovovic, Vladimir; Harris, Fred

    2014-08-05

    A thermoelectric material and a method of making a thermoelectric material are provided. In certain embodiments, the thermoelectric material comprises at least 10 volume percent porosity. In some embodiments, the thermoelectric material has a zT greater than about 1.2 at a temperature of about 375 K. In some embodiments, the thermoelectric material comprises a topological thermoelectric material. In some embodiments, the thermoelectric material comprises a general composition of (Bi.sub.1-xSb.sub.x).sub.u(Te.sub.1-ySe.sub.y).sub.w, wherein 0.ltoreq.x.ltoreq.1, 0.ltoreq.y.ltoreq.1, 1.8.ltoreq.u.ltoreq.2.2, 2.8.ltoreq.w.ltoreq.3.2. In further embodiments, the thermoelectric material includes a compound having at least one group IV element and at least one group VI element. In certain embodiments, the method includes providing a powder comprising a thermoelectric composition, pressing the powder, and sintering the powder to form the thermoelectric material.

  10. Material for radioactive protection

    DOEpatents

    Taylor, R.S.; Boyer, N.W.

    A boron containing burn resistant, low-level radiation protection material useful, for example, as a liner for radioactive waste disposal and storage, a component for neutron absorber, and a shield for a neutron source is described. The material is basically composed of borax in the range of 25 to 50%, coal tar in the range of 25 to 37.5%, with the remainder being an epoxy resin mix. A preferred composition is 50% borax, 25% coal tar and 25% epoxy resin. The material is not susceptible to burning and is about 1/5 the cost of existing radiation protection material utilized in similar applications.

  11. [Materials for construction sector].

    PubMed

    Macchia, C

    2012-01-01

    The construction sector is characterized by high complexity due to several factors. There are a lot of processes within the building sites and they need the use of different materials with the help of appropriate technologies. Traditional materials have evolved and diversified, meanwhile new products and materials appeared and still appear, offering services which meet user needs, but that often involve risks to the health of workers. Research in the field of materials, promoted and carried out at various levels, has led to interesting results, encoded in the form of rules and laws.

  12. LDEF materials overview

    NASA Technical Reports Server (NTRS)

    Stein, Bland A.

    1993-01-01

    The flight and retrieval of the National Aeronautics and Space Administration's Long Duration Exposure Facility (LDEF) provided an opportunity for the study of the low-Earth orbit (LEO) environment and long-duration space environmental effects (SEE) on materials that is unparalleled in the history of the U.S. Space Program. The 5-year, 9-month flight of LDEF greatly enhanced the potential value of all materials on LDEF to the international SEE community, compared to that of the original 1-year flight plan. The remarkable flight attitude stability of LDEF enables specific analyses of individual and combined effects of LEO environmental parameters on identical materials on the same space vehicle. NASA recognized this potential by forming the LDEF Space Environmental Effects on Materials Special Investigation Group (MSIG) to address the greatly expanded materials and LEO space environment analysis opportunities available in the LDEF structure, experiment trays, and corollary measurements so that the combined value of all LDEF materials data to current and future space missions will be addressed and documented. An overview of the interim LDEF materials findings of the principal investigators and the Materials Special Investigation Group is provided. These revelations are based on observations of LEO environmental effects on materials made in space during LDEF retrieval and during LDEF tray deintegration at the Kennedy Space Center, and on findings of approximately 1.5 years of laboratory analyses of LDEF materials by the LDEF materials scientists. These findings were extensively reviewed and discussed at the MSIG-sponsored LDEF Materials Workshop '91. The results are presented in a format that categorizes the revelations as 'clear findings' or 'obscure preliminary findings' (and progress toward their resolution), plus resultant needs for new space materials developments and ground simulation testing/analytical modeling, in seven categories: materials

  13. Biogenic Impact on Materials

    NASA Astrophysics Data System (ADS)

    Stephan, Ina; Askew, Peter D.; Gorbushina, Anna A.; Grinda, Manfred; Hertel, Horst; Krumbein, Wolfgang E.; Müller, Rolf-Joachim; Pantke, Michael; Plarre, Rüdiger (Rudy); Schmitt, Guenter; Schwibbert, Karin

    Materials as constituents of products or components of technical systems rarely exist in isolation and many must cope with exposure in the natural world. This chapter describes methods that simulate how a material is influenced through contact with living systems such as microorganisms and arthropods. Both unwanted and desirable interactions are considered. This biogenic impact on materials is intimately associated with the environment to which the material is exposed (Materials-Environment Interaction, Chap. 15). Factors such as moisture, temperature and availability of food sources all have a significant influence on biological systems. Corrosion (Chap. 12) and wear (Chap. 13) can also be induced or enhanced in the presence of microorganisms. Section 14.1 introduces the categories between desired (biodegradation) and undesired (biodeterioration) biological effects on materials. It also introduces the role of biocides for the protection of materials. Section 14.2 describes the testing of wood as a building material especially against microorganisms and insects. Section 14.3 characterizes the test methodologies for two other groups of organic materials, namely polymers (Sect. 14.3.1) and paper and textiles (Sect. 14.3.2). Section 14.4 deals with the susceptibility of inorganic materials such as metals (Sect. 14.4.1), concrete (Sect. 14.4.2) and ceramics (Sect. 14.4.3) to biogenic impact. Section 14.5 treats the testing methodology concerned with the performance of coatings and coating materials. In many of these tests specific strains of organisms are employed. It is vital that these strains retain their ability to utilize/attack the substrate from which they were isolated, even when kept for many years in the laboratory. Section 14.6 therefore considers the importance of maintaining robust and representative test organisms that are as capable of utilizing a substrate as their counterparts in nature such that realistic predictions of performance can be made.

  14. Nanoprobes, nanostructured materials and solid state materials

    NASA Astrophysics Data System (ADS)

    Yin, Houping

    2005-07-01

    Novel templates have been developed to prepare nanostructured porous materials through nonsurfactant templated pathway. And new applications of these materials, such as drug delivery and molecular imprinting, have been explored. The relationship between template content and pore structure has been investigated. The composition and pore structures were studied in detail using IR, TGA, SEM, TEM, BET and XRD. The obtained mesoporous materials have tunable diameters in the range of 2--12 nm. Due to the many advantages of this nonsurfactant templated pathway, such as environment friendly and biocompatibility, controlled release of antibiotics in the nanoporous materials were studied. The in vitro release properties were found to depend on the silica structures which were well tuned by varying the template content. A controlled long-term release pattern of vancomycin was achieved when the template content was 30 wt% or lower. Nanoscale electrochemical probes with dimensions as small as 50 nm in diameter and 1--2 mum in length were fabricated using electron beam deposition on the apex of conventional micron size electrodes. The electroactive region was limited to the extreme tip of the nanoprobe by coating with an insulating polymer and re-opening of the coating at the extreme tip. The novel nanoelectrodes thus prepared were employed to probe neurons in mouse brain slice and the results suggest that the nanoprobes were capable of recording neuronal excitatory postsynaptic potential signals. Interesting solid state chemistry was found in oxygenated iron phthalocyanine. Their Mossbauer spectra show the formation of four oxygenated species apart from the unoxygenated parent compound. The oxygen-bridged compounds formed in the solid matrix bear no resemblance to the one formed by solution chemistry. Tentative assignment of species has been made with the help of Mossbauer and IR spectroscopy. An effort to modify aniline trimer for potential nanoelectronics applications and to

  15. Packaging Materials Properties Data

    SciTech Connect

    Leduc, D.

    1991-10-30

    Several energy absorbing materials are used in nuclear weapons component shipping containers recently designed for the Y-12 Plant Program Management Packaging Group. As a part of the independent review procedure leading to Certificates of Compliance, the U.S. Department of Energy Technical Safety Review Panels requested compression versus deflection . data on these materials. This report is a compilation of that data.

  16. Packaging materials properties data

    SciTech Connect

    Walker, M.S.

    1991-01-01

    Several energy absorbing materials are used in nuclear weapons component shipping containers recently designed for the Y-12 Plant Program Management Packaging Group. As a part of the independent review procedure leading to Certificates of Compliance, the US Department of Energy Technical Safety Review Panels requested compression versus deflection data on these materials. This report is a compilation of that data.

  17. Hydrocarbonaceous material upgrading method

    SciTech Connect

    Brecher, Lee E.; Mones, Charles G.; Guffey, Frank D.

    2015-06-02

    A hydrocarbonaceous material upgrading method may involve a novel combination of heating, vaporizing and chemically reacting hydrocarbonaceous feedstock that is substantially unpumpable at pipeline conditions, and condensation of vapors yielded thereby, in order to upgrade that feedstock to a hydrocarbonaceous material condensate that meets crude oil pipeline specification.

  18. MULTISCALE PHENOMENA IN MATERIALS

    SciTech Connect

    A. BISHOP

    2000-09-01

    This project developed and supported a technology base in nonequilibrium phenomena underpinning fundamental issues in condensed matter and materials science, and applied this technology to selected problems. In this way the increasingly sophisticated synthesis and characterization available for classes of complex electronic and structural materials provided a testbed for nonlinear science, while nonlinear and nonequilibrium techniques helped advance our understanding of the scientific principles underlying the control of material microstructure, their evolution, fundamental to macroscopic functionalities. The project focused on overlapping areas of emerging thrusts and programs in the Los Alamos materials community for which nonlinear and nonequilibrium approaches will have decisive roles and where productive teamwork among elements of modeling, simulations, synthesis, characterization and applications could be anticipated--particularly multiscale and nonequilibrium phenomena, and complex matter in and between fields of soft, hard and biomimetic materials. Principal topics were: (i) Complex organic and inorganic electronic materials, including hard, soft and biomimetic materials, self-assembly processes and photophysics; (ii) Microstructure and evolution in multiscale and hierarchical materials, including dynamic fracture and friction, dislocation and large-scale deformation, metastability, and inhomogeneity; and (iii) Equilibrium and nonequilibrium phases and phase transformations, emphasizing competing interactions, frustration, landscapes, glassy and stochastic dynamics, and energy focusing.

  19. MATERIAL TRACKING USING LANMAS

    SciTech Connect

    Armstrong, F.

    2010-06-07

    LANMAS is a transaction-based nuclear material accountability software product developed to replace outdated and legacy accountability systems throughout the DOE. The core underlying purpose of LANMAS is to track nuclear materials inventory and report transactions (movement, mixing, splitting, decay, etc.) to the Nuclear Materials Management and Safeguards System (NMMSS). While LANMAS performs those functions well, there are many additional functions provided by the software product. As a material is received onto a site or created at a site, its entire lifecycle can be tracked in LANMAS complete to its termination of safeguards. There are separate functions to track material movements between and within material balance areas (MBAs). The level of detail for movements within a MBA is configurable by each site and can be as high as a site designation or as detailed as building/room/rack/row/position. Functionality exists to track the processing of materials, either as individual items or by modeling a bulk process as an individual item to track inputs and outputs from the process. In cases where sites have specialized needs, the system is designed to be flexible so that site specific functionality can be integrated into the product. This paper will demonstrate how the software can be used to input material into an account and track it to its termination of safeguards.

  20. Canadian Materials 1972.

    ERIC Educational Resources Information Center

    Wintrob, Ralph, Ed.

    A variety of media is encompassed in this annotated awareness list of Canadian produced or Canadian oriented materials. Its purpose is to include all materials published or reprinted in 1972 which are suitable for use in school resource centers from kindergarten to twelfth grade. Main entries are arranged alphabetically by title with some subject…

  1. Packaging Your Training Materials

    ERIC Educational Resources Information Center

    Espeland, Pamela

    1977-01-01

    The types of packaging and packaging materials to use for training materials should be determined during the planning of the training programs, according to the packaging market. Five steps to follow in shopping for packaging are presented, along with a list of packaging manufacturers. (MF)

  2. Airframe materials for HSR

    NASA Technical Reports Server (NTRS)

    Bales, Thomas T.

    1992-01-01

    Vugraphs are presented to show the use of refractory materials for the skin of the High speed Civil Transport (HSCT). Examples are given of skin temperature ranges, failure mode weight distribution, tensile properties as a function of temperature, and components to be constructed from composite materials. The responsibilities of various aircraft companies for specific aircraft components are defined.

  3. NBS: Materials measurements

    NASA Technical Reports Server (NTRS)

    Manning, J. R.

    1981-01-01

    Measurement of materials properties and thermophysical properties is described. The topics discussed are: surface tensions and their variations with temperature and impurities; convection during unidirectional solidification: measurement of high temperature thermophysical properties of tungsten liquid and solid; thermodynamic properties of refractory materials at high temperatures; and experimental and theoretical studies in wetting and multilayer adsorption.

  4. Marine Education Materials System.

    ERIC Educational Resources Information Center

    Gammisch, Sue; Gray, Kevin

    1980-01-01

    Described is a marine education materials clearinghouse, the Marine Education Materials System (MEMS). MEMS classifies marine education documents and reproduces them on microfiche for distribution. There are 25 distribution centers, each of which has a collection of documents and provides assistance on a request basis to teachers. (Author/DS)

  5. Sex Education Materials.

    ERIC Educational Resources Information Center

    Singer-Magdoff, Laura

    1969-01-01

    After briefly discussing the philosophy of sex education and appraising generally the nature of the instructional methods and materials currently in use in the schools, the author provides brief but incisive reviews of a number of films, filmstrips, and other instructional materials dealing with sex. The reviews are continued in the succeeding…

  6. Nanocrystalline heterojunction materials

    SciTech Connect

    Elder, Scott H.; Su, Yali; Gao, Yufei; Heald, Steve M.

    2003-07-15

    Mesoporous nanocrystalline titanium dioxide heterojunction materials are disclosed. In one disclosed embodiment, materials comprising a core of titanium dioxide and a shell of a molybdenum oxide exhibit a decrease in their photoadsorption energy as the size of the titanium dioxide core decreases.

  7. Nanocrystalline Heterojunction Materials

    SciTech Connect

    Elder, Scott H.; Su, Yali; Gao, Yufei; Heald, Steve M.

    2004-02-03

    Mesoporous nanocrystalline titanium dioxide heterojunction materials and methods of making the same are disclosed. In one disclosed embodiment, materials comprising a core of titanium dioxide and a shell of a molybdenum oxide exhibit a decrease in their photoadsorption energy as the size of the titanium dioxide core decreases.

  8. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Loewy, R. G.; Wiberley, S. E.

    1985-01-01

    Various topics relating to composite structural materials for use in aircraft structures are discussed. The mechanical properties of high performance carbon fibers, carbon fiber-epoxy interface bonds, composite fractures, residual stress in high modulus and high strength carbon fibers, fatigue in composite materials, and the mechanical properties of polymeric matrix composite laminates are among the topics discussed.

  9. Environmental materials and interfaces

    SciTech Connect

    Not Available

    1991-11-01

    A workshop that explored materials and interfaces research needs relevant to national environmental concerns was conducted at Pacific Northwest Laboratory. The purposes of the workshop were to refine the scientific research directions being planned for the Materials and Interface Program in the Molecular Science Research Center (MSRC) and further define the research and user equipment to the included as part of the proposed Environmental and Molecular Science Laboratory (EMSL). Three plenary information sessions served to outline the background, objectives, and status of the MSRC and EMSL initiatives; selected specific areas with environmentally related materials; and the status of capabilities and facilities planned for the EMSL. Attention was directed to four areas where materials and interface science can have a significant impact on prevention and remediation of environmental problems: in situ detection and characterization of hazardous wastes (sensors), minimization of hazardous waste (separation membranes, ion exchange materials, catalysts), waste containment (encapsulation and barrier materials), and fundamental understanding of contaminant transport mechanisms. During all other sessions, the participants were divided into three working groups for detailed discussion and the preparation of a written report. The working groups focused on the areas of interface structure and chemistry, materials and interface stability, and materials synthesis. These recommendations and suggestions for needed research will be useful for other researchers in proposing projects and for suggesting collaborative work with MSRC researchers. 1 fig.

  10. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Ansell, G. S.; Wiberley, S. E.

    1978-01-01

    The purpose of the RPI composites program is to develop advanced technology in the areas of physical properties, structural concepts and analysis, manufacturing, reliability and life prediction. Concommitant goals are to educate engineers to design and use composite materials as normal or conventional materials. A multifaceted program was instituted to achieve these objectives.

  11. Materials inventory management manual

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This NASA Materials Inventory Management Manual (NHB 4100.1) is issued pursuant to Section 203(c)(1) of the National Aeronautics and Space Act of 1958 (42 USC 2473). It sets forth policy, performance standards, and procedures governing the acquisition, management and use of materials. This Manual is effective upon receipt.

  12. Materials Science and Engineering

    SciTech Connect

    Lesuer, D.R.

    1993-03-01

    Five papers are included: processing/characterization of laminated metal composites, casting process modeling, characterizing the failure of composite materials, fiber-optic Raman spectroscopy for cure monitoring of advanced polymer composites, and modeling superplastic materials. The papers are processed separately for the data base.

  13. Gravitation in Material Media

    ERIC Educational Resources Information Center

    Ridgely, Charles T.

    2011-01-01

    When two gravitating bodies reside in a material medium, Newton's law of universal gravitation must be modified to account for the presence of the medium. A modified expression of Newton's law is known in the literature, but lacks a clear connection with existing gravitational theory. Newton's law in the presence of a homogeneous material medium…

  14. Detecting Illicit Nuclear Materials

    SciTech Connect

    Kouzes, Richard T.

    2005-09-01

    The threat that weapons of mass destruction might enter the United States has led to a number of efforts for the detection and interdiction of nuclear, radiological, chemical, and biological weapons at our borders. There have been multiple deployments of instrumentation to detect radiation signatures to interdict radiological material, including weapons and weapons material worldwide.

  15. Thermal Protection Materials

    NASA Technical Reports Server (NTRS)

    Johnson, Sylvia M.

    2011-01-01

    Thermal protection materials and systems (TPS) are required to protect a vehicle returning from space or entering an atmosphere. The selection of the material depends on the heat flux, heat load, pressure, and shear and other mechanical loads imposed on the material, which are in turn determined by the vehicle configuration and size, location on the vehicle, speed, a trajectory, and the atmosphere. In all cases the goal is to use a material that is both reliable and efficient for the application. Reliable materials are well understood and have sufficient test data under the appropriate conditions to provide confidence in their performance. Efficiency relates to the behavior of a material under the specific conditions that it encounters TPS that performs very well at high heat fluxes may not be efficient at lower heat fluxes. Mass of the TPS is a critical element of efficiency. This talk will review the major classes of TPS, reusable or insulating materials and ablators. Ultra high temperature ceramics for sharp leading edges will also be reviewed. The talk will focus on the properties and behavior of these materials.

  16. Impacted material placement plans

    SciTech Connect

    Hickey, M.J.

    1997-01-29

    Impacted material placement plans (IMPP) are documents identifying the essential elements in placing remediation wastes into disposal facilities. Remediation wastes or impacted material(s) are those components used in the construction of the disposal facility exclusive of the liners and caps. The components might include soils, concrete, rubble, debris, and other regulatory approved materials. The IMPP provides the details necessary for interested parties to understand the management and construction practices at the disposal facility. The IMPP should identify the regulatory requirements from applicable DOE Orders, the ROD(s) (where a part of a CERCLA remedy), closure plans, or any other relevant agreements or regulations. Also, how the impacted material will be tracked should be described. Finally, detailed descriptions of what will be placed and how it will be placed should be included. The placement of impacted material into approved on-site disposal facilities (OSDF) is an integral part of gaining regulatory approval. To obtain this approval, a detailed plan (Impacted Material Placement Plan [IMPP]) was developed for the Fernald OSDF. The IMPP provides detailed information for the DOE, site generators, the stakeholders, regulatory community, and the construction subcontractor placing various types of impacted material within the disposal facility.

  17. 76 FR 35918 - Nixon Presidential Historical Materials; Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials; Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of Opening of Additional Materials. SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  18. 77 FR 58179 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration ACTION: Notice of opening of additional materials SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  19. 75 FR 68384 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of Opening of Additional Materials. SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  20. 77 FR 31400 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of Opening of Additional Materials. SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  1. 76 FR 62856 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of opening of additional materials. SUMMARY: This notice announces the opening of Nixon Presidential Historical Materials by the Richard Nixon...

  2. 75 FR 30863 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of opening of additional materials. SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  3. 76 FR 27092 - Nixon Presidential Historical Materials: Opening of Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... RECORDS ADMINISTRATION Nixon Presidential Historical Materials: Opening of Materials AGENCY: National Archives and Records Administration. ACTION: Notice of opening of additional materials. SUMMARY: This notice announces the opening of additional Nixon Presidential Historical Materials by the Richard...

  4. Mitigating the Effects of the Space Radiation Environment: A Novel Approach of Using Graded-Z Materials

    NASA Technical Reports Server (NTRS)

    Atwell, William; Rojdev, Kristina; Aghara, Sukesh; Sriprisan, Sirikul

    2013-01-01

    In this paper we present a novel space radiation shielding approach using various material lay-ups, called "Graded-Z" shielding, which could optimize cost, weight, and safety while mitigating the radiation exposures from the trapped radiation and solar proton environments, as well as the galactic cosmic radiation (GCR) environment, to humans and electronics. In addition, a validation and verification (V&V) was performed using two different high energy particle transport/dose codes (MCNPX & HZETRN). Inherently, we know that materials having high-hydrogen content are very good space radiation shielding materials. Graded-Z material lay-ups are very good trapped electron mitigators for medium earth orbit (MEO) and geostationary earth orbit (GEO). In addition, secondary particles, namely neutrons, are produced as the primary particles penetrate a spacecraft, which can have deleterious effects to both humans and electronics. The use of "dopants," such as beryllium, boron, and lithium, impregnated in other shielding materials provides a means of absorbing the secondary neutrons. Several examples of optimized Graded-Z shielding layups that include the use of composite materials are presented and discussed in detail. This parametric shielding study is an extension of some earlier pioneering work we (William Atwell and Kristina Rojdev) performed in 20041 and 20092.

  5. Fingerprinting of Materials

    NASA Technical Reports Server (NTRS)

    Workman, Gary L

    1992-01-01

    Recent issues emerging in our fiscal and ecological environments have promulgated that federal agencies shall promote activities which respond to the improvement of both. In response to these developments, the National Aeronautics and Space Administration (NASA) has undertaken an innovative approach to improve the control of materials used in all NASA manufacturing activities. In concert with this goal, NASA is requiring that its contractors and their sub-contractors perform a more intensive consolidation of technologies that can provide an accounting of materials, which includes in-coming materials, materials in process, end-products and waste materials. The purpose of this handbook is to provide guidelines to NASA and its contractor personnel for the planning and implementation of chemical fingerprinting programs and to illustrate the chemical and statistical fundamentals needed for successful use of chemical fingerprinting.

  6. Materials Integrating Photochemical Upconversion.

    PubMed

    McCusker, Catherine E; Castellano, Felix N

    2016-04-01

    This review features recent experimental work focused on the preparation and characterization of materials that integrate photochemical upconversion derived from sensitized triplet-triplet annihilation, resulting in the conversion of low energy photons to higher energy light, thereby enabling numerous wavelength-shifting applications. Recent topical developments in upconversion include encapsulating or rigidifying fluid solutions to give them mechanical strength, adapting inert host materials to enable upconversion, and using photoactive materials that incorporate the sensitizer and/or the acceptor. The driving force behind translating photochemical upconversion from solution into hard and soft materials is the incorporation of upconversion into devices and other applications. At present, some of the most promising applications of upconversion materials include imaging and fluorescence microscopy, photoelectrochemical devices, water disinfection, and solar cell enhancement.

  7. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  8. Extraterrestrial materials processing

    NASA Technical Reports Server (NTRS)

    Steurer, W. H.

    1982-01-01

    The first year results of a multi-year study of processing extraterrestrial materials for use in space are summarized. Theoretically, there are potential major advantages to be derived from the use of such materials for future space endeavors. The types of known or postulated starting raw materials are described including silicate-rich mixed oxides on the Moon, some asteroids and Mars; free metals in some asteroids and in small quantities in the lunar soil; and probably volatiles like water and CO2 on Mars and some asteroids. Candidate processes for space materials are likely to be significantly different from their terrestrial counterparts largely because of: absence of atmosphere; lack of of readily available working fluids; low- or micro-gravity; no carbon-based fuels; readily available solar energy; and severe constraints on manned intervention. The extraction of metals and oxygen from lunar material by magma electrolysis or by vapor/ion phase separation appears practical.

  9. Materials Integrating Photochemical Upconversion.

    PubMed

    McCusker, Catherine E; Castellano, Felix N

    2016-04-01

    This review features recent experimental work focused on the preparation and characterization of materials that integrate photochemical upconversion derived from sensitized triplet-triplet annihilation, resulting in the conversion of low energy photons to higher energy light, thereby enabling numerous wavelength-shifting applications. Recent topical developments in upconversion include encapsulating or rigidifying fluid solutions to give them mechanical strength, adapting inert host materials to enable upconversion, and using photoactive materials that incorporate the sensitizer and/or the acceptor. The driving force behind translating photochemical upconversion from solution into hard and soft materials is the incorporation of upconversion into devices and other applications. At present, some of the most promising applications of upconversion materials include imaging and fluorescence microscopy, photoelectrochemical devices, water disinfection, and solar cell enhancement. PMID:27573144

  10. Materials of Gasification

    SciTech Connect

    2005-09-15

    The objective of this project was to accumulate and establish a database of construction materials, coatings, refractory liners, and transitional materials that are appropriate for the hardware and scale-up facilities for atmospheric biomass and coal gasification processes. Cost, fabricability, survivability, contamination, modes of corrosion, failure modes, operational temperatures, strength, and compatibility are all areas of materials science for which relevant data would be appropriate. The goal will be an established expertise of materials for the fossil energy area within WRI. This would be an effort to narrow down the overwhelming array of materials information sources to the relevant set which provides current and accurate data for materials selection for fossil fuels processing plant. A significant amount of reference material on materials has been located, examined and compiled. The report that describes these resources is well under way. The reference material is in many forms including texts, periodicals, websites, software and expert systems. The most important part of the labor is to refine the vast array of available resources to information appropriate in content, size and reliability for the tasks conducted by WRI and its clients within the energy field. A significant has been made to collate and capture the best and most up to date references. The resources of the University of Wyoming have been used extensively as a local and assessable location of information. As such, the distribution of materials within the UW library has been added as a portion of the growing document. Literature from recent journals has been combed for all pertinent references to high temperature energy based applications. Several software packages have been examined for relevance and usefulness towards applications in coal gasification and coal fired plant. Collation of the many located resources has been ongoing. Some web-based resources have been examined.

  11. Materials Research Capabilities

    NASA Technical Reports Server (NTRS)

    Stofan, Andrew J.

    1986-01-01

    Lewis Research Center, in partnership with U.S. industry and academia, has long been a major force in developing advanced aerospace propulsion and power systems. One key aspect that made many of these systems possible has been the availability of high-performance, reliable, and long-life materials. To assure a continuing flow of new materials and processing concepts, basic understanding to guide such innovation, and technological support for development of major NASA systems, Lewis has supported a strong in-house materials research activity. Our researchers have discovered new alloys, polymers, metallic composites, ceramics, coatings, processing techniques, etc., which are now also in use by U.S. industry. This brochure highlights selected past accomplishments of our materials research and technology staff. It also provides many examples of the facilities available with which we can conduct materials research. The nation is now beginning to consider integrating technology for high-performance supersonic/hypersonic aircraft, nuclear space power systems, a space station, and new research areas such as materials processing in space. As we proceed, I am confident that our materials research staff will continue to provide important contributions which will help our nation maintain a strong technology position in these areas of growing world competition. Lewis Research Center, in partnership with U.S. industry and academia, has long been a major force in developing advanced aerospace propulsion and power systems. One key aspect that made many of these systems possible has been the availability of high-performance, reliable, and long-life materials. To assure a continuing flow of new materials and processing concepts, basic understanding to guide such innovation, and technological support for development of major NASA systems, Lewis has supported a strong in-house materials research activity. Our researchers have discovered new alloys, polymers, metallic composites

  12. Cathode material for electrochemical cells

    SciTech Connect

    Ryan, D.M.

    1993-08-24

    A primary cell is described having an anode material, an electrolyte material and a cathode material, wherein said cathode material, in the predischarge condition thereof, is K[sub 3]V[sub 5]O[sub 14].

  13. The NASA/JPL Evaluation of Oxygen Interactions with Materials-3 (EOIM-3)

    NASA Technical Reports Server (NTRS)

    Brinza, David E.; Chung, Shirley Y.; Minton, Timothy K.; Liang, Ranty H.

    1994-01-01

    The deleterious effects of hyperthermal atomic oxygen (AO) found in low-earth-orbit (LEO) environments on critical flight materials has been known since early shuttle flights. This corrosive effect is of considerable concern because it compromises the performance and longevity of spacecraft/satellite materials deployed for extended periods in LEO. The NASA Evaluation of Oxygen Interactions with Materials-3 (EOIM-3) experiment served as a testbed for a variety of candidate flight materials for space assets. A total of 57 JPL test specimens were present in six subexperiments aboard EOIM-3. In addition to a number of passive exposure materials for flight and advanced technology programs, several subexperiments were included to provide data for understanding the details of atomic oxygen interactions with materials. Data and interpretations are presented for the heated tray, heated strips, solar ultraviolet exposure, and scatterometer subexperiments, along with a detailed description of the exposure conditions experienced by materials in the various experiments. Mass spectra of products emerging from identical samples of a (sup 13)C-enriched polyimide polymer (chemically equivalent to Kapton) under atomic oxygen bombardment in space and in the laboratory were collected. Reaction products unambiguously detected in space were (sup 13)CO, NO, (sup 12)CO2, and (sup 13)CO2. These reaction products and two others, H2O and (sup 12)CO, were detected in the laboratory, along with inelastically scattered atomic and molecular oxygen. Qualitative agreement was seen in the mass spectra taken in space and in the laboratory; the agreement may be improved by reducing the fraction of O2 in the laboratory molecular beam.

  14. Materials at LANL

    SciTech Connect

    Taylor, Antoinette J

    2010-01-01

    Exploring the physics, chemistry, and metallurgy of materials has been a primary focus of Los Alamos National Laboratory since its inception. In the early 1940s, very little was known or understood about plutonium, uranium, or their alloys. In addition, several new ionic, polymeric, and energetic materials with unique properties were needed in the development of nuclear weapons. As the Laboratory has evolved, and as missions in threat reduction, defense, energy, and meeting other emerging national challenges have been added, the role of materials science has expanded with the need for continued improvement in our understanding of the structure and properties of materials and in our ability to synthesize and process materials with unique characteristics. Materials science and engineering continues to be central to this Laboratory's success, and the materials capability truly spans the entire laboratory - touching upon numerous divisions and directorates and estimated to include >1/3 of the lab's technical staff. In 2006, Los Alamos and LANS LLC began to redefine our future, building upon the laboratory's established strengths and promoted by strongly interdependent science, technology and engineering capabilities. Eight Grand Challenges for Science were set forth as a technical framework for bridging across capabilities. Two of these grand challenges, Fundamental Understanding of Materials and Superconductivity and Actinide Science. were clearly materials-centric and were led out of our organizations. The complexity of these scientific thrusts was fleshed out through workshops involving cross-disciplinary teams. These teams refined the grand challenge concepts into actionable descriptions to be used as guidance for decisions like our LDRD strategic investment strategies and as the organizing basis for our external review process. In 2008, the Laboratory published 'Building the Future of Los Alamos. The Premier National Security Science Laboratory,' LA-UR-08

  15. NSUF Irradiated Materials Library

    SciTech Connect

    Cole, James Irvin

    2015-09-01

    The Nuclear Science User Facilities has been in the process of establishing an innovative Irradiated Materials Library concept for maximizing the value of previous and on-going materials and nuclear fuels irradiation test campaigns, including utilization of real-world components retrieved from current and decommissioned reactors. When the ATR national scientific user facility was established in 2007 one of the goals of the program was to establish a library of irradiated samples for users to access and conduct research through competitively reviewed proposal process. As part of the initial effort, staff at the user facility identified legacy materials from previous programs that are still being stored in laboratories and hot-cell facilities at the INL. In addition other materials of interest were identified that are being stored outside the INL that the current owners have volunteered to enter into the library. Finally, over the course of the last several years, the ATR NSUF has irradiated more than 3500 specimens as part of NSUF competitively awarded research projects. The Logistics of managing this large inventory of highly radioactive poses unique challenges. This document will describe materials in the library, outline the policy for accessing these materials and put forth a strategy for making new additions to the library as well as establishing guidelines for minimum pedigree needed to be included in the library to limit the amount of material stored indefinitely without identified value.

  16. Materials science and engineering

    SciTech Connect

    Holden, T.M.

    1995-10-01

    The science-based stockpile stewardship program emphasizes a better understanding of how complex components function through advanced computer calculations. Many of the problem areas are in the behavior of materials making up the equipment. The Los Alamos Neutron Science Center (LANSCE) can contribute to solving these problems by providing diagnostic tools to examine parts noninvasively and by providing the experimental tools to understand material behavior in terms of both the atomic structure and the microstructure. Advanced computer codes need experimental information on material behavior in response to stress, temperature, and pressure as input, and they need benchmarking experiments to test the model predictions for the finished part.

  17. Materials for syngas coolers

    NASA Astrophysics Data System (ADS)

    Perkins, R. A.; Morse, G.; Coons, W. C.

    1982-08-01

    A technical basis for materials selection and laboratory testing of practical boiler tube materials which will provide reliable long term service in syngas coolers for coal gasification combined cycle power plants is outlined. The resistance of low alloy steel, stainless steels, and aluminum rich coatings to attach by a high sulfur, medium Btu coal gasification atmosphere was evaluated at 300 to 500 deg C. The materials may have adequate resistance for long time service in radiant coolers operating up to 500 deg C on high sulfur medium Btu gas. Performance is analyzed for thermodynamic and kinetic properties and recommendations for long term tests and development of protective coatings are presented.

  18. Electrically conductive composite material

    DOEpatents

    Clough, R.L.; Sylwester, A.P.

    1988-06-20

    An electrically conductive composite material is disclosed which comprises a conductive open-celled, low density, microcellular carbon foam filled with a non-conductive polymer or resin. The composite material is prepared in a two-step process consisting of first preparing the microcellular carbon foam from a carbonizable polymer or copolymer using a phase separation process, then filling the carbon foam with the desired non-conductive polymer or resin. The electrically conductive composites of the present invention has a uniform and consistent pattern of filler distribution, and as a result is superior over prior art materials when used in battery components, electrodes, and the like. 2 figs.

  19. Material Challenges and Perspectives

    SciTech Connect

    Choi, Daiwon; Wang, Wei; Yang, Zhenguo

    2011-12-14

    General history and principals of Li-ion battery, characterization techniques and terminology of its operation will be discussed and explained. Current Li-ion battery applications and comparison to other energy storage and conversion systems will be outlined. Chemistry, material and design of currently commercialized Li-ion batteries will be discussed including various electrode materials for cathodes and anodes. The electrode material candidates and its physical and chemical properties including crystal structure, capacity, cycling stability, cost and safety. Also, current limitations of Li-ion batteries will be discussed.

  20. Electrically conductive composite material

    DOEpatents

    Clough, Roger L.; Sylwester, Alan P.

    1989-01-01

    An electrically conductive composite material is disclosed which comprises a conductive open-celled, low density, microcellular carbon foam filled with a non-conductive polymer or resin. The composite material is prepared in a two-step process consisting of first preparing the microcellular carbon foam from a carbonizable polymer or copolymer using a phase separation process, then filling the carbon foam with the desired non-conductive polymer or resin. The electrically conductive composites of the present invention has a uniform and consistant pattern of filler distribution, and as a result is superior over prior art materials when used in battery components, electrodes, and the like.

  1. ATS materials/manufacturing

    SciTech Connect

    Karnitz, M.A.; Wright, I.G.; Ferber, M.K.

    1997-11-01

    The Materials/Manufacturing Technology subelement is a part of the base technology portion of the Advanced Turbine Systems (ATS) Program. The work in this subelement is being performed predominantly by industry with assistance from national laboratories and universities. The projects in this subelement are aimed toward hastening the incorporation of new materials and components in gas turbines. Work is currently ongoing on thermal barrier coatings (TBCs), the scale-up of single crystal airfoil manufacturing technologies, materials characterization, and technology information exchange. This paper presents highlights of the activities during the past year. 12 refs., 24 figs., 4 tabs.

  2. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Loewy, R.; Wiberley, S. E.

    1986-01-01

    Overall emphasis is on basic long-term research in the following categories: constituent materials, composite materials, generic structural elements, processing science technology; and maintaining long-term structural integrity. Research in basic composition, characteristics, and processing science of composite materials and their constituents is balanced against the mechanics, conceptual design, fabrication, and testing of generic structural elements typical of aerospace vehicles so as to encourage the discovery of unusual solutions to present and future problems. Detailed descriptions of the progress achieved in the various component parts of this comprehensive program are presented.

  3. Biomedical materials and devices

    SciTech Connect

    Hanker, J. S. ); Giammara, B. L. )

    1989-01-01

    This conference reports on how biomedical materials and devices are undergoing important changes that require interdisciplinary approaches, innovation expertise, and access to sophisticated preparative and analytical equipment and methodologies. The interaction of materials scientists with biomedical, biotechnological, bioengineering and clinical scientists in the last decade has resulted in major advances in therapy. New therapeutic modalities and bioengineering methods and devices for the continuous removal of toxins or pathologic products present in arthritis, atherosclerosis and malignancy are presented. Novel monitoring and controlled drug delivery systems and discussions of materials such as blood or plasma substitutes, artificial organs, and bone graft substitutes are discussed.

  4. Investigating Encrypted Material

    NASA Astrophysics Data System (ADS)

    McGrath, Niall; Gladyshev, Pavel; Kechadi, Tahar; Carthy, Joe

    When encrypted material is discovered during a digital investigation and the investigator cannot decrypt the material then s/he is faced with the problem of how to determine the evidential value of the material. This research is proposing a methodology of extracting probative value from the encrypted file of a hybrid cryptosystem. The methodology also incorporates a technique for locating the original plaintext file. Since child pornography (KP) images and terrorist related information (TI) are transmitted in encrypted format the digital investigator must ask the question Cui Bono? - who benefits or who is the recipient? By doing this the scope of the digital investigation can be extended to reveal the intended recipient.

  5. Fissile material detector

    DOEpatents

    Ivanov, Alexander I.; Lushchikov, Vladislav I.; Shabalin, Eugeny P.; Maznyy, Nikita G.; Khvastunov, Michael M.; Rowland, Mark

    2002-01-01

    A detector for fissile materials which provides for integrity monitoring of fissile materials and can be used for nondestructive assay to confirm the presence of a stable content of fissile material in items. The detector has a sample cavity large enough to enable assay of large items of arbitrary configuration, utilizes neutron sources fabricated in spatially extended shapes mounted on the endcaps of the sample cavity, incorporates a thermal neutron filter insert with reflector properties, and the electronics module includes a neutron multiplicity coincidence counter.

  6. Gravity and Granular Materials

    NASA Technical Reports Server (NTRS)

    Behringer, R. P.; Hovell, Daniel; Kondic, Lou; Tennakoon, Sarath; Veje, Christian

    1999-01-01

    We describe experiments that probe a number of different types of granular flow where either gravity is effectively eliminated or it is modulated in time. These experiments include the shaking of granular materials both vertically and horizontally, and the shearing of a 2D granular material. For the shaken system, we identify interesting dynamical phenomena and relate them to standard simple friction models. An interesting application of this set of experiments is to the mixing of dissimilar materials. For the sheared system we identify a new kind of dynamical phase transition.

  7. Encapsulation materials research

    NASA Technical Reports Server (NTRS)

    Willis, P. B.

    1984-01-01

    Encapsulation materials for solar cells were investigated. The different phases consisted of: (1) identification and development of low cost module encapsulation materials; (2) materials reliability examination; and (3) process sensitivity and process development. It is found that outdoor photothermal aging devices (OPT) are the best accelerated aging methods, simulate worst case field conditions, evaluate formulation and module performance and have a possibility for life assessment. Outdoor metallic copper exposure should be avoided, self priming formulations have good storage stability, stabilizers enhance performance, and soil resistance treatment is still effective.

  8. Piezoelectric composite materials

    NASA Technical Reports Server (NTRS)

    Kiraly, L. J. (Inventor)

    1983-01-01

    A laminated structural devices has the ability to change shape, position and resonant frequency without using discrete motive components. The laminate may be a combination of layers of a piezoelectrically active, nonconductive matrix material. A power source selectively places various levels of charge in electrically conductive filaments imbedded in the respective layers to produce various configurations in a predetermined manner. The layers may be electrically conductive having imbedded piezoelectrically active filaments. A combination of layers of electrically conductive material may be laminated to layers of piezoelectrically active material.

  9. Composite Structural Materials

    NASA Technical Reports Server (NTRS)

    Ansell, G. S.; Loewy, R. G.; Wiberly, S. E.

    1984-01-01

    The development and application of filamentary composite materials, is considered. Such interest is based on the possibility of using relatively brittle materials with high modulus, high strength, but low density in composites with good durability and high tolerance to damage. Fiber reinforced composite materials of this kind offer substantially improved performance and potentially lower costs for aerospace hardware. Much progress has been made since the initial developments in the mid 1960's. There were only limited applied to the primary structure of operational vehicles, mainly as aircrafts.

  10. Asymmetric Diffusional Solidification during Transient Liquid Phase Bonding of Dissimilar Materials

    NASA Astrophysics Data System (ADS)

    Ghoneim, A.; Ojo, O. A.

    2012-03-01

    A theoretical analysis of diffusional solidification during transient liquid phase (TLP) bonding of dissimilar materials was performed in conjunction with experimental verification. A fully implicit, two-dimensional, finite element numerical simulation model, without the inherent symmetry assumption, was developed and used for the theoretical calculations, and good correlations between the model predictions and experimental results were observed. The study showed that an asymmetric distribution of residual interlayer liquid during a dissimilar joining of polycrystal and single crystal alloys is attributable to a mismatch between their lattice diffusion coefficients or solute solubility, irrespective of enhanced intergranular diffusion as was assumed previously. Also, notwithstanding increased solute diffusivity with temperature, it was found that an increase in bonding temperature can result in the prolongation of processing time t f that is required to prevent the formation of deleterious eutectic during bonding of dissimilar materials. The occurrence of this seemingly anomalous behavior, however, reduces when a material is coupled with another type that exhibits a higher solute solubility or better capability of accommodating diffusing melting point depressant solute from the liquid interlayer.

  11. Measuring the diffusion of Ti and Cu in low-k materials for microelectronic devices by EELS, EFTEM and EDX

    NASA Astrophysics Data System (ADS)

    Barnes, J.-P.; Lafond, D.; Guedj, C.; Fayolle, M.; Meininger, P.; Maitrejean, S.; David, T.; Possémé, N.; Bayle-Guillemaud, P.; Chabli, Amal

    2006-02-01

    The need to reduce RC delay and cross talk in Cu interconnects means that ultra low-k dielectrics such as porous SiCOH are being integrated into microelectronic devices. Unfortunately porous materials lead to integration issues such as metal diffusion into the porosity of the dielectric, especially when chemical vapour deposition (CVD) methods are used for metal deposition. In our case, the copper anti-diffusion barrier used before Cu deposition is MOCVD TiN. Without an appropriate surface treatment (pore sealing) of the low-k the TiN may diffuse in the porosity. The presence of Ti or Cu in the low-k is deleterious as it can raise the dielectric constant and the leakage current. EFTEM EELS and EDX have been used to map Ti, Cu, O and C as a function of process conditions.

  12. Cookoff of energetic materials

    SciTech Connect

    Baer, M.R.; Hobbs, M.L.; Gross, R.J.; Schmitt, R.G.

    1998-09-01

    An overview of cookoff modeling at Sandia National Laboratories is presented aimed at assessing the violence of reaction following cookoff of confined energetic materials. During cookoff, the response of energetic materials is known to involve coupled thermal/chemical/mechanical processes which induce thermal damage to the energetic material prior to the onset of ignition. These damaged states enhance shock sensitivity and lead to conditions favoring self-supported accelerated combustion. Thus, the level of violence depends on the competition between pressure buildup and stress release due to the loss of confinement. To model these complex processes, finite element-based analysis capabilities are being developed which can resolve coupled heat transfer with chemistry, quasi-static structural mechanics and dynamic response. Numerical simulations that assess the level of violence demonstrate the importance of determining material damage in pre- and post-ignition cookoff events.

  13. Materials research at CMAM

    SciTech Connect

    Zucchiatti, Alessandro

    2013-07-18

    The Centro de Micro Analisis de Materiales (CMAM) is a research centre of the Universidad Autonoma de Madrid dedicated to the modification and analysis of materials using ion beam techniques. The infrastructure, based on a HVEE 5MV tandem accelerator, provided with a coaxial Cockcroft Walton charging system, is fully open to research groups of the UAM, to other public research institutions and to private enterprises. The CMAM research covers a few important lines such as advanced materials, surface science, biomedical materials, cultural heritage, materials for energy production. The Centre gives as well support to university teaching and technical training. A detail description of the research infrastructures and their use statistics will be given. Some of the main research results will be presented to show the progress of research in the Centre in the past few years and to motivate the strategic plans for the forthcoming.

  14. Heavy Vehicle Propulsion Materials

    SciTech Connect

    Ray Johnson

    2000-01-31

    The objectives are to Provide Key Enabling Materials Technologies to Increase Energy Efficiency and Reduce Exhaust Emissions. The following goals are listed: Goal 1: By 3rd quarter 2002, complete development of materials enabling the maintenance or improvement of fuel efficiency {ge} 45% of class 7-8 truck engines while meeting the EPA/Justice Department ''Consent Decree'' for emissions reduction. Goal 2: By 4th quarter 2004, complete development of enabling materials for light-duty (class 1-2) diesel truck engines with efficiency over 40%, over a wide range of loads and speeds, while meeting EPA Tier 2 emission regulations. Goal 3: By 4th quarter 2006, complete development of materials solutions to enable heavy-duty diesel engine efficiency of 50% while meeting the emission reduction goals identified in the EPA proposed rule for heavy-duty highway engines.''

  15. Materials engineering data base

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The various types of materials related data that exist at the NASA Marshall Space Flight Center and compiled into databases which could be accessed by all the NASA centers and by other contractors, are presented.

  16. Degradation of Spacecraft Materials

    NASA Technical Reports Server (NTRS)

    Dever, Joyce; Banks, Bruce; deGroh, Kim; Miller, Sharon

    2004-01-01

    This chapter includes descriptions of specific space environmental threats to exterior spacecraft materials. The scope will be confined to effects on exterior spacecraft surfaces, and will not, therefore, address environmental effects on interior spacecraft systems, such as electronics. Space exposure studies and laboratory simulations of individual and combined space environemntal threats will be summarized. A significant emphasis is placed on effects of Earth orbit environments, because the majority of space missions have been flown in Earth orbits which have provided a significant amount of data on materials effects. Issues associated with interpreting materials degradation results will be discussed, and deficiencies of ground testing will be identified. Recommendations are provided on reducing or preventing space environmental degradation through appropriate materials selection.

  17. Holographic Recording Materials Development

    NASA Technical Reports Server (NTRS)

    Verber, C. M.; Schwerzel, R. E.; Perry, P. J.; Craig, R. A.

    1976-01-01

    Organic photorefractive materials were evaluated for application in a reversible holographic memory system. Representative indigo and thioindigo derivatives and several stilbene derivatives were studied as well as 15, 16-dialkyldihydropyrene derivatives the following goals were achieved: (1) the successful writing of phase holograms in a thioindigo/polymer gel system, (2) the successful writing and erasing of phase holograms in a variety of indigo/polymer gel and indigo/solid polymer systems, and (3) the identification of indigoid dyes and 15, 16-dialkyldihydropyrene derivatives as materials potentially suitable for utilization in an operational system. Photochemical studies of the stilbene, indigo, thioindigo, and dialkyldihydropyrene derivatives in solution and in a variety of polymer matrix materials were conducted with the goal of optimizing the photorefractive behavior of the chemical system as a whole. The spectroscopic properties required of optimal photorefractive materials were identified, and it was shown that both the indigoid dyes and the dialkyldihydropyrenes closely match the required properties.

  18. Dental obturation materials

    NASA Astrophysics Data System (ADS)

    Stockton, Elizabeth; Chudej, Lauren; Bilyeu, Brian; Brostow, Witold

    2006-10-01

    During the last decades, people have tried to develop a better material for use in dental obturation materials. This new material should meet the following requirements: durability, wear resistance, biocompatibility and chemical adhesion to dentin enamel. Wear resistance is very important and it is related with the service life of dental replacements. We have obtained aesthetically promising novel nano composites that can be used as dental replacements. The main objective of this work is to study the scratch and wear resistance of these nano composites. To meet this goal, scratch tests are performed using a micro scratch tester machine (CSEM), where a diamond indenter is used to make the scratch and the penetration of this indenter is measured with high resolution (7nm). We will be looking at the penetration depth (Rp) and the residual (or healing) depth (Rh) to calculate the percent recovery. These measurements represent the scratch resistance of the material.

  19. Building Materials Property Table

    SciTech Connect

    2010-04-16

    This information sheet describes a table of some of the key technical properties of many of the most common building materials taken from ASHRAE Fundamentals - 2001, Moisture Control in Buildings, CMHC, NRC/IRC, IEA Annex 24, and manufacturer data.

  20. Lunar material transport vehicle

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Lyons, Douglas; Wilkins, W. Allen, Jr.; Whitehead, Harry C., Jr.

    1988-01-01

    The proposed vehicle, the Lunar Material Transport Vehicle (LMTV), has a mission objective of efficient lunar soil material transport. The LMTV was designed to meet a required set of performance specifications while operating under a given set of constraints. The LMTV is essentially an articulated steering, double-ended dump truck. The vehicle moves on four wheels and has two identical chassis halves. Each half consists of a chassis frame, a material bucket, two wheels with integral curvilinear synchronous motors, a fuel cell and battery arrangement, an electromechanically actuated dumping mechanism, and a powerful microprocessor. The vehicle, as designed, is capable of transporting up to 200 cu ft of material over a one mile round trip per hour. The LMTV is capable of being operated from a variety of sources. The vehicle has been designed as simply as possible with attention also given to secondary usage of components.

  1. Electrically conductive material

    DOEpatents

    Singh, J.P.; Bosak, A.L.; McPheeters, C.C.; Dees, D.W.

    1993-09-07

    An electrically conductive material is described for use in solid oxide fuel cells, electrochemical sensors for combustion exhaust, and various other applications possesses increased fracture toughness over available materials, while affording the same electrical conductivity. One embodiment of the sintered electrically conductive material consists essentially of cubic ZrO[sub 2] as a matrix and 6-19 wt. % monoclinic ZrO[sub 2] formed from particles having an average size equal to or greater than about 0.23 microns. Another embodiment of the electrically conductive material consists essentially at cubic ZrO[sub 2] as a matrix and 10-30 wt. % partially stabilized zirconia (PSZ) formed from particles having an average size of approximately 3 microns. 8 figures.

  2. Electrically conductive material

    DOEpatents

    Singh, Jitendra P.; Bosak, Andrea L.; McPheeters, Charles C.; Dees, Dennis W.

    1993-01-01

    An electrically conductive material for use in solid oxide fuel cells, electrochemical sensors for combustion exhaust, and various other applications possesses increased fracture toughness over available materials, while affording the same electrical conductivity. One embodiment of the sintered electrically conductive material consists essentially of cubic ZrO.sub.2 as a matrix and 6-19 wt. % monoclinic ZrO.sub.2 formed from particles having an average size equal to or greater than about 0.23 microns. Another embodiment of the electrically conductive material consists essentially at cubic ZrO.sub.2 as a matrix and 10-30 wt. % partially stabilized zirconia (PSZ) formed from particles having an average size of approximately 3 microns.

  3. Dynamics of Granular Materials

    NASA Technical Reports Server (NTRS)

    Behringer, Robert P.

    1996-01-01

    Granular materials exhibit a rich variety of dynamical behavior, much of which is poorly understood. Fractal-like stress chains, convection, a variety of wave dynamics, including waves which resemble capillary waves, l/f noise, and fractional Brownian motion provide examples. Work beginning at Duke will focus on gravity driven convection, mixing and gravitational collapse. Although granular materials consist of collections of interacting particles, there are important differences between the dynamics of a collections of grains and the dynamics of a collections of molecules. In particular, the ergodic hypothesis is generally invalid for granular materials, so that ordinary statistical physics does not apply. In the absence of a steady energy input, granular materials undergo a rapid collapse which is strongly influenced by the presence of gravity. Fluctuations on laboratory scales in such quantities as the stress can be very large-as much as an order of magnitude greater than the mean.

  4. Instrumentation for Materials Research

    ERIC Educational Resources Information Center

    Claassen, Richard S.

    1976-01-01

    Discusses how sophisticated instrumentation techniques yield practical results in three typical materials problems: fracture analysis, joining, and compatibility. Describes techniques such as scanning and transmission electron microscopy, and Auger spectroscopy. (MLH)

  5. Mesoporous carbon materials

    SciTech Connect

    Dai, Sheng; Wang, Xiqing

    2012-02-14

    The invention is directed to a method for fabricating a mesoporous carbon material, the method comprising subjecting a precursor composition to a curing step followed by a carbonization step, the precursor composition comprising: (i) a templating component comprised of a block copolymer, (ii) a phenolic compound or material, (iii) a crosslinkable aldehyde component, and (iv) at least 0.5 M concentration of a strong acid having a pKa of or less than -2, wherein said carbonization step comprises heating the precursor composition at a carbonizing temperature for sufficient time to convert the precursor composition to a mesoporous carbon material. The invention is also directed to a mesoporous carbon material having an improved thermal stability, preferably produced according to the above method.

  6. Magnetocaloric materials: Strained relations

    NASA Astrophysics Data System (ADS)

    Nordblad, Per

    2013-01-01

    The magnetocaloric effect could form the basis for efficient refrigeration technologies. The finding that large and reversible magnetocaloric effects can be induced through a strain-mediated feedback mechanism may expand the range of available magnetocaloric materials.

  7. Ceramic breeder materials

    SciTech Connect

    Johnson, C.E.

    1990-01-01

    The breeding blanket is a key component of the fusion reactor because it directly involves tritium breeding and energy extraction, both of which are critical to development of fusion power. The lithium ceramics continue to show promise as candidate breeder materials. This promise was recognized by the International Thermonuclear Reactor (ITER) design team in its selection of ceramics as the first option for the ITER breeder material. Blanket design studies have indicated properties in the candidate materials data base that need further investigation. Current studies are focusing on tritium release behavior at high burnup, changes in thermophysical properties with burnup, compatibility between the ceramic breeder and beryllium multiplier, and phase changes with burnup. Laboratory and in-reactor tests, some as part of an international collaboration for development of ceramic breeder materials, are underway. 32 refs., 1 fig., 1 tab.

  8. Nuclear material operations manual

    SciTech Connect

    Tyler, R.P.

    1981-02-01

    This manual provides a concise and comprehensive documentation of the operating procedures currently practiced at Sandia National Laboratories with regard to the management, control, and accountability of nuclear materials. The manual is divided into chapters which are devoted to the separate functions performed in nuclear material operations-management, control, accountability, and safeguards, and the final two chapters comprise a document which is also issued separately to provide a summary of the information and operating procedures relevant to custodians and users of radioactive and nuclear materials. The manual also contains samples of the forms utilized in carrying out nuclear material activities. To enhance the clarity of presentation, operating procedures are presented in the form of playscripts in which the responsible organizations and necessary actions are clearly delineated in a chronological fashion from the initiation of a transaction to its completion.

  9. Unusual spacecraft materials

    NASA Technical Reports Server (NTRS)

    Post, Jonathan V.

    1990-01-01

    For particularly innovative space exploration missions, unusual requirements are levied on the structural components of the spacecraft. In many cases, the preferred solution is the utilization of unusual materials. This trend is forecast to continue. Several hypothetic examples are discussed.

  10. Reversible hydrogen storage materials

    DOEpatents

    Ritter, James A.; Wang, Tao; Ebner, Armin D.; Holland, Charles E.

    2012-04-10

    In accordance with the present disclosure, a process for synthesis of a complex hydride material for hydrogen storage is provided. The process includes mixing a borohydride with at least one additive agent and at least one catalyst and heating the mixture at a temperature of less than about 600.degree. C. and a pressure of H.sub.2 gas to form a complex hydride material. The complex hydride material comprises MAl.sub.xB.sub.yH.sub.z, wherein M is an alkali metal or group IIA metal, Al is the element aluminum, x is any number from 0 to 1, B is the element boron, y is a number from 0 to 13, and z is a number from 4 to 57 with the additive agent and catalyst still being present. The complex hydride material is capable of cyclic dehydrogenation and rehydrogenation and has a hydrogen capacity of at least about 4 weight percent.

  11. Tough Composite Materials

    NASA Technical Reports Server (NTRS)

    Vosteen, L. F. (Compiler); Johnson, N. J. (Compiler); Teichman, L. A. (Compiler)

    1984-01-01

    Papers and working group summaries are presented which address composite material behavior and performance improvement. Topic areas include composite fracture toughness and impact characterization, constituent properties and interrelationships, and matrix synthesis and characterization.

  12. Photoconductivity in Dirac materials

    SciTech Connect

    Shao, J. M.; Yang, G. W.

    2015-11-15

    Two-dimensional (2D) Dirac materials including graphene and the surface of a three-dimensional (3D) topological insulator, and 3D Dirac materials including 3D Dirac semimetal and Weyl semimetal have attracted great attention due to their linear Dirac nodes and exotic properties. Here, we use the Fermi’s golden rule and Boltzmann equation within the relaxation time approximation to study and compare the photoconductivity of Dirac materials under different far- or mid-infrared irradiation. Theoretical results show that the photoconductivity exhibits the anisotropic property under the polarized irradiation, but the anisotropic strength is different between 2D and 3D Dirac materials. The photoconductivity depends strongly on the relaxation time for different scattering mechanism, just like the dark conductivity.

  13. Materials research at CMAM

    NASA Astrophysics Data System (ADS)

    Zucchiatti, Alessandro

    2013-07-01

    The Centro de Micro Analisis de Materiales (CMAM) is a research centre of the Universidad Autónoma de Madrid dedicated to the modification and analysis of materials using ion beam techniques. The infrastructure, based on a HVEE 5MV tandem accelerator, provided with a coaxial Cockcroft Walton charging system, is fully open to research groups of the UAM, to other public research institutions and to private enterprises. The CMAM research covers a few important lines such as advanced materials, surface science, biomedical materials, cultural heritage, materials for energy production. The Centre gives as well support to university teaching and technical training. A detail description of the research infrastructures and their use statistics will be given. Some of the main research results will be presented to show the progress of research in the Centre in the past few years and to motivate the strategic plans for the forthcoming.

  14. Materials engineering for immunomodulation.

    PubMed

    Hubbell, Jeffrey A; Thomas, Susan N; Swartz, Melody A

    2009-11-26

    The engineering of materials that can modulate the immune system is an emerging field that is developing alongside immunology. For therapeutic ends such as vaccine development, materials are now being engineered to deliver antigens through specific intracellular pathways, allowing better control of the way in which antigens are presented to one of the key types of immune cell, T cells. Materials are also being designed as adjuvants, to mimic specific 'danger' signals in order to manipulate the resultant cytokine environment, which influences how antigens are interpreted by T cells. In addition to offering the potential for medical advances, immunomodulatory materials can form well-defined model systems, helping to provide new insight into basic immunobiology.

  15. CHARACTERIZATION OF DAMAGED MATERIALS

    SciTech Connect

    Hsu, P C; Dehaven, M; McClelland, M; Chidester, S; Maienschein, J L

    2006-06-23

    Thermal damage experiments were conducted on LX-04, LX-10, and LX-17 at high temperatures. Both pristine and damaged samples were characterized for their material properties. A pycnometer was used to determine sample true density and porosity. Gas permeability was measured in a newly procured system (diffusion permeameter). Burn rate was measured in the LLNL strand burner. Weight losses upon thermal exposure were insignificant. Damaged pressed parts expanded, resulting in a reduction of bulk density by up to 10%. Both gas permeabilities and burn rates of the damaged samples increased by several orders of magnitude due to higher porosity and lower density. Moduli of the damaged materials decreased significantly, an indication that the materials became weaker mechanically. Damaged materials were more sensitive to shock initiation at high temperatures. No significant sensitization was observed when the damaged samples were tested at room temperature.

  16. Computational Materials Research

    NASA Technical Reports Server (NTRS)

    Veazie, David R.

    1998-01-01

    High temperature thermoplastic polyimide polymers are incorporated in engineering structures in the form of matrix materials in advanced fiber composites and adhesives in bonded joints. Developing analytical tools to predict long term performance and screen for final materials selection for polymers is the impetus for intensive studies at NASA and major industry based airframe developers. These fiber-reinforced polymeric composites (FRPCs) combine high strength with lightweight. In addition, they offer corrosion and fatigue resistance, a reduction in parts count, and new possibilities for control through aeroelastic tailoring and "smart" structures containing fully-integrated sensors and actuators. However, large-scale acceptance and use of polymer composites has historically been extremely slow. Reasons for this include a lack of familiarity of designers with the materials; the need for new tooling and new inspection and repair infrastructures; and high raw materials and fabrication costs.

  17. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Ansell, G. S.; Loewy, R. G.; Wiberley, S. E.

    1979-01-01

    Technology utilization of fiber reinforced composite materials is discussed in the areas of physical properties, and life prediction. Programs related to the Composite Aircraft Program are described in detail.

  18. Moldable cork ablation material

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A successful thermal ablative material was manufactured. Moldable cork sheets were tested for density, tensile strength, tensile elongation, thermal conductivity, compression set, and specific heat. A moldable cork sheet, therefore, was established as a realistic product.

  19. LIST OF INSTRUCTIONAL MATERIALS.

    ERIC Educational Resources Information Center

    Tennessee State Dept. of Education, Nashville.

    PRICES ARE GIVEN FOR MATERIALS FOR AGRICULTURE EDUCATION, HEALTH OCCUPATIONS EDUCATION, DISTRIBUTIVE EDUCATION, MANPOWER DEVELOPMENT AND TRAINING PROGRAMS, AND TRADE AND INDUSTRIAL EDUCATION. THESE INCLUDE COURSES OF STUDY, LESSON PLANS, TEST AND ANSWER BOOKLETS, ASSIGNMENT SHEETS, AND TEACHER HANDBOOKS. (EL)

  20. Quasicrystals: Making invisible materials

    NASA Astrophysics Data System (ADS)

    Boriskina, Svetlana V.

    2015-07-01

    All-dielectric photonic quasicrystals may act as zero-refractive-index homogeneous materials despite their lack of translational symmetry and periodicity, stretching wavelengths to infinity and offering applications in light wavefront sculpting and optical cloaking.

  1. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Ansell, G. S.; Loewy, R. G.; Wiberley, S. E.

    1984-01-01

    Progress is reported in studies of constituent materials composite materials, generic structural elements, processing science technology, and maintaining long-term structural integrity. Topics discussed include: mechanical properties of high performance carbon fibers; fatigue in composite materials; experimental and theoretical studies of moisture and temperature effects on the mechanical properties of graphite-epoxy laminates and neat resins; numerical investigations of the micromechanics of composite fracture; delamination failures of composite laminates; effect of notch size on composite laminates; improved beam theory for anisotropic materials; variation of resin properties through the thickness of cured samples; numerical analysis composite processing; heat treatment of metal matrix composites, and the RP-1 and RP2 gliders of the sailplane project.

  2. Composite structural materials

    NASA Technical Reports Server (NTRS)

    Ansell, G. S.; Loewy, R. G.; Wiberley, S. E.

    1982-01-01

    The promise of filamentary composite materials, whose development may be considered as entering its second generation, continues to generate intense interest and applications activity. Fiber reinforced composite materials offer substantially improved performance and potentially lower costs for aerospace hardware. Much progress has been achieved since the initial developments in the mid 1960's. Rather limited applications to primary aircraft structure have been made, however, mainly in a material-substitution mode on military aircraft, except for a few experiments currently underway on large passenger airplanes in commercial operation. To fulfill the promise of composite materials completely requires a strong technology base. NASA and AFOSR recognize the present state of the art to be such that to fully exploit composites in sophisticated aerospace structures, the technology base must be improved. This, in turn, calls for expanding fundamental knowledge and the means by which it can be successfully applied in design and manufacture.

  3. Wth Basic Art Materials

    ERIC Educational Resources Information Center

    Herberholz, Barbara

    2010-01-01

    In this article, the author presents a checklist of basic materials for two-dimensional activities that are necessary for an elementary-school art program. She also provides a few tips on how to use them.

  4. Developments in carbon materials

    NASA Technical Reports Server (NTRS)

    Burchell, Timothy D.

    1994-01-01

    The following carbon-based materials are reviewed and their applications discussed: fullerenes; graphite (synthetic and manufactured); activated carbon fibers; and carbon-carbon composites. Carbon R&D activities at ORNL are emphasized.

  5. Nano-composite materials

    DOEpatents

    Lee, Se-Hee; Tracy, C. Edwin; Pitts, J. Roland

    2010-05-25

    Nano-composite materials are disclosed. An exemplary method of producing a nano-composite material may comprise co-sputtering a transition metal and a refractory metal in a reactive atmosphere. The method may also comprise co-depositing a transition metal and a refractory metal composite structure on a substrate. The method may further comprise thermally annealing the deposited transition metal and refractory metal composite structure in a reactive atmosphere.

  6. Concise polymeric materials encyclopedia

    SciTech Connect

    Salamone, J.C.

    1999-01-01

    This comprehensive, accessible resource abridges the ``Polymeric Materials Encyclopedia'', presenting more than 1,100 articles and featuring contributions from more than 1,800 scientists from all over the world. The text discusses a vast array of subjects related to the: (1) synthesis, properties, and applications of polymeric materials; (2) development of modern catalysts in preparing new or modified polymers; (3) modification of existing polymers by chemical and physical processes; and (4) biologically oriented polymers.

  7. Ceramic Laser Materials

    SciTech Connect

    Soules, T F; Clapsaddle, B J; Landingham, R L; Schaffers, K I

    2005-02-15

    Transparent ceramic materials have several major advantages over single crystals in laser applications, not the least of which is the ability to make large aperture parts in a robust manufacturing process. After more than a decade of working on making transparent YAG:Nd, Japanese workers have recently succeeded in demonstrating samples that performed as laser gain media as well as their single crystal counterparts. Since then several laser materials have been made and evaluated. For these reasons, developing ceramic laser materials is the most exciting and futuristic materials topic in today's major solid-state laser conferences. We have established a good working relationship with Konoshima Ltd., the Japanese producer of the best ceramic laser materials, and have procured and evaluated slabs designed by us for use in our high-powered SSHCL. Our measurements indicate that these materials will work in the SSHCL, and we have nearly completed retrofitting the SSHCL with four of the largest transparent ceramic YAG:Nd slabs in existence. We have also begun our own effort to make this material and have produced samples with various degrees of transparency/translucency. We are in the process of carrying out an extensive design-of-experiments to establish the significant process variables for making transparent YAG. Finally because transparent ceramics afford much greater flexibility in the design of lasers, we have been exploring the potential for much larger apertures, new materials, for example for the Mercury laser, other designs for SSHL, such as, edge pumping designs, slabs with built in ASE suppression, etc. This work has just beginning.

  8. NMR imaging of materials

    SciTech Connect

    Vinegar, H.J.; Rothwell, W.P.

    1988-03-01

    A method for obtaining at least one petrophysical property of a porous material containing therein at least one preselected fluid, is described, comprising: NMR imaging the material to generate signals dependent upon both M(0) and T/sub 1/ and M(0) and T/sub 2/, generating separate M(0), T/sub 1/ and T/sub 2/ images from the signals, and determining at least one petrophysical property from at least one of the images.

  9. Food Packaging Materials

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The photos show a few of the food products packaged in Alure, a metallized plastic material developed and manufactured by St. Regis Paper Company's Flexible Packaging Division, Dallas, Texas. The material incorporates a metallized film originally developed for space applications. Among the suppliers of the film to St. Regis is King-Seeley Thermos Company, Winchester, Ma'ssachusetts. Initially used by NASA as a signal-bouncing reflective coating for the Echo 1 communications satellite, the film was developed by a company later absorbed by King-Seeley. The metallized film was also used as insulating material for components of a number of other spacecraft. St. Regis developed Alure to meet a multiple packaging material need: good eye appeal, product protection for long periods and the ability to be used successfully on a wide variety of food packaging equipment. When the cost of aluminum foil skyrocketed, packagers sought substitute metallized materials but experiments with a number of them uncovered problems; some were too expensive, some did not adequately protect the product, some were difficult for the machinery to handle. Alure offers a solution. St. Regis created Alure by sandwiching the metallized film between layers of plastics. The resulting laminated metallized material has the superior eye appeal of foil but is less expensive and more easily machined. Alure effectively blocks out light, moisture and oxygen and therefore gives the packaged food long shelf life. A major packaging firm conducted its own tests of the material and confirmed the advantages of machinability and shelf life, adding that it runs faster on machines than materials used in the past and it decreases product waste; the net effect is increased productivity.

  10. Nonmetallic Materials Handbook

    NASA Technical Reports Server (NTRS)

    1974-01-01

    A handbook compilation of chemical and physical property tests data obtained during qualification and receiving inspection testing of nonmetallic materials for the Viking Lander is introduced. Data cover the following materials: sealants, potting compounds, lubricants, paints and finishes, inks, films, encapsulants, elastomers, structural plastics, ablatives, adhesives, and electrical and thermal insulation. Thermochemical data showing degradation as a function of temperature, from room to 500 C, are included.

  11. Multifunctional nanocomposite materials

    SciTech Connect

    Roy, R.; Komarneni, S.

    1991-11-01

    Objective is to examine the low temperature nanocomposite route in the synthesis of multifunctional materials using two-dimensional clays as hosts. After about 8 months, a significant advance was made in the design and synthesis of novel nanocomposite materials, which are nanometal intercalated clays prepared by a low temperature route. A layered V[sub 2]O[sub 5] gel has been made hydrothermally and its cation exchange properties measured. Several pillared clays have also been synthesized and characterized.

  12. Beam-Material Interaction

    SciTech Connect

    Mokhov, N. V.; Cerutti, F.

    2016-01-01

    Th is paper is motivated by the growing importance of better understanding of the phenomena and consequences of high-intensity energetic particle beam interactions with accelerator, generic target, and detector components. It reviews the principal physical processes of fast-particle interactions with matter, effects in materials under irradiation, materials response, related to component lifetime and performance, simulation techniques, and methods of mitigating the impact of radiation on the components and environment in challenging current and future applications.

  13. USGS reference materials

    USGS Publications Warehouse

    ,

    1995-01-01

    Every year in the United States, millions of measurements are made on the chemical composition of items that affect us on a daily basis. Determining the accuracy of these measurements is based on the analysis of appropriate reference materials whose composition was previously determined through rigorous testing. Today, reference materials help us evaluate the composition of the food we eat, medicine we use, soil we grow our crops in, and hundreds of other products that affect our everyday lives.

  14. Container for radioactive materials

    DOEpatents

    Fields, Stanley R.

    1985-01-01

    A container for housing a plurality of canister assemblies containing radioactive material and disposed in a longitudinally spaced relation within a carrier to form a payload package concentrically mounted within the container. The payload package includes a spacer for each canister assembly, said spacer comprising a base member longitudinally spacing adjacent canister assemblies from each other and a sleeve surrounding the associated canister assembly for centering the same and conducting heat from the radioactive material in a desired flow path.

  15. Noise Abatement Materials

    NASA Technical Reports Server (NTRS)

    1986-01-01

    A former NASA employee who discovered a kind of plastic that soaked up energy, dampened vibrations, and was a good noise abatement material, founded a company to market noise deadening adhesives, sheets, panels and enclosures. Known as SMART products, they are 75-80% lighter than ordinary soundproofing material and have demonstrated a high degree of effectiveness. The company, Varian Associates, makes enclosures for high voltage terminals and other electronic system components, and easily transportable audiometric test booths.

  16. Computerized material accounting

    SciTech Connect

    Claborn, J.; Erkkila, B.

    1995-07-01

    With the advent of fast, reliable database servers running on inexpensive networked personal computers, it is possible to create material accountability systems that are easy to learn, easy to use, and cost-effective to implement. Maintaining the material data in a relational database allows data to be viewed in ways that were previously very difficult. This paper describes a software and hardware platforms for the implementation of such an accountability system.

  17. Biomimetic Hydrogel Materials

    DOEpatents

    Bertozzi, Carolyn , Mukkamala, Ravindranath , Chen, Oing , Hu, Hopin , Baude, Dominique

    2003-04-22

    Novel biomimetic hydrogel materials and methods for their preparation. Hydrogels containing acrylamide-functionalized carbohydrate, sulfoxide, sulfide or sulfone copolymerized with a hydrophilic or hydrophobic copolymerizing material selected from the group consisting of an acrylamide, methacrylamide, acrylate, methacrylate, vinyl and a derivative thereof present in concentration from about 1 to about 99 wt %. and methods for their preparation. The method of use of the new hydrogels for fabrication of soft contact lenses and biomedical implants.

  18. Biomimetic hydrogel materials

    DOEpatents

    Bertozzi, Carolyn; Mukkamala, Ravindranath; Chen, Qing; Hu, Hopin; Baude, Dominique

    2000-01-01

    Novel biomimetic hydrogel materials and methods for their preparation. Hydrogels containing acrylamide-functionalized carbohydrate, sulfoxide, sulfide or sulfone copolymerized with a hydrophilic or hydrophobic copolymerizing material selected from the group consisting of an acrylamide, methacrylamide, acrylate, methacrylate, vinyl and a derivative thereof present in concentration from about 1 to about 99 wt %. and methods for their preparation. The method of use of the new hydrogels for fabrication of soft contact lenses and biomedical implants.

  19. LDEF materials data bases

    NASA Technical Reports Server (NTRS)

    Funk, Joan G.; Strickland, John W.; Davis, John M.

    1993-01-01

    The Long Duration Exposure Facility (LDEF) and the accompanying experiments were composed of and contained a wide variety of materials representing the largest collection of materials flown in low Earth orbit (LEO) and retrieved for ground based analysis to date. The results and implications of the mechanical, thermal, optical, and electrical data from these materials are the foundation on which future LEO space missions will be built. The LDEF Materials Special Investigation Group (MSIG) has been charged with establishing and developing data bases to document these materials and their performance to assure not only that the data are archived for future generations but also that the data are available to the spacecraft user community in an easily accessed, user-friendly form. This paper discusses the format and content of the three data bases developed or being developed to accomplish this task. The hardware and software requirements for each of these three data bases are discussed along with current availability of the data bases. This paper also serves as a user's guide to the MAPTIS LDEF Materials Data Base.

  20. Superconducting materials processing

    NASA Technical Reports Server (NTRS)

    Hurley, John S.; Karikari, Emmanuel K.; Hiamang, S. O.; Danjaji, M.; Bassey, Affiong; Morgan, Andre

    1995-01-01

    The effects of materials processing on the properties and behavior of high temperature yttrium barium copper oxide (YBCO) superconductors were investigated. Electrical, magnetic, and structural characteristics of thin films (300 nm) YBA2CU3O(delta) structures grown by pulsed laser deposition on LaAlO3 and SrTiO3 substrates were used to evaluate processing. Pole projection and thin film diffraction measurements were used to establish grain orientation and verify structural integrity of the samples. Susceptibility magnetization, and transport measurements were used to evaluate the magnetic and electrical transport properties of the samples. Our results verified that an unfortunate consequence of processing is inherent changes to the internal structure of the material. This effect translates into modifications in the properties of the materials, and undesired feature that makes it very difficult to consistently predict material behavior. The results show that processing evaluation must incorporate a comprehensive understanding of the properties of the materials. Future studies will emphasize microstructural characteristics of the materials, in particular, those microscopic properties that map macroscopic behavior.

  1. Nano-scale materials

    SciTech Connect

    Barrera, J.; Smith, D.C.; Devlin, D.J.

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Highly selective, alumina-supported molybdenum carbonitrides were prepared by solution impregnation using the metal amide Mo{sub 2}(N(CH{sub 3}){sub 2}){sub 6} as a molecular precursor. On the basis of relative weight percents, these materials demonstrate a 5- to 8-fold increase in catalytic activity over similar materials prepared by traditional solid-state approaches. The catalytic activities of these materials are very dependent upon the type of alumina support used. Impregnation of Mo{sub m}C{sub x}N{sub y} into preformed alumina pellets resulted in a material that specifically isomerized n-heptane into equal amounts of 2- and 3-methylhexanes, as well as iso-butane. No evidence of aromatic products was observed at operating temperatures below 420{degrees}C. The product selectivity of the isomers was 56% at a n-heptane conversion efficiency of 57%. Impregnating Mo{sub m}C{sub x}N{sub y} into an alumina powder resulted in an extremely selective aromatized and dehydrogenated material. The products from this material consist only of aromatics and n-heptenes with less than 2% isomerization or cracking products.

  2. Nuclear Material Management Abstract

    SciTech Connect

    Jesse C. Schreiber

    2007-07-10

    Nevada Test Site (NTS) has transitioned from its historical and critical role of weapons testing to another critical role for the nation. This new role focuses on being a integral element in solving the multiple challenges facing the National Nuclear Security Administration (NNSA) with nuclear material management. NTS is positioned to be a solution for other NNSA sites challenged with safe nuclear materials storage and disposition. NNSA, with site involvement, is currently transforming the nuclear stockpile and supporting infrastructure to meet the 2030 vision. Efforts are under way to consolidate and modernize the production complex . With respect to the nuclear material stockpile, the NNSA sites are currently reducing the complex nuclear material inventory through disposition and consolidation. This includes moving material from other sites to NTS. State of the art nuclear material management and control practices at NTS are essential for NTS to ensure that assigned activities are accomplished in a safe, secure, efficient, and environmentally responsible manner. NTS activities and challenges will be addressed.

  3. EDITORIAL: Materially speaking!

    NASA Astrophysics Data System (ADS)

    Cornwall, Malcolm G.

    1997-05-01

    We live in a highly materialistic age. This is true not only for our spiritual outlook - or lack of it - but undeniably so for the physical world in which we live. Materials, which are the feature of this special issue, provide literally the fabric on which the modern world is built. Materials science is the systematic study of the physical properties and behaviour of solids with practical applications and importance (if the utility of the material is not explicit or important we are probably in the realm of solid state physics!). Materials in this sense are the stuff of which cars and computers, jet aircraft and washing machines, tower blocks and saucepans, bridges and golf clubs are made. The science of materials therefore encompasses most of the things that form the infrastructure of modern life. But perhaps it is its very ubiquity that removes the mystique, the glamour, the 'zing' from the subject. In contrast, anything cosmological, astronomical or 'fundamental' (as in 'particle'), i.e. of little or no practical significance to our day-to-day lives, excites the curiosity of many able young people. Witness the profusion of books about galaxies and black holes, and quarks and GUTs which strain the popular science shelves of the bookshops. I'm probably being heretical, but perhaps the over-hyping of the very large and the very small has indeed attracted the able few into the serious study of physics, but because of its inherent mathematical complexity and esoteric remoteness maybe it has put off the average youngster who would nevertheless enjoy and succeed in physics-based higher education (and, not incidentally, help fill the seriously depleted lecture theatres in many university physics - and engineering - departments). Materials science on the other hand deals with an intermediate range of things which, give or take an order of magnitude or three, are person-sized as well as person useful. It is - therefore? - undoubtedly one of the less glamorous of the

  4. Tribological comparison of materials

    NASA Astrophysics Data System (ADS)

    Shi, Bing

    Approximately 600,000 total joint replacement surgeries are performed each year in the United States. Current artificial joint implants are mainly metal-on-plastic. The synthetic biomaterials undergo degradation through fatigue and corrosive wear from load-bearing and the aqueous ionic environment of the human body. Deposits of inorganic salts can scratch weight-bearing surfaces, making artificial joints stiff and awkward. The excessive wear debris from polyethylene leads to osteolysis and potential loosening of the prosthesis. The lifetime for well-designed artificial joints is at most 10 to 15 years. A patient can usually have two total joint replacements during her/his lifetime. Durability is limited by the body's reaction to wear debris of the artificial joints. Wear of the artificial joints should be reduced. A focus of this thesis is the tribological performance of bearing materials for Total Replacement Artificial Joints (TRAJ). An additional focus is the scaffolds for cell growth from both a tissue engineering and tribological perspective. The tribological properties of materials including Diamond-like Carbon (DLC) coated materials were tested for TRAJ implants. The DLC coatings are chemically inert, impervious to acid and saline media, and are mechanically hard. Carbon-based materials are highly biocompatible. A new alternative to total joints implantation is tissue engineering. Tissue engineering is the replacement of living tissue with tissue that is designed and constructed to meet the needs of the individual patient. Cells were cultured onto the artificial materials, including metals, ceramics, and polymers, and the frictional properties of these materials were investigated to develop a synthetic alternative to orthopedic transplants. Results showed that DLC coated materials had low friction and wear, which are desirable tribological properties for artificial joint material. Cells grew on some of the artificial matrix materials, depending on the

  5. Catalog of Martian Materials

    NASA Astrophysics Data System (ADS)

    Newsom, Horton E.; Hagerty, J. J.

    1998-01-01

    The long-term exploration of Mars will require the utilization of surface and near-surface materials for construction, radiation shielding, and life support. Eventually, such materials could be used as raw materials in manufacturing. While there is a resemblance between the surface of Mars, as revealed in Viking and Pathfinder images, and terrestrial desert environments, there are distinct differences that will affect the utilization of in situ resources. In general, the surface geological features are extremely old compared to Earth, dating back to the early evolution of the solar system. Therefore, materials created by processes such as impact cratering are important on Mars. Impact cratering probably created extensive sheets of impact melt bearing breccias on the surface and resulted in the formation of a thick regolith of broken rock fragments in the ancient terrains of Mars. Another key feature is the lack of rainfall over most of Mars' history. This resulted in the lack of extensive erosion. On Earth, extensive erosion of volcanic centers, for example, has exposed deep hydrothermal deposits that are mined for Cu, Mo, and W, but such deposits are not likely to be exposed at the surface on Mars. Similarly, deposits of quartz sand, used for glass making, are created by the erosion of granitic terrains on Earth, and are not likely to be found on Mars. The soil on Mars is also very different from wind-blown material on Earth. Virtually no organic material is present, and the material is enriched in volatile elements, such as S and Cl, and possibly also toxic heavy metals, derived from volcanic gases and hydrothermal waters that poured onto the surface. The volatile elements have remained in the soil due to the absence of processes that recycle volatile elements back into the planet's crust. Hydrogen peroxide originally formed in the atmosphere is also mixed into the soil and regolith, and was probably responsible for the "oxidant" found in the soil by the Viking

  6. Thermodynamics of Thermoelectric Materials

    NASA Astrophysics Data System (ADS)

    Doak, Jeff W.

    One challenge facing society is the responsible use of our energy resources. Increasing the efficiency of energy generation provides one path to solving this challenge. One commonality among most current energy generation methods is that waste heat is generated during the generation process. Thermoelectrics can provide a solution to increasing the efficiency of power generation and automotive systems by converting waste heat directly to electricity. The current barrier to implementation of thermoelectric systems is the low efficiencies of underlying thermoelectric materials. The efficiency of a thermoelectric material depends on the electronic and thermal transport properties of the material; a good thermoelectric material should be an electronic conductor and a thermal insulator, traits which generally oppose one another. The thermal properties of a thermoelectric material can be improved by forming nanoscale precipitates with the material which scatter phonons, reducing the thermal conductivity. The electronic properties of a thermoelectric material can be improved by doping the material to increase the electronic conductivity or by alloying the material to favorably alter its band structure. The ability of these chemical modifications to affect the thermoelectric efficiency of material are ultimately governed by the chemical thermodynamics of the system. PbTe is a prototypical thermoelectric material: Alloying PbTe with PbS (or other materials) creates nanostructures which scatter phonons and reduce the lattice thermal conductivity. Doping PbTe with Na increases the hole concentration, increasing the electronic conductivity. In this work, we investigate the thermodynamics of PbTe and similar systems using first principles to understand the underlying mechanisms controlling the formation of nanostructures and the amount of doping allowed in these systems. In this work we: 1) investigate the thermodynamics of pseudo-binary alloys of IV--VI systems to identify the

  7. Microwave impregnation of porous materials with thermal energy storage materials

    DOEpatents

    Benson, David K.; Burrows, Richard W.

    1993-01-01

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  8. Microwave impregnation of porous materials with thermal energy storage materials

    DOEpatents

    Benson, D.K.; Burrows, R.W.

    1993-04-13

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  9. Microwave impregnation of porous materials with thermal energy storage materials

    SciTech Connect

    Benson, D.K.; Burrows, R.W.

    1991-03-13

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent tc the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  10. Microwave impregnation of porous materials with thermal energy storage materials

    SciTech Connect

    Benson, D.K.; Burrows, R.W.

    1992-12-31

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  11. ATS materials support

    SciTech Connect

    Karnitz, M.A.; Wright, I.G.; Ferber, M.K.; Holcomb, R.S.; Rawlins, M.H.

    1996-12-31

    The technology based portion of the Advanced Turbine System Program (ATS) contains several subelements which address generic technology issues for land-base gas turbine systems. One subelement is the Materials/Manufacturing Technology Program which is coordinated by DOE-Oak Ridge Operations and Oak Ridge National laboratory (ORNL) for the Department of Energy. The work in this subelement is being performed predominantly by industry with assistance from national laboratories and universities. Projects in this subelement are aimed toward hastening the incorporation of new materials and components in gas turbines. The materials manufacturing subelement was developed with input from gas turbine manufacturers, material suppliers, government laboratories and universities. Work is currently ongoing on thermal barrier coatings (TBCs), the scale-up of single-crystal airfoil manufacturing technologies, materials characterization and technology information exchange. Westinghouse Power Generation and Pratt and Whitney each have material programs to develop dependable TBCs that enable increased turbine inlet temperatures while maintaining airfoil substrate temperatures at levels to meet the ATS life goals. Howmet and PCC Airfoils each have projects to extend the capability of single-crystal complex-cored airfoil technology to larger sizes so that higher turbine inlet temperatures can be attained in land-based turbines in a cost-effective manner. Materials characterization tasks are ongoing on TBCs in support of the industrial projects. In addition, a project on long-term testing of ceramics and ceramic-matrix composites for gas turbines is being conducted in support of programs at Solar Turbines, Allison Engines, and Westinghouse Power Generation.

  12. BUILDING MATERIALS RECLAMATION PROGRAM

    SciTech Connect

    David C. Weggel; Shen-En Chen; Helene Hilger; Fabien Besnard; Tara Cavalline; Brett Tempest; Adam Alvey; Madeleine Grimmer; Rebecca Turner

    2010-08-31

    This report describes work conducted on the Building Materials Reclamation Program for the period of September 2008 to August 2010. The goals of the project included selecting materials from the local construction and demolition (C&D) waste stream and developing economically viable reprocessing, reuse or recycling schemes to divert them from landfill storage. Educational resources as well as conceptual designs and engineering feasibility demonstrations were provided for various aspects of the work. The project was divided into two distinct phases: Research and Engineering Feasibility and Dissemination. In the Research Phase, a literature review was initiated and data collection commenced, an advisory panel was organized, and research was conducted to evaluate high volume C&D materials for nontraditional use; five materials were selected for more detailed investigations. In the Engineering Feasibility and Dissemination Phase, a conceptual study for a regional (Mecklenburg and surrounding counties) collection and sorting facility was performed, an engineering feasibility project to demonstrate the viability of recycling or reuse schemes was created, the literature review was extended and completed, and pedagogical materials were developed. Over the two-year duration of the project, all of the tasks and subtasks outlined in the original project proposal have been completed. The Final Progress Report, which briefly describes actual project accomplishments versus the tasks/subtasks of the original project proposal, is included in Appendix A of this report. This report describes the scientific/technical aspects (hypotheses, research/testing, and findings) of six subprojects that investigated five common C&D materials. Table 1 summarizes the six subprojects, including the C&D material studied and the graduate student and the faculty advisor on each subproject.

  13. [Elastomeric impression materials].

    PubMed

    Levartovsky, S; Folkman, M; Alter, E; Pilo, R

    2011-04-01

    Elastomeric impression materials are in common use. The impression taken should be highly precise, thus, requiring specific care when manipulatingthese materials. There are 4 groups of elastomers; polysulfide, condensation silicone, addition silicone and polyether; each differ in their setting mechanism and their physical and chemical properties. This review elaborates the major properties of elastomers and its implications on their use. The impression material is inserted into the patient's mouth in a viscous state and transforms into viscoelastic state, upon withdrawal, influencing the residual deformation. The requirements are minimal residual deformation or maximal elastic recovery. As the mouth is a wet environment a major consideration is hydrophilicity. The wettability which is estimated by measuring either the contact angle of a droplet of water and the substrate post setting or the contact angle of a droplet of impression material and the wet tooth pre setting, determines the interaction of the material with both mouth fluids and gypsum. As the primary end target is to obtain a model depicting accurately the oral details, an attention to the impressions' compatibility with gypsum should also be given. Many studies were conducted to get a thorough understanding of the hydrophilic properties of each material, and the mechanism utilized, such as surfactants in hydrophilic PVS. Polyether is the only material that is truly hydrophilic; it exhibits the lowest contact angle, during and after setting. Recent studies show that during setting the Polyether hydrophilicity is increased compared to the condition after setting. Dimensional stability, a crucial property of the impression, is affected by the physical and chemical attributes of the material, such as its tear strength. Polysulfide has the highest tear strength. Tear Strength is affected by two major parameters, viscosity, a built-in property, and how fast the impression is pulled out of the mouth, the

  14. Nanostructured materials in potentiometry.

    PubMed

    Düzgün, Ali; Zelada-Guillén, Gustavo A; Crespo, Gastón A; Macho, Santiago; Riu, Jordi; Rius, F Xavier

    2011-01-01

    Potentiometry is a very simple electrochemical technique with extraordinary analytical capabilities. It is also well known that nanostructured materials display properties which they do not show in the bulk phase. The combination of the two fields of potentiometry and nanomaterials is therefore a promising area of research and development. In this report, we explain the fundamentals of potentiometric devices that incorporate nanostructured materials and we highlight the advantages and drawbacks of combining nanomaterials and potentiometry. The paper provides an overview of the role of nanostructured materials in the two commonest potentiometric sensors: field-effect transistors and ion-selective electrodes. Additionally, we provide a few recent examples of new potentiometric sensors that are based on receptors immobilized directly onto the nanostructured material surface. Moreover, we summarize the use of potentiometry to analyze processes involving nanostructured materials and the prospects that the use of nanopores offer to potentiometry. Finally, we discuss several difficulties that currently hinder developments in the field and some future trends that will extend potentiometry into new analytical areas such as biology and medicine.

  15. New microwave coupler material

    SciTech Connect

    Holcombe, C.E.

    1983-12-01

    The unexpected coupling of urania (UO/sub x/, with 2 less than or equal to x less than or equal to 3) to microwave energy has previously been reported. The present study screened several different materials for coupling with microwave energy using a 1.6 kW, 2450 MHz system. Materials were nominally -100 mesh powder, >99% pure. Those which showed minimal or no heating with the microwave energy included Y/sub 2/O/sub 3/, Al/sub 2/O/sub 3/, SiO/sub 2/, BN, graphite, and unstabilized ZrO/sub 2/. Pronounced heating occurred with B/sub 4/C. This discovery led to the following evaluation/comparison of the coupling ability of B/sub 4/C with water, structurally similar materials (boron suboxide, B/sub 6/O - prepared from zinc oxide and boron, microcrystalline or amorphous boron, ..cap alpha..-type), and UO/sub 2/. In order to compare relative heating rates, the materials were placed into 50 mL beakers, covered with alumina-silica felt insulation, and subjected to 30 s at full power (both top and bottom sources on). The temperature was measured at the end of the test, after the door automatically opened, by inserting a type K thermocouple into the material. For the powders, the thermocouple was moved about to obtain the highest reading, although only a 10% or so variation occurred before the temperature dropped from heat losses. 4 references, 1 table.

  16. Material bagging device

    DOEpatents

    Wach, Charles G.; Nelson, Robert E.; Brak, Stephen B.

    1984-01-01

    A bagging device for transferring material from one chamber through an opening in a wall to a second chamber includes a cylindrical housing communicating with the opening and defining a passage between the chambers. A cylindrical cartridge is slidably received within the housing. The cartridge has a substantially rigid cylindrical sleeve to which is affixed a pliable tube. The pliable tube is positioned concentrically about the sleeve and has a pleated portion capable of unfolding from the sleeve and a closed end extending over a terminal end of the sleeve. Sealing means are interposed in sealed relationship between the cartridge and the housing. Material from one chamber is inserted into the cartridge secured in the housing and received in the closed end of the tube which unfolds into the other chamber enclosing the material therein. The tube may then be sealed behind the material and then severed to form a bag-like enclosure defined by the tube's closed terminal end and the new seal. The new seal then forms a terminal end for the unsevered portion of the pliable tube into which additional material may be placed and the bagging process repeated.

  17. Astrophysics with Extraterrestrial Materials

    NASA Astrophysics Data System (ADS)

    Nittler, Larry R.; Ciesla, Fred

    2016-09-01

    Extraterrestrial materials, including meteorites, interplanetary dust, and spacecraft-returned asteroidal and cometary samples, provide a record of the starting materials and early evolution of the Solar System. We review how laboratory analyses of these materials provide unique information, complementary to astronomical observations, about a wide variety of stellar, interstellar and protoplanetary processes. Presolar stardust grains retain the isotopic compositions of their stellar sources, mainly asymptotic giant branch stars and Type II supernovae. They serve as direct probes of nucleosynthetic and dust formation processes in stars, galactic chemical evolution, and interstellar dust processing. Extinct radioactivities suggest that the Sun's birth environment was decoupled from average galactic nucleosynthesis for some tens to hundreds of Myr but was enriched in short-lived isotopes from massive stellar winds or explosions shortly before or during formation of the Solar System. Radiometric dating of meteorite components tells us about the timing and duration over which solar nebula solids were assembled into the building blocks of the planets. Components of the most primitive meteoritical materials provide further detailed constraints on the formation, processing, and transport of material and associated timescales in the Sun's protoplanetary disk as well as in other forming planetary systems.

  18. Panel 3 - material science

    SciTech Connect

    Sarrao, John L; Yip, Sidney

    2010-01-01

    In the last decades, NNSA's national security challenge has evolved, and the role of simulation and computation has grown dramatically. The process of certifying nuclear weapons performance has changed from one based on integrated tests to science-based certification in which underground nuclear tests have been replaced by large-scale simulations, appropriately validated with fundamental experimental data. Further, the breadth of national security challenges has expanded beyond stewardship of a nuclear deterrent to a broad range of global and asymmetric threats. Materials challenges are central to the full suite of these national security challenges. Mission requirements demand that materials perform predictably in extreme environments -- high pressure, high strain rate, and hostile irradiation and chemical conditions. Considerable advances have been made in incorporating fundamental materials physics into integrated codes used for component certification. On the other hand, significant uncertainties still remain, and materials properties, especially at the mesoscale, are key to understanding uncertainties that remain in integrated weapons performance codes and that at present are treated as empirical knobs. Further, additional national security mission challenges could be addressed more robustly with new and higher performing materials.

  19. A Material Conferring Hemocompatibility

    PubMed Central

    Everett, William; Scurr, David J; Rammou, Anna; Darbyshire, Arnold; Hamilton, George; de Mel, Achala

    2016-01-01

    There is a need for biomimetic materials for use in blood-contacting devices. Blood contacting surfaces maintain their patency through physico-chemical properties of a functional endothelium. A poly(carbonate-urea) urethane (PCU) is used as a base material to examine the feasibility of L-Arginine methyl ester (L-AME) functionalized material for use in implants and coatings. The study hypothesizes that L-AME, incorporated into PCU, functions as a bioactive porogen, releasing upon contact with blood to interact with endothelial nitric oxide synthase (eNOS) present in blood. Endothelial progenitor cells (EPC) were successfully cultured on L-AME functionalized material, indicating that L-AME -increases cell viability. L-AME functionalized material potentially has broad applications in blood-contacting medical devices, as well as various other applications requiring endogenous up-regulation of nitric oxide, such as wound healing. This study presents an in-vitro investigation to demonstrate the novel anti-thrombogenic properties of L-AME, when in solution and when present within a polyurethane-based polymer. PMID:27264087

  20. Dynamic Strength of Materials

    NASA Astrophysics Data System (ADS)

    Chhabildas, Lalit

    2011-06-01

    Historically when shock loading techniques became accessible in the early fifties it was assumed that materials behave like fluids implying that materials cannot support any shear stresses. Early and careful investigation in the sixties by G. R. Fowles in aluminum indicated otherwise. When he compared his Hugoniot compression measurements to hydrostatic pressure compression measurements in the pressure volume plane he noticed that the shock data lay above the hydrostatic compression curve - which laid the ground work for what is the basis for elastic-plastic theories that exist today. In this talk, a brief historical perspective on strength measurements in materials will be discussed including how time-resolved techniques have played a role in allowing estimates of the strength of materials at over Mbar stress. This is crucial especially at high stresses since we are determining values that are small compared to the loading stress. Even though we have made considerable progress in our understanding of materials, there are still many anomalies and unanswered questions. Some of these anomalies are fertile grounds for further and future research and will be mentioned.