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Sample records for ageing model podospora

  1. A genome-wide longitudinal transcriptome analysis of the aging model Podospora anserina.

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    Oliver Philipp

    Full Text Available Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression. A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii present testable predictions for subsequent experimental investigations.

  2. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina

    DEFF Research Database (Denmark)

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis

    2009-01-01

    The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA ...

  3. The genome sequence of the model ascomycete fungus Podospora anserina

    NARCIS (Netherlands)

    Espagne, Eric; Lespinet, Olivier; Malagnac, Fabienne; Da Silva, Corinne; Jaillon, Olivier; Porcel, Betina M; Couloux, Arnaud; Aury, Jean-Marc; Ségurens, Béatrice; Poulain, Julie; Anthouard, Véronique; Grossetete, Sandrine; Khalili, Hamid; Coppin, Evelyne; Déquard-Chablat, Michelle; Picard, Marguerite; Contamine, Véronique; Arnaise, Sylvie; Bourdais, Anne; Berteaux-Lecellier, Véronique; Gautheret, Daniel; de Vries, Ronald P; Battaglia, Evy; Coutinho, Pedro M; Danchin, Etienne Gj; Henrissat, Bernard; Khoury, Riyad El; Sainsard-Chanet, Annie; Boivin, Antoine; Pinan-Lucarré, Bérangère; Sellem, Carole H; Debuchy, Robert; Wincker, Patrick; Weissenbach, Jean; Silar, Philippe

    2008-01-01

    BACKGROUND: The dung-inhabiting ascomycete fungus Podospora anserina is a model used to study various aspects of eukaryotic and fungal biology, such as ageing, prions and sexual development. RESULTS: We present a 10X draft sequence of P. anserina genome, linked to the sequences of a large expressed

  4. Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina

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    Matthias Wiemer

    2014-06-01

    Full Text Available Aging of biological systems is influenced by various factors, conditions and processes. Among others, processes allowing organisms to deal with various types of stress are of key importance. In particular, oxidative stress as the result of the generation of reactive oxygen species (ROS at the mitochondrial respiratory chain and the accumulation of ROS-induced molecular damage has been strongly linked to aging. Here we view the impact of ROS from a different angle: their role in the control of gene expression. We report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina grown on medium containing paraquat (PQ. This treatment leads to an increased cellular generation and release of H2O2, a reduced growth rate, and a decrease in lifespan. The combined challenge by PQ and copper has a synergistic negative effect on growth and lifespan. The data from the transcriptome analysis of the wild type cultivated under PQ-stress and their comparison to those of a longitudinal aging study as well as of a copper-uptake longevity mutant of P. anserina revealed that PQ-stress leads to the up-regulation of transcripts coding for components involved in mitochondrial remodeling. PQ also affects the expression of copper-regulated genes suggesting an increase of cytoplasmic copper levels as it has been demonstrated earlier to occur during aging of P. anserina and during senescence of human fibroblasts. This effect may result from the induction of the mitochondrial permeability transition pore via PQ-induced ROS, leading to programmed cell death as part of an evolutionary conserved mechanism involved in biological aging and lifespan control.

  5. Genomic conflicts in Podospora anserina = Genomische conflicten in Podospora anserina

    NARCIS (Netherlands)

    Gaag, van der M.

    2005-01-01

    This thesis deals with genomic conflicts raised by selfish elements in the ascomycete fungus Podospora anserina .Genomic conflicts arise when the effects of the selfish elements are opposite to the interests of the other parts of the geno

  6. Genetic control of anastomosis in Podospora anserina.

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    Tong, Laetitia Chan Ho; Silar, Philippe; Lalucque, Hervé

    2014-09-01

    We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.

  7. A mutation in the gene encoding cytochrome c1 leads to a decreased ROS content and to a long-lived phenotype in the filamentous fungus Podospora anserina.

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    Sellem, Carole H; Marsy, Sophie; Boivin, Antoine; Lemaire, Claire; Sainsard-Chanet, Annie

    2007-07-01

    We present here the properties of a complex III loss-of-function mutant of the filamentous fungus Podospora anserina. The mutation corresponds to a single substitution in the second intron of the gene cyc1 encoding cytochrome c(1), leading to a splicing defect. The cyc1-1 mutant is long-lived, exhibits a defect in ascospore pigmentation, has a reduced growth rate and a reduced ROS production associated with a stabilisation of its mitochondrial DNA. We also show that increased longevity is linked with morphologically modified mitochondria and an increased number of mitochondrial genomes. Overexpression of the alternative oxidase rescues all these phenotypes and restores aging. Interestingly, the absence of complex III in this mutant is not paralleled with a deficiency in complex I activity as reported in mammals although the respiratory chain of P. anserina has recently been demonstrated to be organized according to the "respirasome" model.

  8. Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide.

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    Grimm, Carolin; Osiewacz, Heinz D

    2015-03-01

    For biological systems, balancing cellular levels of reactive oxygen species (ROS) is of great importance because ROS are both, essential for cellular signaling and dangerous in causing molecular damage. Cellular ROS abundance is controlled by a delicate network of molecular pathways. Within this network, superoxide dismutases (SODs) are active in disproportion of the superoxide anion leading to the formation of hydrogen peroxide. The fungal aging model Podospora anserina encodes at least three SODs. One of these is the mitochondrial PaSOD3 isoform containing manganese as a cofactor. Previous work resulted in the selection of strains in which PaSod3 is strongly overexpressed. These strains display impairments in growth and lifespan. A computational model suggests a series of events to occur in Sod3 overexpressing strains leading to adverse effects due to elevated hydrogen peroxide levels. In an attempt to validate this model and to obtain more detailed information about the cellular responses involved in ROS balancing, we further investigated the PaSod3 overexpressing strains. Here we show that hydrogen peroxide levels are indeed strongly increased in the mutant strain. Surprisingly, this phenotype can be rescued by the addition of manganese to the growth medium. Strikingly, while we obtained no evidence for an antioxidant effect of manganese, we found that the metal is required for induction of components of the ROS scavenging network and lowers the hydrogen peroxide level of the mutant. A similar effect of manganese on lifespan reversion was obtained in wild-type strains challenged with exogenous hydrogen peroxide. It appears that manganese is limited under high hydrogen peroxide and suggests that a manganese-dependent activity leads to the induction of ROS scavenging components.

  9. Supramolecular organization of cytochrome c oxidase- and alternative oxidase-dependent respiratory chains in the filamentous fungus Podospora anserina.

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    Krause, Frank; Scheckhuber, Christian Q; Werner, Alexandra; Rexroth, Sascha; Reifschneider, Nicole H; Dencher, Norbert A; Osiewacz, Heinz D

    2004-06-18

    To elucidate the molecular basis of the link between respiration and longevity, we have studied the organization of the respiratory chain of a wild-type strain and of two long-lived mutants of the filamentous fungus Podospora anserina. This established aging model is able to respire by either the standard or the alternative pathway. In the latter pathway, electrons are directly transferred from ubiquinol to the alternative oxidase and thus bypass complexes III and IV. We show that the cytochrome c oxidase pathway is organized according to the mammalian "respirasome" model (Schägger, H., and Pfeiffer, K. (2000) EMBO J. 19, 1777-1783). In contrast, the alternative pathway is composed of distinct supercomplexes of complexes I and III (i.e. I(2) and I(2)III(2)), which have not been described so far. Enzymatic analysis reveals distinct functional properties of complexes I and III belonging to either cytochrome c oxidase- or alternative oxidase-dependent pathways. By a gentle colorless-native PAGE, almost all of the ATP synthases from mitochondria respiring by either pathway were preserved in the dimeric state. Our data are of significance for the understanding of both respiratory pathways as well as lifespan control and aging.

  10. Plant biomass degrading ability of the coprophilic ascomycete fungus Podospora anserina.

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    Couturier, Marie; Tangthirasunun, Narumon; Ning, Xie; Brun, Sylvain; Gautier, Valérie; Bennati-Granier, Chloé; Silar, Philippe; Berrin, Jean-Guy

    2016-01-01

    The degradation of plant biomass is a major challenge towards the production of bio-based compounds and materials. As key lignocellulolytic enzyme producers, filamentous fungi represent a promising reservoir to tackle this challenge. Among them, the coprophilous ascomycete Podospora anserina has been used as a model organism to study various biological mechanisms because its genetics are well understood and controlled. In 2008, the sequencing of its genome revealed a great diversity of enzymes targeting plant carbohydrates and lignin. Since then, a large array of lignocellulose-acting enzymes has been characterized and genetic analyses have enabled the understanding of P. anserina metabolism and development on plant biomass. Overall, these research efforts shed light on P. anserina strategy to unlock recalcitrant lignocellulose deconstruction.

  11. Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

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    Haedens, Vicki; Malagnac, Fabienne; Silar, Philippe

    2005-06-01

    Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

  12. Mitochondrial recombination increases with age in Podospora anserina

    NARCIS (Netherlands)

    van Diepeningen, Anne D; Goedbloed, Daniël J; Slakhorst, S Marijke; Koopmanschap, A Bertha; Maas, Marc F P M; Hoekstra, Rolf F; Debets, Alfons J M

    2010-01-01

    With uniparental inheritance of mitochondria, there seems little reason for homologous recombination in mitochondria, but the machinery for mitochondrial recombination is quite well-conserved in many eukaryote species. In fungi and yeasts heteroplasmons may be formed when strains fuse and transfer o

  13. Grafting as a method for studying development in the filamentous fungus Podospora anserina.

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    Silar, Philippe

    2011-08-01

    While grafting and transplant experiments have extensively been used to study development in animals and plants, they have seldom been employed to study fungal development. Here, grafting is used to study the interplay between mycelium and multicellular fruiting bodies during maturation in the model ascomycete Podospora anserina. Data indicate that grafts need a competent mycelium to continue their ripening. Vegetative incompatibility does not prevent transplanted fructifications to undergo development. Grafting onto mutant mycelia confirmed a previous model stating that the NADPH oxidase PaNox1 is required in the developing fruiting bodies, while the MAP kinase cascade PaMpk1 is required in the mycelium. Data also show that the IDC1 protein is required not only in the developing fruiting bodies but also in the mycelium, likely because of its role in anastomosis. Finally, entry inside the grafted fruiting bodies of a ribosomal protein tagged with GFP could be detected, suggesting that cellular components are imported from the underlying mycelium during maturation.

  14. Spore-killing meiotic drive factors in a natural population of the fungus Podospora anserina

    NARCIS (Netherlands)

    Gaag, van der M.; Debets, A.J.M.; Oosterhof, J.; Slakhorst, S.M.; Thijssen, J.A.G.M.; Hoekstra, R.F.

    2000-01-01

    In fungi, meiotic drive is observed as spore killing. In the secondarily homothallic ascomycete Podospora anserina it is characterized by the abortion of two of the four spores in the ascus. We have identified seven different types of meiotic drive elements (Spore killers). Among 99 isolates from na

  15. Sexual transmission of the [Het-s] prion leads to meiotic drive in Podospora anserina

    NARCIS (Netherlands)

    Dalstra, H.J.P.; Swart, K.; Debets, A.J.M.; Saupe, S.J.; Hoekstra, R.F.

    2003-01-01

    In the filamentous fungus Podospora anserina, two phenomena are associated with polymorphism at the het-s locus, vegetative incompatibility and ascospore abortion. Two het-s alleles occur naturally, het-s and het-S. The het-s encoded protein is a prion propagating as a self-perpetuating amyloid aggr

  16. The PaAlr1 magnesium transporter is required for ascospore development in Podospora anserina.

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    Grognet, Pierre; Lalucque, Hervé; Silar, Philippe

    2012-10-01

    The PaAlr1 gene encoding a putative plasma membrane magnesium (Mg) transporter in Podospora anserina was inactivated. The PaAlr1(Δ) mutants showed sensitivity to deprivation and excess Mg(2+) and Ca(2+). They also exhibited an autonomous ascospore maturation defect. Mutant ascospores were arrested at an early stage when they contained two nuclei. These data emphasize the role of Mg ions during sexual development in a filamentous fungus.

  17. Functions and regulation of the Nox family in the filamentous fungus Podospora anserina: a new role in cellulose degradation.

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    Brun, Sylvain; Malagnac, Fabienne; Bidard, Frédérique; Lalucque, Hervé; Silar, Philippe

    2009-10-01

    NADPH oxidases are enzymes that produce reactive oxygen species. Studies in mammals, plants and fungi have shown that they play important roles in differentiation, defence, host/pathogen interaction and mutualistic symbiosis. In this paper, we have identified a Podospora anserina mutant strain impaired for processes controlled by PaNox1 and PaNox2, the two Nox isoforms characterized in this model ascomycete. We show that the gene mutated is PaNoxR, the homologue of the gene encoding the regulatory subunit p67(phox), conserved in mammals and fungi, and that PaNoxR regulates both PaNox1 and PaNox2. Genome sequence analysis of P. anserina reveals that this fungus posses a third Nox isoform, PaNox3, related to human Nox5/Duox and plant Rboh. We have generated a knock-out mutant of PaNox3 and report that PaNox3 plays a minor role in P. anserina, if any. We show that PaNox1 and PaNox2 play antagonist roles in cellulose degradation. Finally, we report for the first time that a saprobic fungus, P. anserina, develops special cell structures dedicated to breach and to exploit a solid cellulosic substrate, cellophane. Importantly, as for similar structures present in some plant pathogens, their proper differentiation requires PaNox1, PaNox2, PaNoxR and the tetraspanin PaPls1.

  18. Modeled ground water age distributions

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    Woolfenden, Linda R.; Ginn, Timothy R.

    2009-01-01

    The age of ground water in any given sample is a distributed quantity representing distributed provenance (in space and time) of the water. Conventional analysis of tracers such as unstable isotopes or anthropogenic chemical species gives discrete or binary measures of the presence of water of a given age. Modeled ground water age distributions provide a continuous measure of contributions from different recharge sources to aquifers. A numerical solution of the ground water age equation of Ginn (1999) was tested both on a hypothetical simplified one-dimensional flow system and under real world conditions. Results from these simulations yield the first continuous distributions of ground water age using this model. Complete age distributions as a function of one and two space dimensions were obtained from both numerical experiments. Simulations in the test problem produced mean ages that were consistent with the expected value at the end of the model domain for all dispersivity values tested, although the mean ages for the two highest dispersivity values deviated slightly from the expected value. Mean ages in the dispersionless case also were consistent with the expected mean ages throughout the physical model domain. Simulations under real world conditions for three dispersivity values resulted in decreasing mean age with increasing dispersivity. This likely is a consequence of an edge effect. However, simulations for all three dispersivity values tested were mass balanced and stable demonstrating that the solution of the ground water age equation can provide estimates of water mass density distributions over age under real world conditions.

  19. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    NARCIS (Netherlands)

    Diepeningen, van A.D.; Debets, A.J.M.; Slakhorst-Wandel, S.M.; Hoekstra, R.F.

    2008-01-01

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with t

  20. Integration of a pAL2-1 homologous mitochondrial plasmid associated with life span extension in Podospora anserina

    NARCIS (Netherlands)

    Maas, M.F.P.M.; Sellem, C.H.; Rincheval, V.; Hoekstra, R.F.; Debets, A.J.M.; Sainsard-Chanet, A.

    2007-01-01

    We isolated and characterized a novel spontaneous longevity mutant of Podospora anserina strain Wa32 carrying one of the pAL2-1 homologous mitochondrial plasmids. This mutant is at least ten fold longer-lived than the wild type, and is hence a formal suppressor of both the regular and the `plasmid-b

  1. A non-Mendelian MAPK-generated hereditary unit controlled by a second MAPK pathway in Podospora anserina.

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    Lalucque, Hervé; Malagnac, Fabienne; Brun, Sylvain; Kicka, Sébastien; Silar, Philippe

    2012-06-01

    The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.

  2. In vivo labelling of functional ribosomes reveals spatial regulation during starvation in Podospora anserina

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    Silar Philippe

    2000-11-01

    Full Text Available Abstract Background To date, in eukaryotes, ribosomal protein expression is known to be regulated at the transcriptional and/or translational levels. But other forms of regulation may be possible. Results Here, we report the successful tagging of functional ribosomal particles with a S7-GFP chimaeric protein, making it possible to observe in vivo ribosome dynamics in the filamentous fungus Podospora anserina. Microscopic observations revealed a novel kind of ribosomal protein regulation during the passage between cell growth and stationary phases, with a transient accumulation of ribosomal proteins and/or ribosome subunits in the nucleus, possibly the nucleolus, being observed at the beginning of stationary phase. Conclusion Nuclear sequestration can be another level of ribosomal protein regulation in eukaryotic cells.This may contribute to the regulation of cell growth and division.

  3. Larvicidal activity of metabolites from the endophytic Podospora sp. against the malaria vector Anopheles gambiae.

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    Matasyoh, Josphat C; Dittrich, Birger; Schueffler, Anja; Laatsch, Hartmut

    2011-03-01

    In a screening for natural products with mosquito larvicidal activities, the endophytic fungus Podospora sp. isolated from the plant Laggera alata (Asteraceae) was conspicuous. Two xanthones, sterigmatocystin (1) and secosterigmatocystin (2), and an anthraquinone derivative (3) 13-hydroxyversicolorin B were isolated after fermentation on M(2) medium. These compounds were characterised using spectroscopic and X-ray analysis and examined against third instar larvae of Anopheles gambiae. The results demonstrated that compound 1 was the most potent one with LC(50) and LC(90) values of 13.3 and 73.5 ppm, respectively. Over 95% mortality was observed at a concentration 100 ppm after 24 h. These results compared farvorably with the commercial larvicide pylarvex® that showed 100% mortality at the same concentration. Compound 3 was less potent and had an LC(50) of 294.5 ppm and over 95% mortality was achieved at a concentration of 1,000 ppm. Secosterigmatocystin (2) revealed relatively weak activity and therefore LC values were not determined.

  4. Identification of a Hypothetical Protein from Podospora anserina as a Nitroalkane Oxidase

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    Tormos, Jose R.; Taylor, Alexander B.; Daubner, S. Colette; Hart, P. John; Fitzpatrick, Paul F. (Texas-HSC); (St. Mary)

    2010-08-23

    The flavoprotein nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of primary and secondary nitroalkanes to their respective aldehydes and ketones. Structurally, the enzyme is a member of the acyl-CoA dehydrogenase superfamily. To date no enzymes other than that from F. oxysporum have been annotated as NAOs. To identify additional potential NAOs, the available database was searched for enzymes in which the active site residues Asp402, Arg409, and Ser276 were conserved. Of the several fungal enzymes identified in this fashion, PODANSg2158 from Podospora anserina was selected for expression and characterization. The recombinant enzyme is a flavoprotein with activity on nitroalkanes comparable to the F. oxysporum NAO, although the substrate specificity is somewhat different. Asp399, Arg406, and Ser273 in PODANSg2158 correspond to the active site triad in F. oxysporum NAO. The k{sub cat}/K{sub M}-pH profile with nitroethane shows a pK{sub a} of 5.9 that is assigned to Asp399 as the active site base. Mutation of Asp399 to asparagine decreases the k{sub cat}/K{sub M} value for nitroethane over 2 orders of magnitude. The R406K and S373A mutations decrease this kinetic parameter by 64- and 3-fold, respectively. The structure of PODANSg2158 has been determined at a resolution of 2.0 {angstrom}, confirming its identification as an NAO.

  5. Wood utilization is dependent on catalase activities in the filamentous fungus Podospora anserina.

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    Bourdais, Anne; Bidard, Frederique; Zickler, Denise; Berteaux-Lecellier, Veronique; Silar, Philippe; Espagne, Eric

    2012-01-01

    Catalases are enzymes that play critical roles in protecting cells against the toxic effects of hydrogen peroxide. They are implicated in various physiological and pathological conditions but some of their functions remain unclear. In order to decipher the role(s) of catalases during the life cycle of Podospora anserina, we analyzed the role of the four monofunctional catalases and one bifunctional catalase-peroxidase genes present in its genome. The five genes were deleted and the phenotypes of each single and all multiple mutants were investigated. Intriguingly, although the genes are differently expressed during the life cycle, catalase activity is dispensable during both vegetative growth and sexual reproduction in laboratory conditions. Catalases are also not essential for cellulose or fatty acid assimilation. In contrast, they are strictly required for efficient utilization of more complex biomass like wood shavings by allowing growth in the presence of lignin. The secreted CATB and cytosolic CAT2 are the major catalases implicated in peroxide resistance, while CAT2 is the major player during complex biomass assimilation. Our results suggest that P. anserina produces external H(2)O(2) to assimilate complex biomass and that catalases are necessary to protect the cells during this process. In addition, the phenotypes of strains lacking only one catalase gene suggest that a decrease of catalase activity improves the capacity of the fungus to degrade complex biomass.

  6. Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.

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    Evelyne Coppin

    Full Text Available Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.

  7. Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.

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    Coppin, Evelyne; Berteaux-Lecellier, Véronique; Bidard, Frédérique; Brun, Sylvain; Ruprich-Robert, Gwenaël; Espagne, Eric; Aït-Benkhali, Jinane; Goarin, Anne; Nesseir, Audrey; Planamente, Sara; Debuchy, Robert; Silar, Philippe

    2012-01-01

    Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.

  8. Wood utilization is dependent on catalase activities in the filamentous fungus Podospora anserina.

    Directory of Open Access Journals (Sweden)

    Anne Bourdais

    Full Text Available Catalases are enzymes that play critical roles in protecting cells against the toxic effects of hydrogen peroxide. They are implicated in various physiological and pathological conditions but some of their functions remain unclear. In order to decipher the role(s of catalases during the life cycle of Podospora anserina, we analyzed the role of the four monofunctional catalases and one bifunctional catalase-peroxidase genes present in its genome. The five genes were deleted and the phenotypes of each single and all multiple mutants were investigated. Intriguingly, although the genes are differently expressed during the life cycle, catalase activity is dispensable during both vegetative growth and sexual reproduction in laboratory conditions. Catalases are also not essential for cellulose or fatty acid assimilation. In contrast, they are strictly required for efficient utilization of more complex biomass like wood shavings by allowing growth in the presence of lignin. The secreted CATB and cytosolic CAT2 are the major catalases implicated in peroxide resistance, while CAT2 is the major player during complex biomass assimilation. Our results suggest that P. anserina produces external H(2O(2 to assimilate complex biomass and that catalases are necessary to protect the cells during this process. In addition, the phenotypes of strains lacking only one catalase gene suggest that a decrease of catalase activity improves the capacity of the fungus to degrade complex biomass.

  9. PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

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    Kicka, Sébastien; Silar, Philippe

    2004-03-01

    MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.

  10. The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.

    Science.gov (United States)

    Timpano, Hélène; Chan Ho Tong, Laetitia; Gautier, Valérie; Lalucque, Hervé; Silar, Philippe

    2016-09-01

    In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes.

  11. COnstructing Proxy Records from Age models (COPRA

    Directory of Open Access Journals (Sweden)

    S. F. M. Breitenbach

    2012-10-01

    Full Text Available Reliable age models are fundamental for any palaeoclimate reconstruction. Available interpolation procedures between age control points are often inadequately reported, and very few translate age uncertainties to proxy uncertainties. Most available modeling algorithms do not allow incorporation of layer counted intervals to improve the confidence limits of the age model in question.

    We present a framework that allows detection and interactive handling of age reversals and hiatuses, depth-age modeling, and proxy-record reconstruction. Monte Carlo simulation and a translation procedure are used to assign a precise time scale to climate proxies and to translate dating uncertainties to uncertainties in the proxy values. The presented framework allows integration of incremental relative dating information to improve the final age model. The free software package COPRA1.0 facilitates easy interactive usage.

  12. COnstructing Proxy-Record Age models (COPRA

    Directory of Open Access Journals (Sweden)

    S. F. M. Breitenbach

    2012-06-01

    Full Text Available Reliable age models are fundamental for any palaeoclimate reconstruction. Interpolation procedures between age control points are often inadequately reported, and available modeling algorithms do not allow incorporation of layer counted intervals to improve the confidence limits of the age model in question. We present a modeling approach that allows automatic detection and interactive handling of outliers and hiatuses. We use Monte Carlo simulation to assign an absolute time scale to climate proxies by conferring the dating uncertainties to uncertainties in the proxy values. The algorithm allows us to integrate incremental relative dating information to improve the final age model. The software package COPRA1.0 facilitates easy interactive usage.

  13. Aging Successfully: A Four-Factor Model

    Science.gov (United States)

    Lee, Pai-Lin; Lan, William; Yen, Tung-Wen

    2011-01-01

    The study was designed to validate a model for a successful aging process and examine the gender differences in the aging process. Three hundred twelve participants who were 65 or older completed a Taiwan Social Change Survey that measures four factors that define successful aging process: including physical, psychological, social support, and…

  14. Modelling the molecular mechanisms of aging.

    Science.gov (United States)

    Mc Auley, Mark T; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M; Morgan, Amy E; Proctor, Carole J

    2017-02-28

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.

  15. Mouse models and aging: longevity and progeria.

    Science.gov (United States)

    Liao, Chen-Yu; Kennedy, Brian K

    2014-01-01

    Aging is a complex, multifactorial process that is likely influenced by the activities of a range of biological pathways. Genetic approaches to identify genes modulating longevity have been highly successful and recent efforts have extended these studies to mammalian aging. A variety of genetic models have been reported to have enhanced lifespan and, similarly, many genetic interventions lead to progeroid phenotypes. Here, we detail and evaluate both sets of models, focusing on the insights they provide about the molecular processes modulating aging and the extent to which mutations conferring progeroid pathologies really phenocopy accelerated aging.

  16. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  17. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  18. Confronting Substellar Theoretical Models with Stellar Ages

    CERN Document Server

    Dupuy, Trent J; Ireland, Michael J

    2009-01-01

    By definition, brown dwarfs never reach the main-sequence, cooling and dimming over their entire lifetime, thus making substellar models challenging to test because of the strong dependence on age. Currently, most brown dwarfs with independently determined ages are companions to nearby stars, so stellar ages are at the heart of the effort to test substellar models. However, these models are only fully constrained if both the mass and age are known. We have used the Keck adaptive optics system to monitor the orbit of HD 130948BC, a brown dwarf binary that is a companion to the young solar analog HD 130948A. The total dynamical mass of 0.109+/-0.003 Msun shows that both components are substellar, and the ensemble of available age indicators from the primary star suggests an age comparable to the Hyades, with the most precise age being 0.79 Gyr based on gyrochronology. Therefore, HD 130948BC is unique among field L and T dwarfs as it possesses a well-determined mass, luminosity, and age. Our results indicate tha...

  19. A Model of Spirituality for Ageing Muslims.

    Science.gov (United States)

    Ahmad, Mahjabeen; Khan, Shamsul

    2016-06-01

    Spirituality's influence on general well-being and its association with healthy ageing has been studied extensively. However, a different perspective has to be brought in when dealing with spirituality issues of ageing Muslims. Central to this perspective is the intertwining of religion and spirituality in Islam. This article will contribute to the understanding of the nature of Islamic spirituality and its immense importance in the life of a practicing ageing Muslim. Consequently, it will help care providers to include appropriate spiritual care in the care repertoire of a Muslim care recipient. It is assumed that the framework for a model of spirituality based on Islamic religious beliefs would help contextualise the relationship between spirituality and ageing Muslims. Not only challenges, but also the opportunities that old age provides for charting the spiritual journey have underpinned this model.

  20. Species ages in neutral biodiversity models.

    Science.gov (United States)

    Chisholm, Ryan A; O'Dwyer, James P

    2014-05-01

    Biogeography seeks to understand the mechanisms that drive biodiversity across long temporal and large spatial scales. Theoretical models of biogeography can be tested by comparing their predictions of quantities such as species ages against empirical estimates. It has previously been claimed that the neutral theory of biodiversity and biogeography predicts species ages that are unrealistically long. Any improved theory of biodiversity must rectify this problem, but first it is necessary to quantify the problem precisely. Here we provide analytical expressions for species ages in neutral biodiversity communities. We analyse a spatially implicit metacommunity model and solve for both the zero-sum and non-zero-sum cases. We explain why our new expressions are, in the context of biodiversity, usually more appropriate than those previously imported from neutral molecular evolution. Because of the time symmetry of the spatially implicit neutral model, our expressions also lead directly to formulas for species persistence times and species lifetimes. We use our new expressions to estimate species ages of forest trees under a neutral model and find that they are about an order of magnitude shorter than those predicted previously but still unrealistically long. In light of our results, we discuss different models of biogeography that may solve the problem of species ages.

  1. A model for two-step ageing

    Indian Academy of Sciences (India)

    K T Kashyap; C Ramachandra; B Chatterji; S Lele

    2000-10-01

    In commercial practice, two-step ageing is commonly used in Al–Zn–Mg alloys to produce a fine dispersion of ′ precipitates to accentuate the mechanical properties and resistance to stress corrosion cracking. While this is true in Al–Zn–Mg alloys, two-step ageing leads to inferior properties in Al–Mg–Si alloys. This controversial behaviour in different alloys can be explained by Pashley’s Kinetic model. Pashley’s model addresses the stability of clusters after two-step ageing. In the development of the model, the surface energy term between cluster and matrix is taken into account while the coherency strains between the cluster and matrix are not considered. In the present work, a model is developed which takes into account the coherency strains between cluster and matrix and defines a new stability criterion, inclusive of strain energy term. Experiments were done on AA 7010 aluminium alloy by carrying out a two-step ageing treatment and the results fit the new stability criterion. Thus it is found that the new model for two-step ageing is verified in the case of Al–Zn–Mg alloy.

  2. Are invertebrates relevant models in ageing research?

    DEFF Research Database (Denmark)

    Erdogan, Cihan Suleyman; Hansen, Benni Winding; Vang, Ole

    2016-01-01

    Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR...... the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning...... the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan...

  3. A CONTINUUM DAMAGE MODEL OF AGING CONCRETE

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhenyang; Xie Huicai; Xu Tao; Yu Jie; Cai Changan

    2001-01-01

    There is up to now no constitutive model in the current theories of CDM that could give a description for the degradation of aging concrete. The two internal state variables β and ω are introduced in this paper. β is called cohesion variable as an additional kinematic parameter, reflecting the cohesion state among material particles. ω is called damage factor for micro-defects such as voids.Then a damage model and a series of constitutive equations are developed on Continuum Mechanics.The model proposed could give a valid description for the whole-course-degradation of aging concrete due tochemical and mechanical actions. Finally, the validity of the model is evaluated by an example and experimental results.

  4. An age structured demographic model of technology

    CERN Document Server

    Mercure, J -F

    2013-01-01

    At the heart of technology transitions lie complex processes of technology choices. Understanding and planning sustainability transitions requires modelling work, which necessitates a theory of technology substitution. A theoretical model of technological change and turnover is presented, intended as a methodological paradigm shift from widely used conventional modelling approaches such as cost optimisation. It follows the tradition of evolutionary economics and evolutionary game theory, using ecological population growth dynamics to represent the evolution of technology populations in the marketplace, with substitutions taking place at the level of the decision-maker. Extended to use principles of human demography or the age structured evolution of species in interacting ecosystems, this theory is built from first principles, and through an appropriate approximation, reduces to a form identical to empirical models of technology diffusion common in the technology transitions literature. Using an age structure...

  5. Love Kills:. Simulations in Penna Ageing Model

    Science.gov (United States)

    Stauffer, Dietrich; Cebrat, Stanisław; Penna, T. J. P.; Sousa, A. O.

    The standard Penna ageing model with sexual reproduction is enlarged by adding additional bit-strings for love: Marriage happens only if the male love strings are sufficiently different from the female ones. We simulate at what level of required difference the population dies out.

  6. Systematic gene deletions evidences that laccases are involved in several stages of wood degradation in the filamentous fungus Podospora anserina.

    Science.gov (United States)

    Xie, Ning; Chapeland-Leclerc, Florence; Silar, Philippe; Ruprich-Robert, Gwenaël

    2014-01-01

    Transformation of plant biomass into biofuels may supply environmentally friendly alternative biological sources of energy. Laccases are supposed to be involved in the lysis of lignin, a prerequisite step for efficient breakdown of cellulose into fermentable sugars. The role in development and plant biomass degradation of the nine canonical laccases belonging to three different subfamilies and one related multicopper oxidase of the Ascomycota fungus Podospora anserina was investigated by targeted gene deletion. The 10 genes were inactivated singly, and multiple mutants were constructed by genetic crosses. lac6(Δ), lac8(Δ) and mco(Δ) mutants were significantly reduced in their ability to grow on lignin-containing materials, but also on cellulose and plastic. Furthermore, lac8(Δ), lac7(Δ), mco(Δ) and lac6(Δ) mutants were defective towards resistance to phenolic substrates and H2 O2 , which may also impact lignocellulose breakdown. Double and multiple mutants were generally more affected than single mutants, evidencing redundancy of function among laccases. Our study provides the first genetic evidences that laccases are major actors of wood utilization in a fungus and that they have multiple roles during this process apart from participation in lignin lysis.

  7. Characterization of the genomic organization of the region bordering the centromere of chromosome V of Podospora anserina by direct sequencing.

    Science.gov (United States)

    Silar, Philippe; Barreau, Christian; Debuchy, Robert; Kicka, Sébastien; Turcq, Béatrice; Sainsard-Chanet, Annie; Sellem, Carole H; Billault, Alain; Cattolico, Laurence; Duprat, Simone; Weissenbach, Jean

    2003-08-01

    A Podospora anserina BAC library of 4800 clones has been constructed in the vector pBHYG allowing direct selection in fungi. Screening of the BAC collection for centromeric sequences of chromosome V allowed the recovery of clones localized on either sides of the centromere, but no BAC clone was found to contain the centromere. Seven BAC clones containing 322,195 and 156,244bp from either sides of the centromeric region were sequenced and annotated. One 5S rRNA gene, 5 tRNA genes, and 163 putative coding sequences (CDS) were identified. Among these, only six CDS seem specific to P. anserina. The gene density in the centromeric region is approximately one gene every 2.8kb. Extrapolation of this gene density to the whole genome of P. anserina suggests that the genome contains about 11,000 genes. Synteny analyses between P. anserina and Neurospora crassa show that co-linearity extends at the most to a few genes, suggesting rapid genome rearrangements between these two species.

  8. A general framework for optimization of probes for gene expression microarray and its application to the fungus Podospora anserina

    Directory of Open Access Journals (Sweden)

    Bidard Frédérique

    2010-06-01

    Full Text Available Abstract Background The development of new microarray technologies makes custom long oligonucleotide arrays affordable for many experimental applications, notably gene expression analyses. Reliable results depend on probe design quality and selection. Probe design strategy should cope with the limited accuracy of de novo gene prediction programs, and annotation up-dating. We present a novel in silico procedure which addresses these issues and includes experimental screening, as an empirical approach is the best strategy to identify optimal probes in the in silico outcome. Findings We used four criteria for in silico probe selection: cross-hybridization, hairpin stability, probe location relative to coding sequence end and intron position. This latter criterion is critical when exon-intron gene structure predictions for intron-rich genes are inaccurate. For each coding sequence (CDS, we selected a sub-set of four probes. These probes were included in a test microarray, which was used to evaluate the hybridization behavior of each probe. The best probe for each CDS was selected according to three experimental criteria: signal-to-noise ratio, signal reproducibility, and representative signal intensities. This procedure was applied for the development of a gene expression Agilent platform for the filamentous fungus Podospora anserina and the selection of a single 60-mer probe for each of the 10,556 P. anserina CDS. Conclusions A reliable gene expression microarray version based on the Agilent 44K platform was developed with four spot replicates of each probe to increase statistical significance of analysis.

  9. Bilirubin oxidase-like proteins from Podospora anserina: promising thermostable enzymes for application in transformation of plant biomass.

    Science.gov (United States)

    Xie, Ning; Ruprich-Robert, Gwenaël; Silar, Philippe; Chapeland-Leclerc, Florence

    2015-03-01

    Plant biomass degradation by fungi is a critical step for production of biofuels, and laccases are common ligninolytic enzymes envisioned for ligninolysis. Bilirubin oxidases (BODs)-like are related to laccases, but their roles during lignocellulose degradation have not yet been fully investigated. The two BODs of the ascomycete fungus Podospora anserina were characterized by targeted gene deletions. Enzymatic assay revealed that the bod1(Δ) and bod2(Δ) mutants lost partly a thermostable laccase activity. A triple mutant inactivated for bod1, bod2 and mco, a previously investigated multicopper oxidase gene distantly related to laccases, had no thermostable laccase activity. The pattern of fruiting body production in the bod1(Δ) bod2(Δ) double mutant was changed. The bod1(Δ) and bod2(Δ) mutants were reduced in their ability to grow on ligneous and cellulosic materials. Furthermore, bod1(Δ) and bod2(Δ) mutants were defective towards resistance to phenolic substrates and H2 O2 , which may also impact lignocellulose breakdown. Double and triple mutants were more affected than single mutants, evidencing redundancy of function among BODs and mco. Overall, the data show that bod1, bod2 and mco code for non-canonical thermostable laccases that participate in the degradation of lignocellulose. Thanks to their thermal stability, these enzymes may be more promising candidate for biotechnological application than canonical laccases.

  10. Calibration of Models Using Groundwater Age (Invited)

    Science.gov (United States)

    Sanford, W. E.

    2009-12-01

    Water-resource managers are frequently concerned with the long-term ability of a groundwater system to deliver volumes of water for both humans and ecosystems under natural and anthropogenic stresses. Analysis of how a groundwater system responds to such stresses usually involves the construction and calibration of a numerical groundwater-flow model. The calibration procedure usually involves the use of both groundwater-level and flux observations. Water-level data are often more abundant, and thus the availability of flux data can be critical, with well discharge and base flow to streams being most often available. Lack of good flux data however is a common occurrence, especially in more arid climates where the sustainability of the water supply may be even more in question. Environmental tracers are frequently being used to estimate the “age” of a water sample, which represents the time the water has been in the subsurface since its arrival at the water table. Groundwater ages provide flux-related information and can be used successfully to help calibrate groundwater models if porosity is well constrained, especially when there is a paucity of other flux data. As several different methods of simulating groundwater age and tracer movement are possible, a review is presented here of the advantages, disadvantages, and potential pitfalls of the various numerical and tracer methods used in model calibration. The usefulness of groundwater ages for model calibration depends on the ability both to interpret a tracer so as to obtain an apparent observed age, and to use a numerical model to obtain an equivalent simulated age observation. Different levels of simplicity and assumptions accompany different methods for calculating the equivalent simulated age observation. The advantages of computational efficiency in certain methods can be offset by error associated with the underlying assumptions. Advective travel-time calculation using path-line tracking in finite

  11. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  12. Centenarians - a useful model for healthy aging?

    DEFF Research Database (Denmark)

    Engberg, Henriette; Oksuzyan, Anna; Jeune, Bernard;

    2009-01-01

    Centenarians surpass the current human life expectancy with about 20-25 years. However, whether centenarians represent healthy aging still remains an open question. Previous studies have been hampered by a number of methodological shortcomings such as a cross-sectional design and lack...... of an appropriate control group. In a longitudinal population-based cohort, it was examined whether the centenarian phenotype may be a useful model for healthy aging. The study was based on a completefollow up of 39 945 individuals alive in the Danish 1905 birth cohort on January 1, 1977 identified through...... with 68.4% among individuals who died in their early 80s. This trend was evident in both sexes. As a result of their lower hospitalization rates and length of stay in hospital compared with their contemporaries, who died at younger ages, Danish centenarians represent healthy agers. Centenarians constitute...

  13. Biological Aging - Criteria for Modeling and a New Mechanistic Model

    Science.gov (United States)

    Pletcher, Scott D.; Neuhauser, Claudia

    To stimulate interaction and collaboration across scientific fields, we introduce a minimum set of biological criteria that theoretical models of aging should satisfy. We review results of several recent experiments that examined changes in age-specific mortality rates caused by genetic and environmental manipulation. The empirical data from these experiments is then used to test mathematical models of aging from several different disciplines, including molecular biology, reliability theory, physics, and evolutionary biology/population genetics. We find that none of the current models are consistent with all of the published experimental findings. To provide an example of how our criteria might be applied in practice, we develop a new conceptual model of aging that is consistent with our observations.

  14. Identification and characterization of PaMTH1, a putative O-methyltransferase accumulating during senescence of Podospora anserina cultures

    DEFF Research Database (Denmark)

    Averbeck, N B; Jensen, Ole Nørregaard; Mann, M

    2000-01-01

    A differential protein display screen resulted in the identification of a 27-kDa protein which strongly accumulates during the senescence of Podospora anserina cultures grown under standard conditions. After partial determination of the amino-acid sequence by mass-spectrometry analysis of trypsin...... by a discontinuous gene, PaMth1, capable of coding for 240 amino acids. The first three amino-terminal residues appear to be removed post-translationally. The deduced amino-acid sequence shows significant homology to S-adenosylmethionine (SAM)-dependent methyltransferases. We hypothesize that the 27-kDa protein, Pa...

  15. Identification of PaPKS1, a polyketide synthase involved in melanin formation and its use as a genetic tool in Podospora anserina.

    Science.gov (United States)

    Coppin, Evelyne; Silar, Philippe

    2007-08-01

    In the filamentous fungus Podospora anserina, many pigmentation mutations map to the median region of the complex locus '14', called segment '29'. The data presented in this paper show that segment 29 corresponds to a gene encoding a polyketide synthase, designated PaPKS1, and identifies two mutations that completely or partially abolish the activity of the PaPKS1 polypeptide. We present evidence that the P. anserina green pigment is a (DHN)-melanin. Using the powerful genetic system of PaPKS1 cloning, we demonstrate that in P. anserina trans-duplicated sequences are subject to the RIP process as previously demonstrated for the cis-duplicated regions.

  16. Aging, Breast Cancer and the Mouse Model

    Science.gov (United States)

    2005-05-01

    Presenescent or senescent hBF (1.2 or 18x×10 4/well, respectively) [M, Stampfer , P. Yaswen, Lawrence Berkeley National Laboratory wdre suspended in 60 l cold...2.8 1 2.8 Inducing a human-like senescent phenotype in mouse fibroblasts Jean-Philihoo Copp , Simona Parrinello, Ana Krtolica, Christopher K. Patil...MAMMARY EPITHELIAL CELL PROLIFERATION AND TUMORIGENESIS: A MOUSE MODEL FOR HUMAN AGING. Jean-Philippe Coppe, Simona Parrinello, Ana Krtolica, Christopher

  17. Micromechanical Modeling of Concrete at Early Age

    Science.gov (United States)

    Tuleubekov, Kairat

    The focus of this research is a micromechanical characterization of Portland cement concrete at early age (less than 28 days). Concrete's viscoelastic properties change significantly at early age due to solidification of its matrix component. Bazant's solidification theory models concrete as a material solidifying in time. This approach is generalized to a three-dimensional characterization of a composite material with a solidifying matrix and elastic inclusions. An integral constitutive relationship was obtained using a generalized correspondence principle and homogenization techniques for elastic composite materials. In light of this approach, effective creep properties of composite spherical assemblage with an aging matrix are obtained. In addition, the elastic Hashin-Monteiro model is generalized to account for the effect of the interfacial transition zone properties on concrete creep. An effective computational platform was developed to evaluate operator expressions in order to obtain relaxation and creep functions numerically. Through numerical examples, it is shown that triaxial generalization of Bazant's solidification model enables robust and computationally efficient prediction of creep deformations in Portland cement concrete.

  18. Maintaining two mating types: structure of the mating type locus and its role in heterokaryosis in Podospora anserina.

    Science.gov (United States)

    Grognet, Pierre; Bidard, Frédérique; Kuchly, Claire; Tong, Laetitia Chan Ho; Coppin, Evelyne; Benkhali, Jinane Ait; Couloux, Arnaud; Wincker, Patrick; Debuchy, Robert; Silar, Philippe

    2014-05-01

    Pseudo-homothallism is a reproductive strategy elected by some fungi producing heterokaryotic sexual spores containing genetically different but sexually compatible nuclei. This lifestyle appears as a compromise between true homothallism (self-fertility with predominant inbreeding) and complete heterothallism (with exclusive outcrossing). However, pseudohomothallic species face the problem of maintaining heterokaryotic mycelia to fully benefit from this lifestyle, as homokaryons are self-sterile. Here, we report on the structure of chromosome 1 in mat+ and mat- isolates of strain S of the pseudohomothallic fungus Podospora anserina. Chromosome 1 contains either one of the mat+ and mat- mating types of P. anserina, which is mostly found in nature as a mat+/mat- heterokaryotic mycelium harboring sexually compatible nuclei. We identified a "mat" region ∼0.8 Mb long, devoid of meiotic recombination and containing the mating-type idiomorphs, which is a candidate to be involved in the maintenance of the heterokaryotic state, since the S mat+ and S mat- strains have different physiology that may enable hybrid-vigor-like phenomena in the heterokaryons. The mat region contains 229 coding sequences. A total of 687 polymorphisms were detected between the S mat+ and S mat- chromosomes. Importantly, the mat region is colinear between both chromosomes, which calls for an original mechanism of recombination inhibition. Microarray analyses revealed that 10% of the P. anserina genes have different transcriptional profiles in S mat+ and S mat-, in line with their different phenotypes. Finally, we show that the heterokaryotic state is faithfully maintained during mycelium growth of P. anserina, yet mat+/mat+ and mat-/mat- heterokaryons are as stable as mat+/mat- ones, evidencing a maintenance of heterokaryosis that does not rely on fitness-enhancing complementation between the S mat+ and S mat- strains.

  19. Biological roles of the Podospora anserina mitochondrial Lon protease and the importance of its N-domain.

    Directory of Open Access Journals (Sweden)

    Céline Adam

    Full Text Available Mitochondria have their own ATP-dependent proteases that maintain the functional state of the organelle. All multicellular eukaryotes, including filamentous fungi, possess the same set of mitochondrial proteases, unlike in unicellular yeasts, where ClpXP, one of the two matricial proteases, is absent. Despite the presence of ClpXP in the filamentous fungus Podospora anserina, deletion of the gene encoding the other matricial protease, PaLon1, leads to lethality at high and low temperatures, indicating that PaLON1 plays a main role in protein quality control. Under normal physiological conditions, the PaLon1 deletion is viable but decreases life span. PaLon1 deletion also leads to defects in two steps during development, ascospore germination and sexual reproduction, which suggests that PaLON1 ensures important regulatory functions during fungal development. Mitochondrial Lon proteases are composed of a central ATPase domain flanked by a large non-catalytic N-domain and a C-terminal protease domain. We found that three mutations in the N-domain of PaLON1 affected fungal life cycle, PaLON1 protein expression and mitochondrial proteolytic activity, which reveals the functional importance of the N-domain of the mitochondrial Lon protease. All PaLon1 mutations affected the C-terminal part of the N-domain. Considering that the C-terminal part is predicted to have an α helical arrangement in which the number, length and position of the helices are conserved with the solved structure of its bacterial homologs, we propose that this all-helical structure participates in Lon substrate interaction.

  20. Speciation Effect in the Penna Aging Model

    Science.gov (United States)

    Łaszkiewicz, A.; Szymczak, Sz.; Cebrat, S.

    We have simulated the evolution of diploid, sexually reproducing populations using the Penna model of aging. We have noted that diminishing the recombination frequency during the gamete production generates a specific diversity of genomes in the populations. When two populations independently evolving for some time were mixed in one environmental niche of the limited size and crossbreeding between them was allowed, the average lifespan of hybrids was significantly shorter than the lifespan of the individuals of parental lines. Another effect of higher hybrid mortality is the faster elimination of one parental line from the shared environment. The two populations living in one environment co-exist much longer if they are genetically separated — they compete as two species instead of crossbreeding. This effect can be considered as the first step to speciation — any barrier eliminating crossbreeding between these populations, leading to speciation, would favor the populations.

  1. Age dependent dietary assessment model (AGE MODE). Folate and vitamin A as examples

    NARCIS (Netherlands)

    Waijers PMCM; Dekkers ALM; Boer JMA; van Rossum CTM; CVG

    2007-01-01

    Dit rapport beschrijft de werking van het model AGE MODE. AGE MODE is een methode om de gebruikelijke inneming van microvoedingsstoffen, vitaminen en mineralen, te schatten en te toetsen aan de voedingsnorm.
    AGE MODE is ontwikkeld door het RIVM. AGE MODE is een kwantitatieve methode om de

  2. A compositional and dynamic model for face aging.

    Science.gov (United States)

    Suo, Jinli; Zhu, Song-Chun; Shan, Shiguang; Chen, Xilin

    2010-03-01

    In this paper, we present a compositional and dynamic model for face aging. The compositional model represents faces in each age group by a hierarchical And-Or graph, in which And nodes decompose a face into parts to describe details (e.g., hair, wrinkles, etc.) crucial for age perception and Or nodes represent large diversity of faces by alternative selections. Then a face instance is a transverse of the And-Or graph-parse graph. Face aging is modeled as a Markov process on the parse graph representation. We learn the parameters of the dynamic model from a large annotated face data set and the stochasticity of face aging is modeled in the dynamics explicitly. Based on this model, we propose a face aging simulation and prediction algorithm. Inversely, an automatic age estimation algorithm is also developed under this representation. We study two criteria to evaluate the aging results using human perception experiments: 1) the accuracy of simulation: whether the aged faces are perceived of the intended age group, and 2) preservation of identity: whether the aged faces are perceived as the same person. Quantitative statistical analysis validates the performance of our aging model and age estimation algorithm.

  3. Protoplasmic Incompatibility in PODOSPORA ANSERINA: a Possible Function for Incompatibility Genes.

    Science.gov (United States)

    Boucherie, H; Bernet, J

    1980-10-01

    The suppression of protoplasmic incompatibility resulting from nonallelic gene interactions has been obtained by the coupled effect of mutations in the modA and modB genes (Bernet 1971). Due to their female sterility, modA modB strains provide an experimental tool to determine whether or not the mod and incompatibility loci are involved in a function other than protoplasmic incompatibility. Present results show that modA modB female sterility is a nonautonomous trait since heterokaryotic mycelia that include a modA modB nucleus and a female fertile nucleus (wild-type, modA or modB) produce modA modB protoperithecia, which are also formed by culture on medium supplemented with specific amino acids. Using modA modB strains, which are sterile at 32 degrees and fertile at 26 degrees , we have shown that the mod genes have no specific sequential timing. Indeed, the mod mutations may prevent the achievement of the female sexual cycle at any developmental stage from before early differentiation of protoperithecia until ascospore maturation. Employing different modA and modB mutations, we have shown that protoperithecia in modA modB cultures are generally distributed in female fertile rings; this result indicates that protoperithecia occur only in mycelial areas that have a restricted range of age at the time that modA modB thalli complete growth. Furthermore, nonsense mutations of incompatibility genes suppress the modA modB female fertile rings or restrict their width, suggesting that incompatibility loci, like the mod loci, are involved in protoperithecium formation. Taken together, these results lead to the postulate that mod and incompatibility genes do not determine, sensu stricto, protoperithecial function, as previously supposed (Boucherie and Bernet 1974), but may be involved in the homeostatic control of stationary cell functions essential for the complete development of the female sexual cycle.

  4. Biological implications of the Weibull and Gompertz models of aging.

    Science.gov (United States)

    Ricklefs, Robert E; Scheuerlein, Alex

    2002-02-01

    Gompertz and Weibull functions imply contrasting biological causes of demographic aging. The terms describing increasing mortality with age are multiplicative and additive, respectively, which could result from an increase in the vulnerability of individuals to extrinsic causes in the Gompertz model and the predominance of intrinsic causes at older ages in the Weibull model. Experiments that manipulate extrinsic mortality can distinguish these biological models. To facilitate analyses of experimental data, we defined a single index for the rate of aging (omega) for the Weibull and Gompertz functions. Each function described the increase in aging-related mortality in simulated ages at death reasonably well. However, in contrast to the Weibull omega(W), the Gompertz omega(G) was sensitive to variation in the initial mortality rate independently of aging-related mortality. Comparisons between wild and captive populations appear to support the intrinsic-causes model for birds, but give mixed support for both models in mammals.

  5. A two-age-classes dengue transmission model

    NARCIS (Netherlands)

    Supriatna, A.K.; Soewono, E.; Gils, van S.A.

    2008-01-01

    In this paper, we discuss a two-age-classes dengue transmission model with vaccination. The reason to divide the human population into two age classes is for practical purpose, as vaccination is usually concentrated in one age class. We assume that a constant rate of individuals in the child-class i

  6. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    Directory of Open Access Journals (Sweden)

    K. M. Rice

    2014-01-01

    Full Text Available Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging.

  7. Age and gender specific biokinetic model for strontium in humans

    Energy Technology Data Exchange (ETDEWEB)

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  8. Successful aging as a continuum of functional independence: lessons from physical disability models of aging.

    NARCIS (Netherlands)

    Lowry, K.A.; Vallejo, A.N.; Studenski, S.A.

    2012-01-01

    Successful aging is a multidimensional construct that could be viewed as a continuum of achievement. Based on the disability model proposed by the WHO International Classification of Functioning, Disability and Health, successful aging includes not only the presence or absence of disease, but also a

  9. The Healthy Ageing Model: health behaviour change for older adults.

    Science.gov (United States)

    Potempa, Kathleen M; Butterworth, Susan W; Flaherty-Robb, Marna K; Gaynor, William L

    2010-01-01

    Proposed is a model of primary care for older adults with chronic health conditions that focuses on active engagement in health care. The Healthy Ageing Model is anchored in established theory on motivation and health behaviour change. The model draws on empirical and applied clinical underpinnings in such diverse areas as health promotion and education, treatment of addictions or obesity, management of chronic diseases, goal-setting, and coaching techniques. The conceptual foundation for the Healthy Ageing Model is described first, followed by a brief description of the key characteristics of the model. In conclusion, suggestions are offered for the clinical application and for further developing the model.

  10. Numerical solution of the Penna model of biological aging with age-modified mutation rate

    Science.gov (United States)

    Magdoń-Maksymowicz, M. S.; Maksymowicz, A. Z.

    2009-06-01

    In this paper we present results of numerical calculation of the Penna bit-string model of biological aging, modified for the case of a -dependent mutation rate m(a) , where a is the parent’s age. The mutation rate m(a) is the probability per bit of an extra bad mutation introduced in offspring inherited genome. We assume that m(a) increases with age a . As compared with the reference case of the standard Penna model based on a constant mutation rate m , the dynamics of the population growth shows distinct changes in age distribution of the population. Here we concentrate on mortality q(a) , a fraction of items eliminated from the population when we go from age (a) to (a+1) in simulated transition from time (t) to next time (t+1) . The experimentally observed q(a) dependence essentially follows the Gompertz exponential law for a above the minimum reproduction age. Deviation from the Gompertz law is however observed for the very old items, close to the maximal age. This effect may also result from an increase in mutation rate m with age a discussed in this paper. The numerical calculations are based on analytical solution of the Penna model, presented in a series of papers by Coe [J. B. Coe, Y. Mao, and M. E. Cates, Phys. Rev. Lett. 89, 288103 (2002)]. Results of the numerical calculations are supported by the data obtained from computer simulation based on the solution by Coe

  11. Lithium battery aging model based on Dakin's degradation approach

    Science.gov (United States)

    Baghdadi, Issam; Briat, Olivier; Delétage, Jean-Yves; Gyan, Philippe; Vinassa, Jean-Michel

    2016-09-01

    This paper proposes and validates a calendar and power cycling aging model for two different lithium battery technologies. The model development is based on previous SIMCAL and SIMSTOCK project data. In these previous projects, the effect of the battery state of charge, temperature and current magnitude on aging was studied on a large panel of different battery chemistries. In this work, data are analyzed using Dakin's degradation approach. In fact, the logarithms of battery capacity fade and the increase in resistance evolves linearly over aging. The slopes identified from straight lines correspond to battery aging rates. Thus, a battery aging rate expression function of aging factors was deduced and found to be governed by Eyring's law. The proposed model simulates the capacity fade and resistance increase as functions of the influencing aging factors. Its expansion using Taylor series was consistent with semi-empirical models based on the square root of time, which are widely studied in the literature. Finally, the influence of the current magnitude and temperature on aging was simulated. Interestingly, the aging rate highly increases with decreasing and increasing temperature for the ranges of -5 °C-25 °C and 25 °C-60 °C, respectively.

  12. Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models

    Directory of Open Access Journals (Sweden)

    Yuqing Dong

    2012-01-01

    Full Text Available Aging is a complex and inevitable biological process that is associated with numerous chronically debilitating health effects. Development of effective interventions for promoting healthy aging is an active but challenging area of research. Mechanistic studies in various model organisms, noticeably two invertebrates, Caenorhabditis elegans and Drosophila melanogaster, have identified many genes and pathways as well as dietary interventions that modulate lifespan and healthspan. These studies have shed light on some of the mechanisms involved in aging processes and provide valuable guidance for developing efficacious aging interventions. Nutraceuticals made from various plants contain a significant amount of phytochemicals with diverse biological activities. Phytochemicals can modulate many signaling pathways that exert numerous health benefits, such as reducing cancer incidence and inflammation, and promoting healthy aging. In this paper, we outline the current progress in aging intervention studies using nutraceuticals from an evolutionary perspective in invertebrate models.

  13. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  14. Multiscale Concrete Modeling of Aging Degradation

    Energy Technology Data Exchange (ETDEWEB)

    Hammi, Yousseff [Mississippi State Univ., Mississippi State, MS (United States); Gullett, Philipp [Mississippi State Univ., Mississippi State, MS (United States); Horstemeyer, Mark F. [Mississippi State Univ., Mississippi State, MS (United States)

    2015-07-31

    In this work a numerical finite element framework is implemented to enable the integration of coupled multiscale and multiphysics transport processes. A User Element subroutine (UEL) in Abaqus is used to simultaneously solve stress equilibrium, heat conduction, and multiple diffusion equations for 2D and 3D linear and quadratic elements. Transport processes in concrete structures and their degradation mechanisms are presented along with the discretization of the governing equations. The multiphysics modeling framework is theoretically extended to the linear elastic fracture mechanics (LEFM) by introducing the eXtended Finite Element Method (XFEM) and based on the XFEM user element implementation of Giner et al. [2009]. A damage model that takes into account the damage contribution from the different degradation mechanisms is theoretically developed. The total contribution of damage is forwarded to a Multi-Stage Fatigue (MSF) model to enable the assessment of the fatigue life and the deterioration of reinforced concrete structures in a nuclear power plant. Finally, two examples are presented to illustrate the developed multiphysics user element implementation and the XFEM implementation of Giner et al. [2009].

  15. Selection Experiments in the Penna Model for Biological Aging

    Science.gov (United States)

    Medeiros, G.; Idiart, M. A.; de Almeida, R. M. C.

    We consider the Penna model for biological aging to investigate correlations between early fertility and late life survival rates in populations at equilibrium. We consider inherited initial reproduction ages together with a reproduction cost translated in a probability that mother and offspring die at birth, depending on the mother age. For convenient sets of parameters, the equilibrated populations present genetic variability in what regards both genetically programmed death age and initial reproduction age. In the asexual Penna model, a negative correlation between early life fertility and late life survival rates naturally emerges in the stationary solutions. In the sexual Penna model, selection experiments are performed where individuals are sorted by initial reproduction age from the equilibrated populations and the separated populations are evolved independently. After a transient, a negative correlation between early fertility and late age survival rates also emerges in the sense that populations that start reproducing earlier present smaller average genetically programmed death age. These effects appear due to the age structure of populations in the steady state solution of the evolution equations. We claim that the same demographic effects may be playing an important role in selection experiments in the laboratory.

  16. Bayesian Age-Period-Cohort Modeling and Prediction - BAMP

    Directory of Open Access Journals (Sweden)

    Volker J. Schmid

    2007-10-01

    Full Text Available The software package BAMP provides a method of analyzing incidence or mortality data on the Lexis diagram, using a Bayesian version of an age-period-cohort model. A hierarchical model is assumed with a binomial model in the first-stage. As smoothing priors for the age, period and cohort parameters random walks of first and second order, with and without an additional unstructured component are available. Unstructured heterogeneity can also be included in the model. In order to evaluate the model fit, posterior deviance, DIC and predictive deviances are computed. By projecting the random walk prior into the future, future death rates can be predicted.

  17. The heuristic value of redundancy models of aging

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Briga, Michael; Verhulst, Simon

    2015-01-01

    Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. T

  18. Model-Based Exploration of Societal Aging in the Netherlands

    NARCIS (Netherlands)

    Pruyt, E.; Logtens, T.W.A.

    2015-01-01

    Mismanagement of societal aging is an important threat to health care, social security, and the economy of many nations. A System Dynamics simulation model related to societal aging in the Netherlands and its implications for the Dutch welfare system is used here to generate exploratory scenarios an

  19. The role of forest age in earth system models

    Science.gov (United States)

    Poulter, B.; Bellassen, V.; Lin, X.; Luyssaert, S.; Nachin, B.; Pederson, N.; Shchepashchenko, D.; Shvidenko, A.; Ciais, P.

    2012-12-01

    The age of a forest has a principal role in determining the magnitude of carbon stocks and fluxes. As forests grow older, carbon tends to accumulate in above and belowground biomass causing changes in forest canopy complexity, nutrient pools, and the balance between carbon uptake and release. While age is a standard variable for forestry models, the present generation of earth system models neglects a representation of forest age for several reasons. These include the challenge in representing sub-grid cell ecosystem heterogeneity, a poor understanding of how ecosystem processes evolve with age, and because of a lack of forest age data with which to initialize models. Here we present a globally gridded forest age distribution dataset that is derived from National Forest Inventory data and from satellite-derived disturbance frequencies. This gridded dataset is developed at 0.5° spatial resolution at the plant functional types classification level, one that is commonly used in dynamic global vegetation models. We find large national-scale differences in forest age distributions, for example, with a peak age-area for young forests in China, and more mature forests across Canada and in Russia. Comparing simulated forest carbon stocks and fluxes from three DGVM models (LPJ, ORCHIDEE, and ORCHIDEE-Forest Management) with a global forest database, we illustrate the importance of accounting for structural development as forests develop. With over half the world's forests modified by human activities, or influenced by natural disturbance, spatial patterns of forest age distributions are a necessary feature of forward models for closing the global carbon budget within a consistent modeling framework.

  20. Mouse models of age-related mitochondrial neurosensory hearing loss.

    Science.gov (United States)

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  1. Aging mechanism in model Pickering emulsion

    Science.gov (United States)

    Fouilloux, Sarah; Malloggi, Florent; Daillant, Jean; Thill, Antoine

    We study the stability of a model Pickering emulsion system. A special counter-flow microfluidics set-up was used to prepare monodisperse Pickering emulsions, with oil droplets in water. The wettability of the monodisperse silica nanoparticles (NPs) could be tuned by surface grafting and the surface coverage of the droplets was controlled using the microfluidics setup. A surface coverage as low as 23$\\%$ is enough to stabilize the emulsions and we evidence a new regime of Pickering emulsion stability where the surface coverage of emulsion droplets of constant size increases in time, in coexistence with a large amount of dispersed phase. Our results demonstrate that the previously observed limited coalescence regime where surface coverage tends to control the average size of the final droplets must be put in a broader perspective.

  2. Development of a bioenergetics model for age-0 American Shad

    Science.gov (United States)

    Sauter, Sally T.

    2011-01-01

    Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur.

  3. A homologue of the yeast SHE4 gene is essential for the transition between the syncytial and cellular stages during sexual reproduction of the fungus Podospora anserina.

    Science.gov (United States)

    Berteaux-Lecellier, V; Zickler, D; Debuchy, R; Panvier-Adoutte, A; Thompson-Coffe, C; Picard, M

    1998-01-01

    The Podospora anserina cro1 gene was identified as a gene required for sexual sporulation. Crosses homozygous for the cro1-1 mutation yield fruiting bodies which produce few asci due to the formation of giant plurinucleate cells instead of dikaryotic cells after fertilization. This defect does not impair karyogamy, but meioses of the resultant polyploid nuclei are most often abortive. Cytological studies suggest that the primary defect of the mutant is its inability to form septa between the daughter nuclei after each mitosis, a step specific for normal dikaryotic cell divisions. The cro1-1 mutant would thus be unable to leave the syncytial vegetative state while abiding by the meiotic programme. cro1-1 also shows defects in ascospore germination and growth rate. GFP-tagging of the CRO1 protein reveals that it is a cytosolic protein mainly expressed at the beginning of the dikaryotic stage and at the time of ascospore maturation. The CRO1 protein exhibits significant similarity to the SHE4 protein, which is required for asymmetric mating-type switching in budding yeast cells. Thus, a gene involved in asymmetric cell divisions in a unicellular organism plays a key role at the transition between the syncytial (vegetative) state and the cellular (sexual) state in a filamentous fungus. PMID:9482722

  4. PaTrx1 and PaTrx3, two cytosolic thioredoxins of the filamentous ascomycete Podospora anserina involved in sexual development and cell degeneration.

    Science.gov (United States)

    Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

    2007-12-01

    In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development.

  5. The transcriptional response to the inactivation of the PaMpk1 and PaMpk2 MAP kinase pathways in Podospora anserina.

    Science.gov (United States)

    Bidard, Frédérique; Coppin, Evelyne; Silar, Philippe

    2012-08-01

    Transcription pattern during mycelium growth of Podospora anserina was assayed by microarray analysis in wild type and in mutants affected in the MAP kinase genes PaMpk1 and PaMpk2 and in the NADPH oxidase gene PaNox1. 15% of the genes have their expression modified by a factor two or more as growth proceeds in wild type. The genes whose expression is modified during growth in P. anserina are either not conserved or differently regulated in Neurospora crassa and Aspergillus niger, two fungi for which transcriptome data during growth are available. The P. anserina mutants display a similar alteration of their transcriptome profile, with nearly 1000 genes affected similarly in the three mutants, accounting for their similar growth phenotypes. Yet, each mutant has its specific set of modified transcripts, in line with particular phenotypes exhibited by each mutant. Again, there is limited conservation during evolution of the genes regulated at the transcription level by MAP kinases, as indicated by the comparison the P. anserina data, with those of Aspergillus fumigatus and N. crassa, two fungi for which gene expression data are available for mutants of the MAPK pathways. Among the genes regulated in wild type and affected in the mutants, those involved in carbohydrate and secondary metabolisms appear prominent. The vast majority of the genes differentially expressed are of unknown function. Availability of their transcription profile at various stages of development should help to decipher their role in fungal physiology and development.

  6. The Healthy Aging Research Network: Modeling Collaboration for Community Impact.

    Science.gov (United States)

    Belza, Basia; Altpeter, Mary; Smith, Matthew Lee; Ory, Marcia G

    2017-03-01

    As the first Centers for Disease Control and Prevention (CDC) Prevention Research Centers Program thematic network, the Healthy Aging Research Network was established to better understand the determinants of healthy aging within older adult populations, identify interventions that promote healthy aging, and assist in translating research into sustainable community-based programs throughout the nation. To achieve these goals requires concerted efforts of a collaborative network of academic, community, and public health organizational partnerships. For the 2001-2014 Prevention Research Center funding cycles, the Healthy Aging Research Network conducted prevention research and promoted the wide use of practices known to foster optimal health. Organized around components necessary for successful collaborations (i.e., governance and infrastructure, shaping focus, community involvement, and evaluation and improvement), this commentary highlights exemplars that demonstrate the Healthy Aging Research Network's unique contributions to the field. The Healthy Aging Research Network's collaboration provided a means to collectively build capacity for practice and policy, reduce fragmentation and duplication in health promotion and aging research efforts, maximize the efficient use of existing resources and generate additional resources, and ultimately, create synergies for advancing the healthy aging agenda. This collaborative model was built upon a backbone organization (coordinating center); setting of common agendas and mutually reinforcing activities; and continuous communications. Given its successes, the Healthy Aging Research Network model could be used to create new and evaluate existing thematic networks to guide the translation of research into policy and practice.

  7. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  8. An age-structured population balance model for microbial dynamics

    Directory of Open Access Journals (Sweden)

    Duarte M.V.E.

    2003-01-01

    Full Text Available This work presents an age-structured population balance model (ASPBM for a bioprocess in a continuous stirred-tank fermentor. It relates the macroscopic properties and dynamic behavior of biomass to the operational parameters and microscopic properties of cells. Population dynamics is governed by two time- and age-dependent density functions for living and dead cells, accounting for the influence of substrate and dissolved oxygen concentrations on cell division, aging and death processes. The ASPBM described biomass and substrate oscillations in aerobic continuous cultures as experimentally observed. It is noteworthy that a small data set consisting of nonsegregated measurements was sufficient to adjust a complex segregated mathematical model.

  9. Exact solution of an evolutionary model without aging

    Science.gov (United States)

    Onody, Roberto N.; de Medeiros, Nazareno G. F.

    1999-09-01

    We introduce an age-structured asexual population model containing all the relevant features of evolutionary aging theories. Beneficial as well as deleterious mutations, heredity, and arbitrary fecundity are present and managed by natural selection. An exact solution without aging is found. We show that fertility is associated with generalized forms of the Fibonacci sequence, while mutations and natural selection are merged into an integral equation which is solved by Fourier series. Average survival probabilities and Malthusian growth exponents are calculated and indicate that the system may exhibit mutational meltdown. The relevance of the model in the context of fissile reproduction groups like many protozoa and coelenterates is discussed.

  10. The heuristic value of redundancy models of aging.

    Science.gov (United States)

    Boonekamp, Jelle J; Briga, Michael; Verhulst, Simon

    2015-11-01

    Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. To this end, we explore the heuristic value of redundancy models of aging to develop a deeper insight into the mechanisms causing variation in senescence and lifespan. We start by showing (i) how different redundancy model parameters affect projected aging and mortality, and (ii) how variation in redundancy model parameters relates to variation in parameters of the Gompertz equation. Lifestyle changes or medical interventions during life can modify mortality rate, and we investigate (iii) how interventions that change specific redundancy parameters within the model affect subsequent mortality and actuarial senescence. Lastly, as an example of data-directed modelling and the insights that can be gained from this, (iv) we fit a redundancy model to mortality patterns observed by Mair et al. (2003; Science 301: 1731-1733) in Drosophila that were subjected to dietary restriction and temperature manipulations. Mair et al. found that dietary restriction instantaneously reduced mortality rate without affecting aging, while temperature manipulations had more transient effects on mortality rate and did affect aging. We show that after adjusting model parameters the redundancy model describes both effects well, and a comparison of the parameter values yields a deeper insight in the mechanisms causing these contrasting effects. We see replacement of the redundancy model parameters by more detailed sub-models of these parameters as a next step in linking demographic patterns to underlying molecular mechanisms.

  11. Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy.

    Science.gov (United States)

    Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

    2016-01-01

    This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population.

  12. Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy

    Directory of Open Access Journals (Sweden)

    Ming-Ming Lai

    2016-01-01

    Full Text Available This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96 indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population.

  13. Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy

    Science.gov (United States)

    Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

    2016-01-01

    This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population. PMID:27293889

  14. An age-structured extension to the vectorial capacity model.

    Directory of Open Access Journals (Sweden)

    Vasiliy N Novoseltsev

    Full Text Available BACKGROUND: Vectorial capacity and the basic reproductive number (R(0 have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention. METHODOLOGY/PRINCIPAL FINDINGS: Based on survival analysis we derived new equations for vectorial capacity and R(0 that are valid for any pattern of age-dependent (or age-independent vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1 lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2 encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3 provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies. CONCLUSIONS/SIGNIFICANCE: Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0 was most important when (1 vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0 is above or below 1, (2 vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3 the vector exhibits complex patterns of age-dependent mortality and R(0 ∼ 1. A limiting factor in the construction and evaluation of new age

  15. Development of a bioenergetics model for age-0 American Shad

    Science.gov (United States)

    Sauter, Sally T.

    2011-01-01

    Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur. Bioenergetics modeling is particularly useful when research questions involve multiple species and trophic levels (e.g. plankton communities). Bioenergetics models are mass-balance equations where the energy acquired from food is partitioned between maintenance costs, waste products, and growth (Winberg 1956). Specifically, the Wisconsin bioenergetics model (Hanson et al. 1997) is widely used in fisheries science. Researchers have extensively tested, reviewed, and improved on this modeling approach for over 30 years (Petersen et al. 2008). Development of a bioenergetics model for any species requires three key components: 1) determine physiological parameters for the model through laboratory experiments or incorporate data from a closely related species, 2) corroboration of the model with growth and consumption estimates from independent research, and 3) error analysis of model parameters. Wisconsin bioenergetics models have been parameterized for many of the salmonids and

  16. Mathematically modelling the dynamics of cholesterol metabolism and ageing.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2016-07-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This condition becomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75 years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism is inextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. The aim of this work was to use mathematical modelling to explore how cholesterol metabolism is affected by the ageing process. To do this we updated a previously published whole-body mathematical model of cholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biological system. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reverse cholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of the model was explored by the use of both local and global parameter scans. In addition, acute cholesterol feeding was used to explore the effectiveness of the regulatory mechanisms which are responsible for maintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responder to cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly. The model was also used to explore the effects of ageing in tandem with three different cholesterol ester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype, conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotype reflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated the importance of CETP genotypes such as I405V, and their potential role in healthy ageing.

  17. Catastrophic senescence and semelparity in the Penna aging model

    CERN Document Server

    Pinol, C M N

    2010-01-01

    The catastrophic senescence of the Pacific salmon is among the initial tests used to validate the Penna aging model. Based on the mutation accumulation theory, the sudden decrease in fitness following reproduction may be solely attributed to the semelparity of the species. In this work, we report other consequences of mutation accumulation. Contrary to earlier findings, such dramatic manifestation of aging depends not only on the choice of breeding strategy but also on the value of the reproduction age, R, and the mutation threshold, T. Senescence is catastrophic when T\\leq R. As the organism's tolerance for harmful genetic mutations increases, the aging process becomes more gradual. We observe senescence that is threshold dependent whenever T>R. That is, the sudden drop in survival rate occurs at age equal to the mutation threshold value.

  18. Positive explorers: modeling dynamic control in normal aging.

    Science.gov (United States)

    Glass, Brian D; Osman, Magda

    2017-01-01

    Situations in which there are multiple changes occurring all at once and which demand complex decisions to be made are common throughout life, but little is known about how normal aging influences performance on these types of scenarios. To determine performance differences associated with normal aging, we test older and younger adults in a dynamic control task. The task involves the control of a single output variable over time via multiple and uncertain input controls. The Single Limited Input, Dynamic Exploratory Responses (SLIDER) computational model, is implemented to determine the behavioral characteristics associated with normal aging in a dynamic control task. Model-based analysis demonstrates a unique performance signature profile associated with normal aging. Specifically, older adults exhibit a positivity effect in which they are more influenced by positively valenced feedback, congruent with previous research, as well as enhanced exploratory behavior.

  19. Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models

    OpenAIRE

    2012-01-01

    Aging is a complex and inevitable biological process that is associated with numerous chronically debilitating health effects. Development of effective interventions for promoting healthy aging is an active but challenging area of research. Mechanistic studies in various model organisms, noticeably two invertebrates, Caenorhabditis elegans and Drosophila melanogaster, have identified many genes and pathways as well as dietary interventions that modulate lifespan and healthspan. These studies ...

  20. Age constraints and fine tuning in VAMP models

    CERN Document Server

    Franca, U; Franca, Urbano; Rosenfeld, Rogerio

    2004-01-01

    VAMP (VAriable-Mass Particles) scenarios, in which the mass of the cold dark matter particles is a function of the scalar field responsible for the present acceleration of the universe, have been proposed as a solution to the cosmic coincidence problem, since in the attractor regime both dark energy and dark matter scale in the same way. We have calculated the age of the universe for an ensemble of models in this scenario obtaining $t_0 = 15.2^{+1.1}_{-0.8}$ Gyr, which is in poor agreement with the recent results obtained by the WMAP satellite. We show that observational constraints, particularly the age of the universe, require a strong fine tuning in the model. We conclude that VAMP models have difficulties to simultaneously account for the observed age of the universe and the current value of the dark energy equation of state.

  1. Porosity estimation of aged mortar using a micromechanical model.

    Science.gov (United States)

    Hernández, M G; Anaya, J J; Sanchez, T; Segura, I

    2006-12-22

    Degradation of concrete structures located in high humidity atmospheres or under flowing water is a very important problem. In this study, a method for ultrasonic non-destructive characterization in aged mortar is presented. The proposed method makes a prediction of the behaviour of aged mortar accomplished with a three phase micromechanical model using ultrasonic measurements. Aging mortar was accelerated by immersing the probes in ammonium nitrate solution. Both destructive and non-destructive characterization of mortar was performed. Destructive tests of porosity were performed using a vacuum saturation method and non-destructive characterization was carried out using ultrasonic velocities. Aging experiments show that mortar degradation not only involves a porosity increase, but also microstructural changes in the cement matrix. Experimental results show that the estimated porosity using the proposed non-destructive methodology had a comparable performance to classical destructive techniques.

  2. Modified DM Models for Aging Networks Based on Neighborhood Connectivity

    Institute of Scientific and Technical Information of China (English)

    WEI Du-Qu; LIN Min; LUO Xiao-Shu; WANG Gang; ZOU Yan-Li; CHEN Tian-Lun

    2008-01-01

    Two modified Dorogovtsev-Mendes (DM) models of aging networks based on the dynamics of connecting nearest-neighbors are introduced. One edge of the new site is connected to the old site with probabilityekt-αas in the DM's model, where the degree and age of the old site are k and t, respectively. We consider two eases, I.e. The other edges of the new site attaching to the nearest-neighbors of the old site with uniform and degree connectivity probability, respectively. The network structure changes with an increase of aging exponent α. It is found that the networks can produce scale-free degree distributions with small-world properties. And the different connectivity probabilities lead to the different properties of the networks.

  3. An R package for fitting age, period and cohort models

    Directory of Open Access Journals (Sweden)

    Adriano Decarli

    2014-11-01

    Full Text Available In this paper we present the R implementation of a GLIM macro which fits age-period-cohort model following Osmond and Gardner. In addition to the estimates of the corresponding model, owing to the programming capability of R as an object oriented language, methods for printing, plotting and summarizing the results are provided. Furthermore, the researcher has fully access to the output of the main function (apc which returns all the models fitted within the function. It is so possible to critically evaluate the goodness of fit of the resulting model.

  4. Rank-based deactivation model for networks with age

    Institute of Scientific and Technical Information of China (English)

    Wang Xue-Wen; Yang Guo-Hong; Li Xiao-Lin; Xu Xin-Jian

    2013-01-01

    We study the impact of age on network evolution which couples addition of new nodes and deactivation of old ones.During evolution,each node experiences two stages:active and inactive.The transition from the active state to the inactive one is based on the rank of the node.In this paper,we adopt age as a criterion of ranking,and propose two deactivation models that generalize previous research.In model A,the older active node possesses the higher rank,whereas in model B,the younger active node takes the higher rank.We make a comparative study between the two models through the node-degree distribution.

  5. A meta-analytic review of emotion recognition and aging: implications for neuropsychological models of aging.

    Science.gov (United States)

    Ruffman, Ted; Henry, Julie D; Livingstone, Vicki; Phillips, Louise H

    2008-01-01

    This meta-analysis of 28 data sets (N=705 older adults, N=962 younger adults) examined age differences in emotion recognition across four modalities: faces, voices, bodies/contexts, and matching of faces to voices. The results indicate that older adults have increased difficulty recognising at least some of the basic emotions (anger, sadness, fear, disgust, surprise, happiness) in each modality, with some emotions (anger and sadness) and some modalities (face-voice matching) creating particular difficulties. The predominant pattern across all emotions and modalities was of age-related decline with the exception that there was a trend for older adults to be better than young adults at recognising disgusted facial expressions. These age-related changes are examined in the context of three theoretical perspectives-positivity effects, general cognitive decline, and more specific neuropsychological change in the social brain. We argue that the pattern of age-related change observed is most consistent with a neuropsychological model of adult aging stemming from changes in frontal and temporal volume, and/or changes in neurotransmitters.

  6. Modeling load-induced aging of loudspeaker suspension

    OpenAIRE

    KLIPPEL, Wolfgang

    2012-01-01

    International audience; The mechanical suspension becomes more and more compliant over time changing the loudspeaker properties (e.g. resonance frequency) significantly. This aging process is reproducible and the decay of the stiffness can be modeled by accumulating the apparent power supplied to the suspension part and using an exponential relationship. The free parameters of this model are estimated from empirical data provided by on-line monitoring or intermittent measurements during regul...

  7. SIR epidemic models with age structure and immigration

    OpenAIRE

    Franceschetti, Andrea

    2006-01-01

    The aim of the present work is to discuss some aspects about a problem of epidemiological modeling, the evolution of a childhood infectious disease in a human population subject to immigration and in which age-strucure is taken into account.

  8. Mathematical Modelling and Experimental Analysis of Early Age Concrete

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, Anders Boe

    1997-01-01

    The report deals with mathematical models for concrete at early age. In the hardening process chemical reactions take place and the concrete skeleton is created. The processes changes the moisture content and produces heat. The associated temperature rise gives expansion of the material which may...

  9. Revisiting dark energy models using differential ages of galaxies

    Science.gov (United States)

    Rani, Nisha; Jain, Deepak; Mahajan, Shobhit; Mukherjee, Amitabha; Biesiada, Marek

    2017-03-01

    In this work, we use a test based on the differential ages of galaxies for distinguishing the dark energy models. As proposed by Jimenez and Loeb in [1], relative ages of galaxies can be used to put constraints on various cosmological parameters. In the same vein, we reconstruct H0dt/dz and its derivative (H0d2t/dz2) using a model independent technique called non-parametric smoothing. Basically, dt/dz is the change in the age of the object as a function of redshift which is directly linked with the Hubble parameter. Hence for reconstruction of this quantity, we use the most recent H(z) data. Further, we calculate H0dt/dz and its derivative for several models like Phantom, Einstein de Sitter (EdS), ΛCDM, Chevallier-Polarski-Linder (CPL) parametrization, Jassal-Bagla-Padmanabhan (JBP) parametrization and Feng-Shen-Li-Li (FSLL) parametrization. We check the consistency of these models with the results of reconstruction obtained in a model independent way from the data. It is observed that H0dt/dz as a tool is not able to distinguish between the ΛCDM, CPL, JBP and FSLL parametrizations but, as expected, EdS and Phantom models show noticeable deviation from the reconstructed results. Further, the derivative of H0dt/dz for various dark energy models is more sensitive at low redshift. It is found that the FSLL model is not consistent with the reconstructed results, however, the ΛCDM model is in concordance with the 3σ region of the reconstruction at redshift z>= 0.3.

  10. Anomalous scaling in an age-dependent branching model.

    Science.gov (United States)

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  11. [MEDICAL SOCIAL MODELING TECHNOLOGIES FOR ACTIVE AGING IN KAZAKHSTAN].

    Science.gov (United States)

    Benberin, V V; Akhetov, A A; Tanbaeva, G Z

    2015-01-01

    The article discusses a new model for active ageing in Republic of Kazakhstan with participation the state, population and medical social services. Achieving active longevity will lead to positive trends in the development of human capital of the state, because it enables to use experience and knowledge of senior generation in enhancing the effectiveness of socio-economic transformation in health care. The study was carried out on the base of the Central clinical hospital of the President's affairs administration in Republic of Kazakhstan, with the participation of 147 admitted patients of elderly and senile age.

  12. Modeling Manufacturing Impacts on Aging and Reliability of Polyurethane Foams

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Rekha R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Roberts, Christine Cardinal [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mondy, Lisa Ann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Soehnel, Melissa Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Johnson, Kyle [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lorenzo, Henry T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-09-25

    Polyurethane is a complex multiphase material that evolves from a viscous liquid to a system of percolating bubbles, which are created via a CO2 generating reaction. The continuous phase polymerizes to a solid during the foaming process generating heat. Foams introduced into a mold increase their volume up to tenfold, and the dynamics of the expansion process may lead to voids and will produce gradients in density and degree of polymerization. These inhomogeneities can lead to structural stability issues upon aging. For instance, structural components in weapon systems have been shown to change shape as they age depending on their molding history, which can threaten critical tolerances. The purpose of this project is to develop a Cradle-to-Grave multiphysics model, which allows us to predict the material properties of foam from its birth through aging in the stockpile, where its dimensional stability is important.

  13. Modeling Manufacturing Impacts on Aging and Reliability of Polyurethane Foams

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Rekha R.; Roberts, Christine Cardinal; Mondy, Lisa Ann; Soehnel, Melissa Marie; Johnson, Kyle; Lorenzo, Henry T.

    2016-10-01

    Polyurethane is a complex multiphase material that evolves from a viscous liquid to a system of percolating bubbles, which are created via a CO2 generating reaction. The continuous phase polymerizes to a solid during the foaming process generating heat. Foams introduced into a mold increase their volume up to tenfold, and the dynamics of the expansion process may lead to voids and will produce gradients in density and degree of polymerization. These inhomogeneities can lead to structural stability issues upon aging. For instance, structural components in weapon systems have been shown to change shape as they age depending on their molding history, which can threaten critical tolerances. The purpose of this project is to develop a Cradle-to-Grave multiphysics model, which allows us to predict the material properties of foam from its birth through aging in the stockpile, where its dimensional stability is important.

  14. Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss; Juul, Jeppe Søgaard; Trusina, Ala

    2012-01-01

    DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn...... to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity. Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity...... of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders...

  15. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  16. Automatic age and gender classification using supervised appearance model

    Science.gov (United States)

    Bukar, Ali Maina; Ugail, Hassan; Connah, David

    2016-11-01

    Age and gender classification are two important problems that recently gained popularity in the research community, due to their wide range of applications. Research has shown that both age and gender information are encoded in the face shape and texture, hence the active appearance model (AAM), a statistical model that captures shape and texture variations, has been one of the most widely used feature extraction techniques for the aforementioned problems. However, AAM suffers from some drawbacks, especially when used for classification. This is primarily because principal component analysis (PCA), which is at the core of the model, works in an unsupervised manner, i.e., PCA dimensionality reduction does not take into account how the predictor variables relate to the response (class labels). Rather, it explores only the underlying structure of the predictor variables, thus, it is no surprise if PCA discards valuable parts of the data that represent discriminatory features. Toward this end, we propose a supervised appearance model (sAM) that improves on AAM by replacing PCA with partial least-squares regression. This feature extraction technique is then used for the problems of age and gender classification. Our experiments show that sAM has better predictive power than the conventional AAM.

  17. Network model of human aging: Frailty limits and information measures

    Science.gov (United States)

    Farrell, Spencer G.; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-11-01

    Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmaxcomputationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q topology of aging populations.

  18. Spectral age modelling of the `Sausage' cluster radio relic

    Science.gov (United States)

    Stroe, Andra; Harwood, Jeremy J.; Hardcastle, Martin J.; Röttgering, Huub J. A.

    2014-12-01

    CIZA J2242.8+5301 is a post-core passage, binary merging cluster that hosts a large, thin, arc-like radio relic, nicknamed the `Sausage', tracing a relatively strong shock front. We perform spatially resolved spectral fitting to the available radio data for this radio relic, using a variety of spectral ageing models, with the aim of finding a consistent set of parameters for the shock and radio plasma. We determine an injection index of 0.77^{+0.03}_{-0.02} for the relic plasma, significantly steeper than was found before. Standard particle acceleration at the shock front implies a Mach number M=2.90^{+0.10}_{-0.13}, which now matches X-ray measurements. The shock advance speed is vshock ≈ 2500 km s-1, which places the core passage of the two subclusters 0.6-0.8 Gyr ago. We find a systematic spectral age increase from 0 at the northern side of the relic up to ˜60 Myr at ˜145 kpc into the downstream area, assuming a 0.6 nT magnetic field. Under the assumption of freely ageing electrons after acceleration by the `Sausage' shock, the spectral ages are hard to reconcile with the shock speed derived from X-ray and radio observations. Re-acceleration or unusually efficient transport of particle in the downstream area and line-of-sight mixing could help explain the systematically low spectral ages.

  19. SIVS EPIDEMIC MODELS WITH INFECTION AGE AND NONLINEAR VACCINATION RATE

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Vaccination is a very important strategy for the elimination of infectious diseaVaccination is a very important strategy for the elimination of infectious diseases. A SIVS epidemic model with infection age and nonlinear vaccination has been formulated in this paper. Using the theory of differential and integral equation, we show the local asymptotic stability of the infection-free equilibrium and the endemic equilibrium under some assumptions.

  20. Anomalous scaling in an age-dependent branching model

    OpenAIRE

    Keller-Schmidt, Stephanie; Tugrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-01-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age $\\tau$ as $\\tau^{-\\alpha}$. Depending on the exponent $\\alpha$, the scaling of tree depth with tree size $n$ displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition ($\\alpha=1$) tree depth grows as $(\\log n)^2$. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus p...

  1. The Age-Competency Model to the Study of the Age-Wage Profiles for Workers

    CERN Document Server

    Maximov, S I

    2005-01-01

    In this article, I present a new approach and a novel model to the study of the life cycle of wages. The key idea is that wage can be thought as remuneration paid for the competency. It is assumed with the approach that there are three mechanisms acting at micro level and resulting in the change of workers' competencies during their lives. These are an endogenous growth of workers' initial competencies; a rate of investments in schooling in the life cycle of wages; and an effect of relative losses in workers' competencies. The developed model is to shed light on the processes resulting in the age-wage profiles seen in mass. The model obeys a nonlinear integro-differential equation. The found analytic solution of the equation has the form of Fisk PDF of a special type. The solution and its features are discussed. The regression technique is used to check the model upon reliability. The model provides better fitting to the data (Elo and Salonen, 2004) than minceraninan earnings function (Mincer, 1974) does.

  2. Age structured dynamical model for an endangered lizard Eulamprus leuraensis

    Science.gov (United States)

    Supriatna, A. K.; Rachmadani, Q.; Ilahi, F.; Anggriani, N.; Nuraini, N.

    2014-02-01

    The Blue Mountains Water Skink, Eulamprus leuraensis, is listed as an endangered species under the IUCN Red List. This lizard species has a typical characteristic of growth with a low fecundity. It is known that the offspring quality may decline with maternal age of the parents despite they can grow rapidly from neonatal size to adult size within two to three years. It is also believed that low adult survival rates and specialization on rare and fragmented type of habitat are the main cause leading to the endangered status of the lizard. A mathematical model with age structure for Eulamprus leuraensis, taking into account the variation of survival rate in each structure and the declining of offspring quality with respect to maternal age is considered here. Stable coexistence of non-trivial equilibriumis shown. It is also shown that an endangered status is due to combination oflow reproductive output and low rates of adult survival. Further, understanding the age structure within populations can facilitate efective management of the endangered species.

  3. Self-Organization of Aging in a Modified Penna Model

    Science.gov (United States)

    Kim, Gi Ok; Shim, Sugie

    The Penna model for biological aging is modified so that the fertility of each individual is determined by means of the number of activated mutations at that time. A new concept of "good" mutation, which makes an individual to mature enough to reproduce, is introduced. It is assumed that each individual can reproduce only during adulthood, which is determined by the number of activated mutations. The results of Monte Carlo calculations using the modified model show that the ranges of the reproductive age are broadened as time goes by, thus showing self-organization in the biological aging to the direction of the maximum self-conservation. In addition, the population, the survival rate, and the average life span were calculated and analyzed by changing the number of new mutations at birth. It is observed that the higher is the considered number of new mutations at birth, the shorter is the obtained average life span. The mortality functions are also calculated and they showed the exponential increase in adulthood, satisfying the Gompertz law.

  4. Re-evaluating neonatal-age models for ungulates: Does model choice affect survival estimates?

    Science.gov (United States)

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  5. StalAge - A new algorithm especially designed for the construction of speleothem age-depth models

    Science.gov (United States)

    Scholz, Denis; Hoffmann, Dirk

    2010-05-01

    A standard approach to construct age-depth models for speleothems on the basis of 230Th/U-ages is not available yet. Some studies apply linear interpolation between dated depths; others use least squares polynomial fits. Other authors, in turn, use various kinds of splines or even more sophisticated methods based on the general growth mechanisms of speleothems. A general approach to estimate the uncertainty of stalagmite age models has neither been developed yet. Since the exact determination of the timing and duration of climatic events recorded in speleothem calcite depends on the method used to calculate the age model, a general technique for the calculation of both the age model and its uncertainty is urgently needed. Here we present a new algorithm, especially designed for constructing age-depth models based on speleothem 230Th/U-ages. The algorithm relies on two basic assumptions: (i) the age model must increase monotonically with increasing distance from top of the stalagmite, and (ii) if possible within the associated error bars, the simplest age-depth relationship (i.e., a straight line) is fitted to the age data. Whereas the first assumption simply arises from the absolute constraint of increasing age with increasing distance from top, the second assumption avoids over-interpretation of the age data. The performance of the algorithm was tested using synthetic speleothem age data. For this purpose, a numerical model simulating (i) speleothem growth, (ii) incorporation and temporal evolution of U-series isotopes and (iii) mass spectrometric analysis was developed. This allows simulation of extreme scenarios, such as stalagmite sections including obvious outliers, age inversions and pronounced detrital contamination, and also to test the performance and robustness of the algorithm under these conditions. The developed algorithm has distinct advantages in comparison with the existing methods. Firstly, it is very robust. Outliers and age inversions are

  6. AGING PERFORMANCE OF MODEL 9975 PACKAGE FLUOROELASTOMER O-RINGS

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, E.; Daugherty, W.; Skidmore, E.; Dunn, K.; Fisher, D.

    2011-05-31

    The influence of temperature and radiation on Viton{reg_sign} GLT and GLT-S fluoroelastomer O-rings is an ongoing research focus at the Savannah River National Laboratory. The O-rings are credited for leaktight containment in the Model 9975 shipping package used for transportation of plutonium-bearing materials. At the Savannah River Site, the Model 9975 packages are being used for interim storage. Primary research efforts have focused on surveillance of O-rings from actual packages, leak testing of seals at bounding aging conditions and the effect of aging temperature on compression stress relaxation behavior, with the goal of service life prediction for long-term storage conditions. Recently, an additional effort to evaluate the effect of aging temperature on the oxidation of the materials has begun. Degradation in the mechanical properties of elastomers is directly related to the oxidation of the polymer. Sensitive measurements of the oxidation rate can be performed in a more timely manner than waiting for a measurable change in mechanical properties, especially at service temperatures. Measuring the oxidation rate therefore provides a means to validate the assumption that the degradation mechanisms(s) do not change from the elevated temperatures used for accelerated aging and the lower service temperatures. Monitoring the amount of oxygen uptake by the material over time at various temperatures can provide increased confidence in lifetime predictions. Preliminary oxygen consumption analysis of a Viton GLT-based fluoroelastomer compound (Parker V0835-75) using an Oxzilla II differential oxygen analyzer in the temperature range of 40-120 C was performed. Early data suggests oxygen consumption rates may level off within the first 100,000 hours (10-12 years) at 40 C and that sharp changes in the degradation mechanism (stress-relaxation) are not expected over the temperature range examined. This is consistent with the known long-term heat aging resistance of

  7. Test of magnetic susceptibility and grain-size age models of loess

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ages of the stratigraphic boundary MIS1/2 and MIS3/4 of the Yuanbu loess section in Linxia are used as the basis of the nodal control age. The age of MIS1/2 and MIS3/4 are obtained from the latest international research result-the climatic events recorded in the stalagmite in the Hulu Cave in Nanjing, that MIS1/2 is 11.5 kaB. P. and MIS3/4 is 59.8 kaB.P.. The ages of the two climatic events contain three nodal age control models (Model 1: 0 kaB. P. -59.8 kaB. P.; Model 2: 0 kaB. P. -11.5 kaB. P. and 11.5kaB. P. -59.8 kaB. P.; Model 3: 11.5 kaB. P. -59.8 kaB. P. ), which are used as the nodal control age separately. The deposition times of various stratigraphic horizons are calculated by using the magnetic susceptibility age model and grain-size age model, and then compared with each other. In addition, the AMS14C age, OSL age and the ages of YD and H events are compared with the ages of the corresponding horizons calculated by the three models of nodal control ages. From the analyses of lithologic characters and climatic stages it has been found that both the magnetic susceptibility age model and the grain-size age model have some defects. Because the accurate control ages are selected as the nodal points of the glacial period or interglacial period, the stratigraphic deposition times determined by the high resolution of magnetic susceptibility age model and grain-size age model approximate to the actual ages. As for the relative accuracy of the two age models, the magnetic susceptibility age model is more accurate than the grain-size age model.

  8. Spectral Aging Model Applied to Meteosat First Generation Visible Band

    Directory of Open Access Journals (Sweden)

    Ilse Decoster

    2014-03-01

    Full Text Available The Meteosat satellites have been operational since the early eighties, creating so far a continuous time period of observations of more than 30 years. In order to use this data for climate data records, a consistent calibration is necessary between the consecutive instruments. Studies have shown that the Meteosat First Generation (MFG satellites (1982–2006 suffer from in-flight degradation which is spectral of nature and is not corrected by the official calibration of EUMETSAT. Continuing on previous published work by the same authors, this paper applies the spectral aging model to a set of clear-sky and cloudy targets, and derives the model parameters for all six MFG satellites (Meteosat-2 to -7. Several problems have been encountered, both due to the instrument and due to geophysical occurrences, and these are discussed and illustrated here in detail. The paper shows how the spectral aging model is an improvement compared to the EUMETSAT calibration method with a stability of 1%–2% for Meteosat-4 to -7, which increases up to 6% for ocean sites using the full MFG time period.

  9. Hybrid Aging Delay Model Considering the PBTI and TDDB

    Institute of Scientific and Technical Information of China (English)

    Yong Miao; Mao-Xiang Yi; Gui-Mao Zhang; Da-Wen Xu

    2015-01-01

    Abstract-With a 45nm process technique, the shrinking silicon feature size brings in a high-k/metal gate which significantly exacerbates the positive bias temperature instability (PBTI) and time-dependent dielectric breakdown (TDDB) effects of a NMOS transistor. However, previous works presented delay models to characterize the PBTI or TDDB individually. This paper demonstrates that the delay caused by the joint effects of PBTI and TDDB widely differs from the cumulated result of the delay caused by the PBTI and TDDB, respectively, with the experiments on an inverter chain. This paper proposes a hybrid aging delay model comprising both the PBTI and TDDB effects by analyzing the relationship between the aging propagation delay and the inherent delay of the gate. Experimental results on the logic gates under 45nm, 32 nm, 22nm, and 16nm CMOS technologies show that the maximum error between the proposed model and the actual value is less than 2.5%, meanwhile the average error is about 1.5%.

  10. Cognitive aging and hearing acuity: modeling spoken language comprehension.

    Science.gov (United States)

    Wingfield, Arthur; Amichetti, Nicole M; Lash, Amanda

    2015-01-01

    The comprehension of spoken language has been characterized by a number of "local" theories that have focused on specific aspects of the task: models of word recognition, models of selective attention, accounts of thematic role assignment at the sentence level, and so forth. The ease of language understanding (ELU) model (Rönnberg et al., 2013) stands as one of the few attempts to offer a fully encompassing framework for language understanding. In this paper we discuss interactions between perceptual, linguistic, and cognitive factors in spoken language understanding. Central to our presentation is an examination of aspects of the ELU model that apply especially to spoken language comprehension in adult aging, where speed of processing, working memory capacity, and hearing acuity are often compromised. We discuss, in relation to the ELU model, conceptions of working memory and its capacity limitations, the use of linguistic context to aid in speech recognition and the importance of inhibitory control, and language comprehension at the sentence level. Throughout this paper we offer a constructive look at the ELU model; where it is strong and where there are gaps to be filled.

  11. The OMS3 JGrass-NewAge Environmental Modelling System

    Science.gov (United States)

    Formetta, G.; David, O.; Rigon, R.

    2012-12-01

    The need for integrated analysis, and the multiplicity of possible goals in analyses that require hydro-biophysical modelling, necessitates more than ever the capability of composing modelling solutions with parts of known quality, which are transparent to users and consist of reusable model components. Moreover, modern hydrological modelling requires interaction with GIS tools to allow visualizations and the data-processing necessary to synthesise knowledge from high volumes of inputs and outputs data. Last but not least, doing science that is reproducible has requirements that go beyond the computational issues to embrace the possibility to inspection the tools, and easy compare modelling solutions by third party groups. The JGrass-NewAge system was born in order to satisfy these requirements. It is based on the geographic information system uDig-JGrass, and is composed of two parts: (i) the system of visualization of the data and of the results based on uDig; (ii) the modelling components. The latter are implemented as OMS3 components which can be connected or excluded at runtime, according to the needs and works seamlessly inside the uDig Spatial Toolbox. The system is based on a hillslope-link geometrical partition of the landscape, thus the basic unit, where the water budget is evaluated, is the hillslope, and each one of them drains into a single associated link rather than cells or pixels. To this conceptual partition corresponds an implementation of informatics that uses vectorial features for channels, and raster data for hillslopes. The mass budget for each hillslope can be performed in two ways: according to a modification of Duffy dynamical model of hillslope runoff or according to HyMod lumped model. Differently from traditional rainfall-runoff models where the discharge is usually given at the outlet of a catchment, the discharge is evaluated in each link of the river network according to a procedure presented in Cuencas model. The system includes

  12. Aging and associative recognition: A view from the DRYAD model of age-related memory deficits.

    Science.gov (United States)

    Benjamin, Aaron S

    2016-02-01

    How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart.

  13. Constraints on Pacific midplate swells from global depth-age and heat flow-age models

    Science.gov (United States)

    Stein, Carol A.; Stein, Seth

    Oceanic midplate swells are identified by shallow seafloor depths. In turn, models of the processes giving rise to these regions rely on assessments of how their depths, surface heat flow, and flexural properties differ from those for lithosphere which is presumed not to have been affected by these processes. Such comparisons have been inhibited because reference thermal models, which are assumed to describe unperturbed lithosphere, predict deeper depths and lower heat flow than typically observed for lithosphere older than 70 Ma. As a result, both depth and heat flow anomalies can be overestimated. To address this difficulty, we have derived model GDH1 (Global Depth and Heat flow) by joint fitting of heat flow and bathymetry. GDH1, which has a hotter and thinner lithosphere than previous models, fits the depth and heat flow data significantly better, including the data from older lithosphere previously treated as anomalous. It also provides an improved fit to depth-to-basement data for ocean drilling sites, and to geoid offsets across fracture zones. The improved fit occurs for depth-age data from both the DBDB-5 digital bathymetry, and from regional medians from ship tracks, which yield comparable depth-age curves. We use GDH1 to study three classes of midplate swells: the Hawaiian and other hot spot swells, the Darwin Rise area of widespread Cretaceous volcanism, and the Superswell, considered a present analogue to the Darwin Rise. Heat flow on the Hawaiian swell, though anomalously high with respect to previous reference models, is at most slightly high relative to GDH1. The situation is similar for the Bermuda, Cape Verde, and Crozet hot spots. The absence of a significant heat flow anomaly favors a primarily dynamic, rather than thermal, origin for these swells. Similarly, the present depths and heat flow for the Darwin Rise are consistent with GDH1, although they were anomalous with respect to previous reference models. The depth and heat flow data thus

  14. Age-aware solder performance models : level 2 milestone completion.

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, Michael K.; Vianco, Paul Thomas; Neidigk, Matthew Aaron; Holm, Elizabeth Ann

    2010-09-01

    Legislated requirements and industry standards are replacing eutectic lead-tin (Pb-Sn) solders with lead-free (Pb-free) solders in future component designs and in replacements and retrofits. Since Pb-free solders have not yet seen service for long periods, their long-term behavior is poorly characterized. Because understanding the reliability of Pb-free solders is critical to supporting the next generation of circuit board designs, it is imperative that we develop, validate and exercise a solder lifetime model that can capture the thermomechanical response of Pb-free solder joints in stockpile components. To this end, an ASC Level 2 milestone was identified for fiscal year 2010: Milestone 3605: Utilize experimentally validated constitutive model for lead-free solder to simulate aging and reliability of solder joints in stockpile components. This report documents the completion of this milestone, including evidence that the milestone completion criteria were met and a summary of the milestone Program Review.

  15. Lattice percolation approach to 3D modeling of tissue aging

    Science.gov (United States)

    Gorshkov, Vyacheslav; Privman, Vladimir; Libert, Sergiy

    2016-11-01

    We describe a 3D percolation-type approach to modeling of the processes of aging and certain other properties of tissues analyzed as systems consisting of interacting cells. Lattice sites are designated as regular (healthy) cells, senescent cells, or vacancies left by dead (apoptotic) cells. The system is then studied dynamically with the ongoing processes including regular cell dividing to fill vacant sites, healthy cells becoming senescent or dying, and senescent cells dying. Statistical-mechanics description can provide patterns of time dependence and snapshots of morphological system properties. The developed theoretical modeling approach is found not only to corroborate recent experimental findings that inhibition of senescence can lead to extended lifespan, but also to confirm that, unlike 2D, in 3D senescent cells can contribute to tissue's connectivity/mechanical stability. The latter effect occurs by senescent cells forming the second infinite cluster in the regime when the regular (healthy) cell's infinite cluster still exists.

  16. Modeling Active Aging and Explicit Memory: An Empirical Study.

    Science.gov (United States)

    Ponce de León, Laura Ponce; Lévy, Jean Pierre; Fernández, Tomás; Ballesteros, Soledad

    2015-08-01

    The rapid growth of the population of older adults and their concomitant psychological status and health needs have captured the attention of researchers and health professionals. To help fill the void of literature available to social workers interested in mental health promotion and aging, the authors provide a model for active aging that uses psychosocial variables. Structural equation modeling was used to examine the relationships among the latent variables of the state of explicit memory, the perception of social resources, depression, and the perception of quality of life in a sample of 184 older adults. The results suggest that explicit memory is not a direct indicator of the perception of quality of life, but it could be considered an indirect indicator as it is positively correlated with perception of social resources and negatively correlated with depression. These last two variables influenced the perception of quality of life directly, the former positively and the latter negatively. The main outcome suggests that the perception of social support improves explicit memory and quality of life and reduces depression in active older adults. The findings also suggest that gerontological professionals should design memory training programs, improve available social resources, and offer environments with opportunities to exercise memory.

  17. Black carbon ageing in the Canadian Centre for Climate modelling and analysis atmospheric general circulation model

    Directory of Open Access Journals (Sweden)

    B. Croft

    2005-01-01

    Full Text Available Black carbon (BC particles in the atmosphere have important impacts on climate. The amount of BC in the atmosphere must be carefully quantified to allow evaluation of the climate effects of this type of aerosol. In this study, we present the treatment of BC aerosol in the developmental version of the 4th generation Canadian Centre for Climate modelling and analysis (CCCma atmospheric general circulation model (AGCM. The focus of this work is on the conversion of insoluble BC to soluble/mixed BC by physical and chemical ageing. Physical processes include the condensation of sulphuric and nitric acid onto the BC aerosol, and coagulation with more soluble aerosols such as sulphates and nitrates. Chemical processes that may age the BC aerosol include the oxidation of organic coatings by ozone. Four separate parameterizations of the ageing process are compared to a control simulation that assumes no ageing occurs. These simulations use 1 an exponential decay with a fixed 24h half-life, 2 a condensation and coagulation scheme, 3 an oxidative scheme, and 4 a linear combination of the latter two ageing treatments. Global BC burdens are 2.15, 0.15, 0.11, 0.21, and 0.11TgC for the control run, and four ageing schemes, respectively. The BC lifetimes are 98.1, 6.6, 5.0, 9.5, and 4.9 days, respectively. The sensitivity of modelled BC burdens, and concentrations to the factor of two uncertainty in the emissions inventory is shown to be greater than the sensitivity to the parameterization used to represent the BC ageing, except for the oxidation based parameterization. A computationally efficient parameterization that represents the processes of condensation, coagulation, and oxidation is shown to simulate BC ageing well in the CCCma AGCM. As opposed to the globally fixed ageing time scale, this treatment of BC ageing is responsive to varying atmospheric composition.

  18. Spectral age modelling of the `Sausage' cluster radio relic

    CERN Document Server

    Stroe, Andra; Hardcastle, Martin J; Röttgering, Huub J A

    2014-01-01

    CIZA J2242.8+5301 is a post-core passage, binary merging cluster that hosts a large, thin, arc-like radio relic, nicknamed the `Sausage', tracing a relatively strong shock front. We perform spatially-resolved spectral fitting to the available radio data for this radio relic, using a variety of spectral ageing models, with the aim of finding a consistent set of parameters for the shock and radio plasma. We determine an injection index of $0.77^{+0.03}_{-0.02}$ for the relic plasma, significantly steeper than was found before. Standard particle acceleration at the shock front implies a Mach number $M=2.90^{+0.10}_{-0.13}$, which now matches X-ray measurements. The shock advance speed is $v_\\mathrm{shock}\\approx2500$ km s$^{-1}$, which places the core passage of the two subclusters $0.6-0.8$ Gyr ago. We find a systematic spectral age increase from $0$ at the northern side of the relic up to $\\sim60$ Myr at $\\sim145$ kpc into the downstream area, assuming a $0.6$ nT magnetic field. Under the assumption of freely-...

  19. Acrylamide induces accelerated endothelial aging in a human cell model.

    Science.gov (United States)

    Sellier, Cyril; Boulanger, Eric; Maladry, François; Tessier, Frédéric J; Lorenzi, Rodrigo; Nevière, Rémi; Desreumaux, Pierre; Beuscart, Jean-Baptiste; Puisieux, François; Grossin, Nicolas

    2015-09-01

    Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) (p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging.

  20. Age-period-cohort models using smoothing splines: a generalized additive model approach.

    Science.gov (United States)

    Jiang, Bei; Carriere, Keumhee C

    2014-02-20

    Age-period-cohort (APC) models are used to analyze temporal trends in disease or mortality rates, dealing with linear dependency among associated effects of age, period, and cohort. However, the nature of sparseness in such data has severely limited the use of APC models. To deal with these practical limitations and issues, we advocate cubic smoothing splines. We show that the methods of estimable functions proposed in the framework of generalized linear models can still be considered to solve the non-identifiability problem when the model fitting is within the framework of generalized additive models with cubic smoothing splines. Through simulation studies, we evaluate the performance of the cubic smoothing splines in terms of the mean squared errors of estimable functions. Our results support the use of cubic smoothing splines for APC modeling with sparse but unaggregated data from a Lexis diagram.

  1. Aging through hierarchical coalescence in the East model

    CERN Document Server

    Faggionato, A; Roberto, C; Toninelli, C

    2010-01-01

    We rigorously analyze the low temperature non-equilibrium dynamics of the East model, a special example of a one dimensional oriented kinetically constrained particle model, when the initial distribution is different from the reversible one and for times much smaller than the global relaxation time. This setting has been intensively studied in the physics literature to analyze the slow dynamics which follows a sudden quench from the liquid to the glass phase. In the limit of zero temperature (i.e. a vanishing density of vacancies) and for initial distributions such that the vacancies form a renewal process we prove that the density of vacancies, the persistence function and the two-time autocorrelation function behave as staircase functions with several plateaux. Furthermore the two-time autocorrelation function displays an aging behavior. We also provide a sharp description of the statistics of the domain length as a function of time, a domain being the interval between two consecutive vacancies. When the in...

  2. Sensitivity analysis of the age-structured malaria transmission model

    Science.gov (United States)

    Addawe, Joel M.; Lope, Jose Ernie C.

    2012-09-01

    We propose an age-structured malaria transmission model and perform sensitivity analyses to determine the relative importance of model parameters to disease transmission. We subdivide the human population into two: preschool humans (below 5 years) and the rest of the human population (above 5 years). We then consider two sets of baseline parameters, one for areas of high transmission and the other for areas of low transmission. We compute the sensitivity indices of the reproductive number and the endemic equilibrium point with respect to the two sets of baseline parameters. Our simulations reveal that in areas of either high or low transmission, the reproductive number is most sensitive to the number of bites by a female mosquito on the rest of the human population. For areas of low transmission, we find that the equilibrium proportion of infectious pre-school humans is most sensitive to the number of bites by a female mosquito. For the rest of the human population it is most sensitive to the rate of acquiring temporary immunity. In areas of high transmission, the equilibrium proportion of infectious pre-school humans and the rest of the human population are both most sensitive to the birth rate of humans. This suggests that strategies that target the mosquito biting rate on pre-school humans and those that shortens the time in acquiring immunity can be successful in preventing the spread of malaria.

  3. Life satisfaction and age : Dealing with underidentification in age-period-cohort models

    NARCIS (Netherlands)

    de Ree, Joppe; Alessie, Rob

    2011-01-01

    Recent literature typically finds a U shaped relationship between life satisfaction and age. Age profiles, however, are not identified without forcing arbitrary restrictions on the cohort and/or time profiles. In this paper we report what can be identified about the relationship between life satisfa

  4. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    Science.gov (United States)

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  5. Does selection of mortality model make a difference in projecting population ageing?

    Directory of Open Access Journals (Sweden)

    Sergei Scherbov

    2016-01-01

    Full Text Available Background: In low mortality countries, assessing future ageing depends to a large extent on scenarios of future mortality reduction at old age. Often in population projections mortality reduction is implemented via life expectancy increases that do not specify mortality change at specific age groups. The selection of models that translate life expectancy into age-specific mortality rates may be of great importance for projecting the older age groups of future populations and indicators of ageing. Objective: We quantify how the selection of mortality models, assuming similar life expectancy scenarios, affects projected indices of population ageing. Methods: Using the cohort-component method, we project the populations of Italy, Japan, Russia, Sweden, and the USA. For each country, the given scenario of life expectancy at birth is translated into age-specific death rates by applying four alternative mortality models (variants of extrapolations of the log-mortality rates, the Brass relational model, and the Bongaarts shifting model. The models are contrasted according to their produced future age-specific mortality rates, population age composition, life expectancy at age 65, age at remaining life expectancy 15 years, and conventional and prospective old-age dependency ratios. Conclusions: We show strong differences between the alternative mortality models in terms of mortality age pattern and ageing indicators. Researchers of population ageing should be as careful about their choice of model of age patterns of future mortality as about scenarios of future life expectancy. The simultaneous extrapolation of age-specific death rates may be a better alternative to projecting life expectancy first and then deriving the age patterns of mortality in the second step.

  6. Constraining age and rate of deformation in the northern Bolivian Andes from cross sections, cooling ages, and thermokinematic modeling

    Science.gov (United States)

    McQuarrie, N.; Ehlers, T. A.; Rak, A. J.

    2015-12-01

    A critical component in assessing the viability of proposed plate tectonic or geodynamic processes in regions of convergence is the expected or predicted age and rate of deformation in the overriding plate. Commonly, age of deformation is inferred through geochronology of foreland basin and wedge-top sedimentary rocks and bedrock thermochronometer cooling signals. In Bolivia the original pulse of deformation of the fold-thrust belt is argue to be as young as 38-25 Ma based on the age of synorogenic strata or as old as 65-45 Ma due to proposed foreland basin rocks deposited in the Bolivian Altiplano. The large discrepancies in proposed age, rate and magnitude of deformation through the Bolivian Andes limit our ability to relate age and rate of shortening to internal geodynamic or external plate tectonic processes. We evaluate permissible ranges in age of initiation and rate of deformation through a forward kinematic model of the northern Bolivian fold-thrust belt. Each step of deformation accounts for isostatic loading from thrust faults and subsequent erosional of structural highs. The kinematic model predicts an evolution of flexural basins into which synorogenic sediments are deposited allowing us to fully integrate age of exhumation and deposition to age and magnitude of deformation. By assigning an age to each deformation step, we create a range of velocity vectors that are input into the thermokinematic model Pecube, which predicts thermochronometer cooling histories based on kinematics, topography, thermal parameters and shortening rates. We match the pattern of predicted ages with the across strike pattern of measured zircon fission track, apatite fission track and apatite (U-Th)/ He cooling ages. The sensitivity of modeled thermochronologic data to the age at which deformation initiates indicate that northern Bolivian EC started deforming at 50 Ma and may have begun as early as 55 Ma. The acceptable velocity envelope for the modeled section permits either a

  7. Continuous Age-Structured Model for Bovine Tuberculosis in African buffalo

    Science.gov (United States)

    Anguelov, R.; Kojouharov, H.

    2009-10-01

    The paper deals with a model of the spread of bovine tuberculosis in the buffalo population in the Kruger National Park in South Africa. The model uses continuous age structure and it is formulated in terms of partial differential equations using eight epidemiological classes (compartments). More precisely, the age density for each class at time t satisfies a one way wave equation, where the age is the space variable. The continuous age model discussed here is derived from a 2006 age groups model by P. C. Cross and W. M. Getz.

  8. Characterizing cognitive aging of associative memory in animal models.

    Science.gov (United States)

    Engle, James R; Barnes, Carol A

    2012-01-01

    An overview is provided of the simple single-cue delay and trace eyeblink conditioning paradigms as techniques to assess associative learning and memory in the aged. We highlight and focus this review on the optimization of the parameter space of eyeblink conditioning designs in the aged to avoid and control for potential confounds that may arise when studying aged mammals. The need to examine the contribution of non-associative factors that can contribute to performance outcomes is emphasized, and how age-related changes in the central nervous system as well as peripheral sensory factors can potentially bias the interpretation of the data in the aged is discussed. The way in which slight alterations of the parameter space in the delay and trace eyeblink conditioning paradigms can lead to delayed but intact conditioning, rather than impaired performance in aged animals is also discussed. Overall, the eyeblink conditioning paradigm, when optimized for the age of the animal in the study, is an elegantly simple technique for assessment of associative learning and memory. When design caveats described above are taken into account, this important type of memory, with its well-defined neural substrates, should definitely be included in cognitive assessment batteries for the aged.

  9. Characterizing cognitive aging of associative memory in animal models

    Directory of Open Access Journals (Sweden)

    James R Engle

    2012-09-01

    Full Text Available An overview is provided of the simple single-cue delay and trace eyeblink conditioning paradigms as techniques to assess associative learning and memory in the aged. We highlight and focus this review on the optimization of the parameter space of eyeblink conditioning designs in the aged to avoid and control for potential confounds that may arise when studying aged mammals. The need to examine the contribution of non-associative factors that can contribute to performance outcomes is emphasized, and how age-related changes in the central nervous system as well as peripheral sensory factors can potentially bias the interpretation of the data in the aged is discussed. The way in which slight alterations of the parameter space in the delay and trace eyeblink conditioning paradigms can lead to delayed but intact conditioning, rather than impaired performance in aged animals is also discussed. Overall, the eyeblink conditioning paradigm, when optimized for the age of the animal in the study, is an elegantly simple technique for assessment of associative learning and memory. When design caveats described above are taken into account, this important type of memory, with its well-defined neural substrates, should definitely be included in cognitive assessment batteries for the aged.

  10. Aged monkeys as a partial model for Parkinson's disease.

    Science.gov (United States)

    Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E

    2011-09-01

    Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies.

  11. GDF11 administration does not extend lifespan in a mouse model of premature aging

    Science.gov (United States)

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  12. The ageing lens and cataract: a model of normal and pathological ageing.

    Science.gov (United States)

    Michael, R; Bron, A J

    2011-04-27

    Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.

  13. Aging and Neurodegeneration: A Tangle of Models and Mechanisms

    Science.gov (United States)

    Chakrabarti, Sasanka; Mohanakumar, Kochupurackal P.

    2016-01-01

    The research on aging and age-related diseases, especially the neurodegenerative diseases, is on the fast track. However, the results have so far not been translated to actual benefit for the patients in terms of treatment or diagnosis of age-related degenerative diseases including those of the CNS. As far as the prevention of the cognitive decline during non-pathological aging is concerned, there is nothing much to offer other than calorie restriction and physical exercise. Needless to say, the benefits are not up to our expectations. However, over the years at the experimental level it has been possible to identify several cellular and molecular mechanisms that are intricately associated with aging in general and neurodegenerative diseases in particular. These include oxidative stress and altered redox-signaling, mitochondrial dysfunction, inflammation, proteotoxicity and altered gene expressions. These inter-dependent pathways mediate cellular senescence and often culminate in programmed cell death like apoptosis and autophagy, and in the context of brain these changes are manifested clinically as cognitive decline and pathologically as neurodegeneration. This special issue provides the readers with glimpses of this complex scenario from different angles primarily in the context of brain and also attempts to identify the potential drug targets against neurodegenerative diseases. PMID:27114843

  14. Abnormal glutamate release in aged BTBR mouse model of autism.

    Science.gov (United States)

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality.

  15. NMR and molecular modeling: application to wine ageing

    Science.gov (United States)

    Saucier, C.; Pianet, I.; Laguerre, M.; Glories, Y.

    1998-02-01

    Red wine contains polyphenols called tannins which are very important for its taste and longevity. These polymers consist in repeating units of catechin and its epimer epicatechin. During ageing, slow condensation reactions take place which lead to new chemical structures. Among the possible reactions, we have focused our attention on acetaldehyde cross-linking. Catechin was used as a model for the production of polymers with acetaldehyde. Two reaction product fractions have been isolated by liquid chromatography. Mass measurement indicated that these fractions contain dimers. NMR (1D and 2D) and molecular modelling were then used to study the structure and conformations of these products. The first product consist in a pure dimer with the two catechin moieties connected with an ethyl bridge on the carbon 6 and 8. The second fraction was a mixture of two dimers (50/50). NMR measurements showed that it could be two symmetrical dimers involving the same carbon for each catechin moiety (6 or8). Le vin rouge contient des polyphénols appelés tanins qui sont très importants pour son goût et sa longévité. Il s'agit principalement de polymères de catéchine et d'épicatéchine. Durant le vieillissement du vin, des réactions de condensation interviennent lentement et conduisent à de nouvelles structures. Parmi les réactions possibles, nous avons plus spécialement étudié la polymérisation par pontage avec l'éthanal. La catéchine a été utilisée comme modèle de tannin et mise en présence d'éthanal en milieu acide proche du vin. Deux fractions de produits de réaction ont été isolées par chromatographie liquide. La spectrométrie de masse a révélé la présence de dimères. La RMN (1D et 2D) et la modélisation moléculaire ont ensuite été utilisées pour déterminer la structure et la conformation de ces produits. La première fraction a été identifiée comme étant un dimère de deux unités catéchines reliées par un pont éthyle par leur

  16. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

    Science.gov (United States)

    Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

    2015-06-05

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.

  17. METHODS FOR MODELING PARTICLE DEPOSITION AS A FUNCTION OF AGE. (R827352C004)

    Science.gov (United States)

    The purpose of this paper is to review the application of mathematical models of inhaled particle deposition to people of various ages. The basic considerations of aerosol physics, biological characteristics and model structure are presented along with limitations inherent in ...

  18. Age Estimates of Universe: from Globular Clusters to Cosmological Models and Probes

    CERN Document Server

    Fatima, Hira; Rahman, Syed Faisal Ur

    2016-01-01

    We performed the photometric analysis of M2 and M92 globular clusters in g and r bands of SLOAN photometric system. We transformed these g and r bands into BV bands of Johnson-Cousins photometric system and built the color magnitude diagram (CMD). We estimated the age, and metallicity of both the clusters, by fitting Padova isochrones of different age and metallicities onto the CMD. We studied Einstein and de Sitter model, bench mark model, the cosmological parameters by WMAP and Planck surveys. Finally, we compared estimated age of globular clusters to the ages from the cosmological models and cosmological parameters values of WMAP and Planck surveys.

  19. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Directory of Open Access Journals (Sweden)

    Petra Maria Hermann

    2014-12-01

    Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  20. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Science.gov (United States)

    Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

    2015-01-01

    Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular

  1. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Directory of Open Access Journals (Sweden)

    Alba Judith eMateos-Aierdi

    2015-07-01

    Full Text Available Myotonic dystrophy type I (DM1 or Steinert’s disease and type II (DM2 are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, and other clinical manifestations such as cardiomyopathy, insulin-resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc., including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTGn triplet expansion in the 3’ untranslated region of the DMPK gene, whereas (CCTGn repeats in the first intron of the CNBP/ZNF9 gene cause DM2. The expansions are transcribed into (CUGn and (CCUGn-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL, forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

  2. Constitutive modeling of the aging viscoelastic properties of portland cement paste

    Science.gov (United States)

    Grasley, Zachary C.; Lange, David A.

    2007-12-01

    Analytical approaches for modeling aging viscoelastic behavior of concrete include the time-shift approach (analogous to time-temperature superposition), the solidification theory, and the dissolution-precipitation approach. The aging viscoelastic properties of concrete are generally attributed solely to the cement paste phase since the aggregates are typically linear elastic. In this study, the aging viscoelastic behavior of four different cement pastes has been measured and modeled according to both the time-shift approach and the solidification theory. The inability of each individual model to fully characterize the aging viscoelastic response of the materials provides insight into the mechanisms for aging of the viscoelastic properties of cement paste and concrete. A model that considers aging due to solidification in combination with inherent aging of the cement paste gel (modeled using the time-shift approach) more accurately predicted the aging viscoelastic behavior of portland cement paste than either the solidification or time-shift approaches independently. The results provide evidence that solidification and other intrinsic gel aging mechanisms are concurrently active in the aging process of cementitious materials.

  3. Wettability of Sanded and Aged Fast-growing Poplar Wood Surfaces: II. Dynamic Wetting Models

    OpenAIRE

    Zhiyong Qin; Qian Zhang; Qiang Gao; Shifeng Zhang; Jianzhang Li

    2014-01-01

    The dynamic wettability of adhesive on sanded and aged wood surfaces was measured using the sessile drop method. Four different models were used to evaluate and compare the wetting process. It was shown that the wettability of freshly sanded wood and aged wood both decreased compared to the control wood. There was no evidence of change in wettability with increasing grit number. Aging reduced the wettability of the wood surface. The coefficients of determination (R2) for all four models were ...

  4. Effects of tetrahydroxystilbene - glucoside on Animal Models of Dementia or Brain Aging

    Institute of Scientific and Technical Information of China (English)

    LinLi; JinChu; LiLiu; LingZhao; LanZhang

    2004-01-01

    Aim: To investigate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) from a Chinese Medicinal Herb polygonum multiflorum on dementia or brain aging. Methods. The brain aging model of mice was developed by s. c. injection of D-galactose (50mg/kg/day) for 60 days. The Alzheimer disease (AD) model of mice

  5. Age and Creative Productivity: Nonlinear Estimation of an Information-Processing Model.

    Science.gov (United States)

    Simonton, Dean Keith

    1989-01-01

    Applied two-step cognitive model to relationship between age and creative productivity. Selected ideation and elaboration rates as information-processing parameters that define mathematical function which describes age curves and specifies their variance across disciplines. Applied non-linear estimation program to further validate model. Despite…

  6. Practical applications of age-dependent reliability models and analysis of operational data

    Energy Technology Data Exchange (ETDEWEB)

    Lannoy, A.; Nitoi, M.; Backstrom, O.; Burgazzi, L.; Couallier, V.; Nikulin, M.; Derode, A.; Rodionov, A.; Atwood, C.; Fradet, F.; Antonov, A.; Berezhnoy, A.; Choi, S.Y.; Starr, F.; Dawson, J.; Palmen, H.; Clerjaud, L

    2005-07-01

    The purpose of the workshop was to present the experience of practical application of time-dependent reliability models. The program of the workshop comprises the following sessions: -) aging management and aging PSA (Probabilistic Safety Assessment), -) modeling, -) operation experience, and -) accelerating aging tests. In order to introduce time aging effect of particular component to the PSA model, it has been proposed to use the constant unavailability values on the short period of time (one year for example) calculated on the basis of age-dependent reliability models. As for modeling, it appears that the problem of too detailed statistical models for application is the lack of data for required parameters. As for operating experience, several methods of operating experience analysis have been presented (algorithms for reliability data elaboration and statistical identification of aging trend). As for accelerated aging tests, it is demonstrated that a combination of operating experience analysis with the results of accelerated aging tests of naturally aged equipment could provide a good basis for continuous operation of instrumentation and control systems.

  7. A statistical model including age to predict passenger postures in the rear seats of automobiles.

    Science.gov (United States)

    Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

    2016-06-01

    Few statistical models of rear seat passenger posture have been published, and none has taken into account the effects of occupant age. This study developed new statistical models for predicting passenger postures in the rear seats of automobiles. Postures of 89 adults with a wide range of age and body size were measured in a laboratory mock-up in seven seat configurations. Posture-prediction models for female and male passengers were separately developed by stepwise regression using age, body dimensions, seat configurations and two-way interactions as potential predictors. Passenger posture was significantly associated with age and the effects of other two-way interaction variables depended on age. A set of posture-prediction models are presented for women and men, and the prediction results are compared with previously published models. This study is the first study of passenger posture to include a large cohort of older passengers and the first to report a significant effect of age for adults. The presented models can be used to position computational and physical human models for vehicle design and assessment. Practitioner Summary: The significant effects of age, body dimensions and seat configuration on rear seat passenger posture were identified. The models can be used to accurately position computational human models or crash test dummies for older passengers in known rear seat configurations.

  8. Optimality models in the age of experimental evolution and genomics.

    Science.gov (United States)

    Bull, J J; Wang, I-N

    2010-09-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimental context with a well-researched organism allows dissection of the evolutionary process to identify causes of model failure--whether the model is wrong about genetics or selection. Second, optimality models provide a meaningful context for the process and mechanics of evolution, and thus may be used to elicit realistic genetic bases of adaptation--an especially useful augmentation to well-researched genetic systems. A few studies of microbes have begun to pioneer this new direction. Incompatibility between the assumed and actual genetics has been demonstrated to be the cause of model failure in some cases. More interestingly, evolution at the phenotypic level has sometimes matched prediction even though the adaptive mutations defy mechanisms established by decades of classic genetic studies. Integration of experimental evolutionary tests with genetics heralds a new wave for optimality models and their extensions that does not merely emphasize the forces driving evolution.

  9. Complex Behavior in a Selective Aging Neuron Model Based on Small World Networks

    Institute of Scientific and Technical Information of China (English)

    LUO Min-Jie; ZHANG Gui-Qing; LIU Qiu-Yu; CHEN Tian-Lun

    2008-01-01

    Complex behavior in a selective aging simple neuron model based on small world networks is investigated. The basic elements of the model are endowed with the main features of a neuron function. The structure of the selective aging neuron model is discussed. We also give some properties of the new network and find that the neuron model displays a power-law behavior. If the brain network is small world-like network, the mean avalanche size is almost the same unless the aging parameter is big enough.

  10. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    Science.gov (United States)

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  11. Age-related changes in predictive capacity versus internal model adaptability: electrophysiological evidence that individual differences outweigh effects of age

    Directory of Open Access Journals (Sweden)

    Ina eBornkessel-Schlesewsky

    2015-11-01

    Full Text Available Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs were measured in a group of older adults (60–81 years; n=40 as they read sentences of the form The opposite of black is white/yellow/nice. Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (white; an effect assumed to reflect a prediction match, and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, nice, versus the incongruous associated condition, yellow. These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to cognitive

  12. Maturity Models in the Age of Digital Diversity

    DEFF Research Database (Denmark)

    Andersen, Kim Normann; Henriksen, Helle Zinner; Medaglia, Rony

    2012-01-01

    the view that e-government is focused in a formal organizational span of control. We propose a refined operationalization of the PPR maturity model, arguing that the activities and individual workers within the public sector and the citizens using and co-producing the public services will be the vehicle......This chapter proposes a reorientation of the e-government maturity models by focusing on the activities rather than on the formal organizational structures and have the citizens as the key stakeholder for future e-government investments. We draw upon a discussion on the limitations of the popular e......-government maturity model by Layne and Lee [1] included in the proposal of the Public Sector Process Rebuilding (PPR) model [2, 3]. The adoption and adaptation of Web 2.0 platforms and location-based services, and the parallel extension of conventional technologies as SMS and web-based self-services, challenge...

  13. The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice

    Directory of Open Access Journals (Sweden)

    David Harrison

    2011-06-01

    Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

  14. In vitro 3-D model based on extending time of culture for studying chronological epidermis aging.

    Science.gov (United States)

    Dos Santos, Morgan; Metral, Elodie; Boher, Aurélie; Rousselle, Patricia; Thepot, Amélie; Damour, Odile

    2015-09-01

    Skin aging is a complex phenomenon in which several mechanisms operate simultaneously. Among them, intrinsic aging is a time-dependent process, which leads to gradual skin changes affecting its structure and function such as thinning down of both epidermal and dermal compartments and a flattening and fragility of the dermo-epidermal junction. Today, several approaches have been proposed for the generation of aged skin in vitro, including skin explants from aged donors and three-dimensional skin equivalent treated by aging-inducing chemical compounds or engineered with human cells isolated from aged donors. The aim of this study was to develop and validate a new in vitro model of aging based on skin equivalent demonstrating the same phenotypic changes that were observed in chronological aging. By using prolonged culture as a proxy for cellular aging, we extended to 120 days the culture time of a skin equivalent model based on collagen-glycosaminoglycan-chitosan porous polymer and engineered with human skin cells from photo-protected sites of young donors. Morphological, immunohistological and ultrastructural analysis at different time points of the culture allowed characterizing the phenotypic changes observed in our model in comparison to samples of non photo-exposed normal human skin from different ages. We firstly confirmed that long-term cultured skin equivalents are still morphologically consistent and functionally active even after 120 days of culture. However, similar to in vivo chronological skin aging a significant decrease of the epidermis thickness as well as the number of keratinocyte expressing proliferation marker Ki67 are observed in extended culture time skin equivalent. Epidermal differentiation markers loricrin, filaggrin, involucrin and transglutaminase, also strongly decreased. Ultrastructural analysis of basement membrane showed typical features of aged skin such as duplication of lamina densa and alterations of hemidesmosomes. Moreover, the

  15. Aging-like skin changes induced by ultraviolet irradiation in an animal model of metabolic syndrome.

    Science.gov (United States)

    Akase, Tomoko; Nagase, Takashi; Huang, Lijuan; Ibuki, Ai; Minematsu, Takeo; Nakagami, Gojiro; Ohta, Yasunori; Shimada, Tsutomu; Aburada, Masaki; Sugama, Junko; Sanada, Hiromi

    2012-04-01

    Both physiological skin aging and pathologic photo-aging caused by ultraviolet (UV) irradiation are mediated by latent inflammation and oxidative stress. Although numerous animal skin-aging models have used UV irradiation, most require massive doses or long-term irradiation. To establish a more refined skin-aging model, we focused on an animal model of metabolic syndrome (MS) because MS involves damage to various organs via oxidative stress or inflammation, similar to the changes associated with aging. We hypothesized that MS skin might exhibit more aging-like changes after milder, shorter-term UV irradiation than would normal animal skin under similar conditions, thus providing a useful model for skin aging. The authors therefore examined the skin from Tsumura Suzuki obese diabetic (TSOD) mice (MS model) and control Tsumura Suzuki non-obese (TSNO) mice before and after UV irradiation. Skin from TSOD mice had a thinner epidermis and dermis, a thicker fatty layer, reduced density and convolution of the fragmented collagen fibers, and upregulated expression of tumor necrosis factor (TNF)-α, a dual marker for inflammation and aging, compared to the skin from TSNO mice. UV irradiation affected TSOD skin more severely than TSNO skin, resulting in various changes resembling those in aged human skin, including damage to the dermis and subcutaneous fatty tissue, infiltration of inflammatory cells, and further upregulation of TNF-α expression. These results suggest that UV-irradiated TSOD mice may provide a new model of skin aging and imply that skin from humans with MS is more susceptible to UV- or aging-related damage than normal human skin.

  16. Mesoscopic model of temporal and spatial heterogeneity in aging colloids

    DEFF Research Database (Denmark)

    Becker, Nikolaj; Sibani, Paolo; Boettcher, Stefan;

    2014-01-01

    on a small set of principles, our model provides emergent dynamic heterogeneity, reproduces the known results for dense hard sphere colloids and makes detailed, experimentally-testable predictions for canonical observables in glassy dynamics. In particular, we reproduce the shape of the intermediate...

  17. A Model to Determine the Likely Age of an Adolescent’s First Drink of Alcohol

    Science.gov (United States)

    Chan, Grace; Kramer, John R.; Wetherill, Leah; Bucholz, Kathleen K.; Dick, Danielle; Hesselbrock, Victor; Porjesz, Bernice; Rangaswamy, Madhavi; Schuckit, Marc

    2013-01-01

    OBJECTIVE: With the use of a new cohort of adolescent subjects, predictors from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview and the Achenbach Youth Self Report (YSR) were combined to model age of first drink (AFD). METHODS: Subjects consisted of 820 adolescents (ages 14–17) drawn from the current phase of the Collaborative Study on the Genetics of Alcoholism. Three Cox proportional hazards models were considered. Model 1 contained SSAGA variables equivalent to AFD predictors from our previous study: interview age, family history of alcohol dependence, and number of conduct disorder symptoms. Model 2 incorporated 2 additional SSAGA questions (best friends drink and smoked a cigarette before a reported AFD) plus 8 YSR-derived scale scores. Model 3 was a reduced version of model 2, retaining only significant predictors. RESULTS: Model 2 was a significant improvement over model 1. Model 3 was the best and the most parsimonious of the 3 with respect to likelihood ratio and Wald χ2 tests and retained only 5 variables from model 2. Included variables were the following: (1) best friends drink, (2) membership in a high-risk alcohol dependence family, (3) number of conduct disorder symptoms, (4) YSR externalizing score, and (5) YSR social problems score. CONCLUSIONS: Adding variables to those from our original study improved our ability to model the likely age of alcohol initiation. In addition to the SSAGA, the YSR appears to have utility as a research tool to predict the age of alcohol initiation. PMID:23296431

  18. Simulations of a mortality plateau in the sexual Penna model for biological aging

    Science.gov (United States)

    Schwämmle, V.; de Oliveira, S. Moss

    2005-09-01

    The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individual genomes are represented by bit strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n , reaches a threshold value T . Since the mean number of diseases increases with age, the probability to die is zero for very young ages (ngenetic death age, we test several other functions that may or may not slightly increase the death probability at young ages (nages. By imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age structure of the population, and the death probability.

  19. Dynamic analysis of a hepatitis B model with three-age-classes

    Science.gov (United States)

    Zhang, Suxia; Zhou, Yicang

    2014-07-01

    Based on the fact that the likelihood of becoming chronically infected is dependent on age at primary infection Kane (1995) [2], Edmunds et al. (1993) [3], Medley et al. (2001) [4], and Ganem and Prince (2004) [6], we formulate a hepatitis B transmission model with three age classes. The reproduction number, R0 is defined and the dynamical behavior of the model is analyzed. It is proved that the disease-free equilibrium is globally stable if R01. The unique endemic equilibrium and its global stability is obtained in a special case. Simulations are also conducted to compare the dynamical behavior of the model with and without age classes.

  20. Adaptation to stroke using a model of successful aging.

    Science.gov (United States)

    Donnellan, C; Hevey, D; Hickey, A; O'Neill, D

    2012-01-01

    The process of adaptation to the physical and psychosocial consequences after stroke is a major challenge for many individuals affected. The aim of this study was to examine if stroke patients within 1 month of admission (n = 153) and followed up at 1 year (n = 107) engage in selection, optimization, and compensation (SOC) adaptive strategies and the relationship of these strategies with functional ability, health-related quality of life (HRQOL) and depression 1 year later. Adaptive strategies were measured using a 15-item SOC questionnaire. Internal and external resources were assessed including recovery locus of control, stroke severity, and socio-demographics. Outcome measures were the Stroke Specific Quality of Life Questionnaire (SS-QoL), the Nottingham Extended Activities of Daily Living Scale and the Depression Subscale of the Hospital Anxiety and Depression Scale. Findings indicated that stroke patients engaged in the use of SOC strategies but the use of these strategies were not predictive of HRQOL, functional ability or depression 1 year after stroke. The use of SOC strategies were not age specific and were consistent over time, with the exception of the compensation subscale. Results indicate that SOC strategies may potentially be used in response to loss regulation after stroke and that an individual's initial HRQOL functional ability, levels of depression and socio-economic status that are important factors in determining outcome 1 year after stroke. A stroke-specific measure of SOC may be warranted in order to detect significant differences in determining outcomes for a stroke population.

  1. The crucial role of the Pls1 tetraspanin during ascospore germination in Podospora anserina provides an example of the convergent evolution of morphogenetic processes in fungal plant pathogens and saprobes.

    Science.gov (United States)

    Lambou, Karine; Malagnac, Fabienne; Barbisan, Crystel; Tharreau, Didier; Lebrun, Marc-Henri; Silar, Philippe

    2008-10-01

    Pls1 tetraspanins were shown for some pathogenic fungi to be essential for appressorium-mediated penetration into their host plants. We show here that Podospora anserina, a saprobic fungus lacking appressorium, contains PaPls1, a gene orthologous to known PLS1 genes. Inactivation of PaPls1 demonstrates that this gene is specifically required for the germination of ascospores in P. anserina. These ascospores are heavily melanized cells that germinate under inducing conditions through a specific pore. On the contrary, MgPLS1, which fully complements a DeltaPaPls1 ascospore germination defect, has no role in the germination of Magnaporthe grisea nonmelanized ascospores but is required for the formation of the penetration peg at the pore of its melanized appressorium. P. anserina mutants with mutation of PaNox2, which encodes the NADPH oxidase of the NOX2 family, display the same ascospore-specific germination defect as the DeltaPaPls1 mutant. Both mutant phenotypes are suppressed by the inhibition of melanin biosynthesis, suggesting that they are involved in the same cellular process required for the germination of P. anserina melanized ascospores. The analysis of the distribution of PLS1 and NOX2 genes in fungal genomes shows that they are either both present or both absent. These results indicate that the germination of P. anserina ascospores and the formation of the M. grisea appressorium penetration peg use the same molecular machinery that includes Pls1 and Nox2. This machinery is specifically required for the emergence of polarized hyphae from reinforced structures such as appressoria and ascospores. Its recurrent recruitment during fungal evolution may account for some of the morphogenetic convergence observed in fungi.

  2. Dynamical network model for age-related health deficits and mortality

    Science.gov (United States)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  3. Exploring Demographic Shifts: Aging and Migration Exploratory Group Model Specification & Simulation

    NARCIS (Netherlands)

    Pruyt, E.; Logtens, T.; Gijsbers, G.

    2011-01-01

    Plausible dynamics of a major demographic shift –(societal) aging– is studied in this paper, both from a global perspective and from a national perspective. Several economic, political and social implications of aging and aging-related demographic shifts are explored using System Dynamics models as

  4. Aging Well and the Environment: Toward an Integrative Model and Research Agenda for the Future

    Science.gov (United States)

    Wahl, Hans-Werner; Iwarsson, Susanne; Oswald, Frank

    2012-01-01

    Purpose of the Study: The effects of the physical-spatial-technical environment on aging well have been overlooked both conceptually and empirically. In the spirit of M. Powell Lawton's seminal work on aging and environment, this article attempts to rectify this situation by suggesting a new model of how older people interact with their…

  5. Lyapunov functions and global stability for SIR and SEIR models with age-dependent susceptibility

    KAUST Repository

    Korobeinikov, Andrei

    2013-01-01

    We consider global asymptotic properties for the SIR and SEIR age structured models for infectious diseases where the susceptibility depends on the age. Using the direct Lyapunov method with Volterra type Lyapunov functions, we establish conditions for the global stability of a unique endemic steady state and the infection-free steady state.

  6. Existence and Uniqueness of Endemic States for the Age-structured MSEIR Epidemic Model

    Institute of Scientific and Technical Information of China (English)

    Xue-zhi Li; Geni Gupur; Guang-tian Zhu

    2002-01-01

    The existence and uniqueness of positive steady states for the age-structured MSEIR epidemic model with age-dependent transmission coefficient is considered. Threshold results for the existence of endemic states are established; under certain conditions, uniqueness is also shown.

  7. Combined age and segregated kinetic model for industrial-scale penicillin fed-batch cultivation

    NARCIS (Netherlands)

    Wang, Z.F.; Lauwerijssen, M.J.C.; Yuan, J.Q.

    2005-01-01

    This paper proposes a cell age model forPenicillium chrysogenum fed-batch cultivation to supply a qualitative insight into morphology-associated dynamics. The average ages of the segregated cell populations, such as growing cells, non-growing cells and intact productive cells, were estimated by this

  8. Lyapunov functions and global stability for SIR and SEIR models with age-dependent susceptibility.

    Science.gov (United States)

    Melnik, Andrey V; Korobeinikov, Andrei

    2013-04-01

    We consider global asymptotic properties for the SIR and SEIR age structured models for infectious diseases where the susceptibility depends on the age. Using the direct Lyapunov method with Volterra type Lyapunov functions, we establish conditions for the global stability of a unique endemic steady state and the infection-free steady state.

  9. Model of human aging: Recent findings on Werner’s and Hutchinson-Gilford progeria syndromes

    Directory of Open Access Journals (Sweden)

    Shian-ling Ding

    2008-09-01

    Full Text Available Shian-ling Ding1, Chen-Yang Shen2,3,41Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan; 2Institute of Biomedical Sciences, and 3Life Science Library, Academia Sinica, Taipei, Taiwan; 4Graduate Institute of Environmental Science, China Medical University, Taichong, TaiwanAbstract: The molecular mechanisms involved in human aging are complicated. Two progeria syndromes, Werner’s syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, characterized by clinical features mimicking physiological aging at an early age, provide insights into the mechanisms of natural aging. Based on recent findings on WS and HGPS, we suggest a model of human aging. Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage. In telomere-dependent aging, telomere shortening and dysfunction may lead to DNA damage responses which induce cellular senescence. In DNA damage-initiated aging, DNA damage accumulates, along with DNA repair deficiencies, resulting in genomic instability and accelerated cellular senescence. In addition, aging due to both mechanisms (DNA damage and telomere shortening is strongly dependent on p53 status. These two mechanisms can also act cooperatively to increase the overall level of genomic instability, triggering the onset of human aging phenotypes.Keywords: human aging, Hutchinson-Gilford Progeria syndrome, Werner syndrome

  10. Mathematical modeling of left ventricular dimensional changes in mice during aging

    Directory of Open Access Journals (Sweden)

    Yang Tianyi

    2012-12-01

    Full Text Available Abstract Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV, which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age.

  11. Characterization of plasma thiol redox potential in a common marmoset model of aging

    Directory of Open Access Journals (Sweden)

    James R. Roede

    2013-01-01

    Full Text Available Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys, cystine (CySS, glutathione (GSH and glutathione disulfide (GSSG. Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (EhCySS is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (Eh to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging.

  12. Material modelling for creep-age forming of aluminium alloy 7B04

    Directory of Open Access Journals (Sweden)

    Lam Aaron C.L.

    2015-01-01

    Full Text Available This paper presents a study on the creep-ageing behaviour of a peak-aged aluminium alloy 7B04 under different tensile loads at 115oC and subsequently modelling it for creep-age forming (CAF applications. Mechanical properties and microstructural evolutions of creep-aged specimens were investigated. The material was modelled using a set of unified constitutive equations, which not only captures the material's creep deformation but also takes into account yield strength contributions from solid solution hardening, age hardening and dislocation hardening during creep-ageing. A possible application of the present work is demonstrated by implementing the determined material model into a commercial finite element analysis solver via a user-defined subroutine for springback prediction of creep-age formed plates. A good agreement is observed between the simulated springback values and experimental results. This material model now enables further investigations of 7B04 under various CAF scenarios to be conducted inexpensively via computational modelling.

  13. A genetic program theory of aging using an RNA population model.

    Science.gov (United States)

    Wang, Xiufang; Ma, Zhihong; Cheng, Jianjun; Lv, Zhanjun

    2014-01-01

    Aging is a common characteristic of multicellular eukaryotes. Copious hypotheses have been proposed to explain the mechanisms of aging, but no single theory is generally acceptable. In this article, we refine the RNA population gene activating model (Lv et al., 2003) based on existing reports as well as on our own latest findings. We propose the RNA population model as a genetic theory of aging. The new model can also be applied to differentiation and tumorigenesis and could explain the biological significance of non-coding DNA, RNA, and repetitive sequence DNA. We provide evidence from the literature as well as from our own findings for the roles of repetitive sequences in gene activation. In addition, we predict several phenomena related to aging and differentiation based on this model.

  14. Aging and Immortality in a Cell Proliferation Model

    CERN Document Server

    Antal, T; Trugman, S A; Redner, S

    2007-01-01

    We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.

  15. Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.

    Science.gov (United States)

    Jafari, Mahtab

    2010-01-01

    Understanding the causes of aging is a complex problem due to the multiple factors that influence aging, which include genetics, environment, metabolism and reproduction, among others. These multiple factors create logistical difficulties in the evaluation of anti-aging agents. There is a need for good model systems to evaluate potential anti-aging compounds. The model systems used should represent the complexities of aging in humans, so that the findings may be extrapolated to human studies, but they should also present an opportunity to minimize the variables so that the experimental results can be accurately interpreted. In addition to positively affecting lifespan, the impact of the compound on the physiologic confounders of aging, including fecundity and the health span--the period of life where an organism is generally healthy and free from serious or chronic illness--of the model organism needs to be evaluated. Fecundity is considered a major confounder of aging in fruit flies. It is well established that female flies that are exposed to toxic substances typically reduce their dietary intake and their reproductive output and display an artifactual lifespan extension. As a result, drugs that achieve longevity benefits by reducing fecundity as a result of diminished food intake are probably not useful candidates for eventual treatment of aging in humans and should be eliminated during the screening process. Drosophila melanogaster provides a suitable model system for the screening of anti-aging compounds as D. melanogaster and humans have many conserved physiological and biological pathways. In this paper, I propose an algorithm to screen anti-aging compounds using Drosophila melanogaster as a model system.

  16. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    Science.gov (United States)

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan; Shirzad, Hedayatolah

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.

  17. Compact attractors for time-periodic age-structured population models

    Directory of Open Access Journals (Sweden)

    Pierre Magal

    2001-10-01

    Full Text Available In this paper we investigate the existence of compact attractors for time-periodic age-structured models. So doing we investigate the eventual compactness of a class of abstract non-autonomous semiflow (non necessarily periodic. We apply this result to non-autonomous age-structured models. In the time periodic case, we obtain the existence of a periodic family of compact subsets that is invariant by the semiflow, and attract the solutions of the system.

  18. Model calculations of the age of firn air across the Antarctic continent

    OpenAIRE

    2004-01-01

    The age of firn air in Antarctica at pore close-off depth is only known for a few specific sites where firn air has been sampled for analyses. We present a model that calculates the age of firn air at pore close-off depth for the entire Antarctic continent. The model basically uses four meteorological parameters as input (surface temperature, pressure, accumulation rate and wind speed). Using parameterisations for surface snow density, pore close-off density and tortuosity, ...

  19. Modeling the multiday evolution and aging of secondary organic aerosol during MILAGRO 2006.

    Science.gov (United States)

    Dzepina, Katja; Cappa, Christopher D; Volkamer, Rainer M; Madronich, Sasha; Decarlo, Peter F; Zaveri, Rahul A; Jimenez, Jose L

    2011-04-15

    In this study, we apply several recently proposed models to the evolution of secondary organic aerosols (SOA) and organic gases advected from downtown Mexico City at an altitude of ∼3.5 km during three days of aging, in a way that is directly comparable to simulations in regional and global models. We constrain the model with and compare its results to available observations. The model SOA formed from oxidation of volatile organic compounds (V-SOA) when using a non-aging SOA parameterization cannot explain the observed SOA concentrations in aged pollution, despite the increasing importance of the low-NO(x) channel. However, when using an aging SOA parameterization, V-SOA alone is similar to the regional aircraft observations, highlighting the wide diversity in current V-SOA formulations. When the SOA formed from oxidation of semivolatile and intermediate volatility organic vapors (SI-SOA) is computed following Robinson et al. (2007) the model matches the observed SOA mass, but its O/C is ∼2× too low. With the parameterization of Grieshop et al. (2009), the total SOA mass is ∼2× too high, but O/C and volatility are closer to the observations. Heating or dilution cause the evaporation of a substantial fraction of the model SOA; this fraction is reduced by aging although differently for heating vs dilution. Lifting of the airmass to the free-troposphere during dry convection substantially increases SOA by condensation of semivolatile vapors; this effect is reduced by aging.

  20. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    Science.gov (United States)

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age.

  1. Construction of Spectral Discoloration Model for Red Lead Pigment by Aging Test and Simulating Degradation Experiment

    Directory of Open Access Journals (Sweden)

    Jinxing Liang

    2016-01-01

    Full Text Available The construction of spectral discoloration model, based on aging test and simulating degradation experiment, was proposed to detect the aging degree of red lead pigment in ancient murals and to reproduce the spectral data supporting digital restoration of the ancient murals. The degradation process of red lead pigment under the aging test conditions was revealed by X-ray diffraction, scanning electron microscopy, and spectrophotometer. The simulating degradation experiment was carried out by proportionally mixing red lead and lead dioxide with referring to the results of aging test. The experimental result indicated that the pure red lead was gradually turned into black lead dioxide, and the amount of tiny particles of the aging sample increased faced with aging process. Both the chroma and lightness of red lead pigment decreased with discoloration, and its hue essentially remains unchanged. In addition, the spectral reflectance curves of the aging samples almost started rising at about 550 nm with the inflection moving slightly from about 570 nm to 550 nm. The spectral reflectance of samples in long- and in short-wavelength regions was fitted well with the logarithmic and linear function. The spectral discoloration model was established, and the real aging red lead pigment in Dunhuang murals was measured and verified the effectiveness of the model.

  2. Rheological model for sol-gel phase transition of thermo-aged heavy oil fractions

    Directory of Open Access Journals (Sweden)

    Xiomara Andrea Vargas Arenas

    2010-05-01

    Full Text Available A power-law rheological model is proposed in this paper: G’’ (ω ∼ ωn and G’ (ω ~ ωn. It represents the increased connectivity between thermo-aged asphalt molecules in a rheo-reactor as one of the applications of systematic rheology. The results confirmed a sol-gel phase transition tendency for aged asphalt in the experimental frequency window at temperatures below 40°C. Such pattern could have been related to the structuring effect arising from the thermo-oxidative asphalt aging process during continuous agitation which has been suitably described by the micellar model of asphalt.

  3. Atomistic Model of Physical Ageing in Se-rich As-Se Glasses

    Energy Technology Data Exchange (ETDEWEB)

    Golovchak,R.; Shpotyuk, O.; Kozdras, A.; Bureau, B.; Vlcek, M.; Ganjoo, A.; Jain, H.

    2007-01-01

    Thermal, optical, X-ray excited and magnetic methods were used to develop a microstructural model of physical ageing in Se-rich glasses. The glass composition As10Se90, possessing a typical cross-linked chain structure, was chosen as a model object for the investigations. The effect of physical ageing in this glass was revealed by differential scanning calorimetry, whereas the corresponding changes in its atomic arrangement were studied by extended X-ray absorption fine structure, Raman and solid-state 77Se nuclear magnetic resonance spectroscopy. Straightening-shrinkage processes are shown to be responsible for the physical ageing in this Se-rich As-Se glass.

  4. Dynamical Masses of Young Stars I: Discordant Model Ages of Upper Scorpius

    CERN Document Server

    Rizzuto, Aaron C; Dupuy, Trent J; Kraus, Adam L

    2015-01-01

    We present the results of a long term orbit monitoring program, using sparse aperture masking observations taken with NIRC2 on the Keck-II telescope, of seven G to M-type members of the Upper Scorpius subgroup of the Sco-Cen OB association. We present astrometry and derived orbital elements of the binary systems we have monitored, and also determine the age, component masses, distance and reddening for each system using the orbital solutions and multi-band photometry, including Hubble Space Telescope photometry, and a Bayesian fitting procedure. We find that the models can be forced into agreement with any individual system by assuming an age, but that age is not consistent across the mass range of our sample. The G-type binary systems in our sample have model ages of ~11.5 Myr, which is consistent with the latest age estimates for Upper Scorpius, while the M-type binary systems have significantly younger model ages of ~7 Myr. Based on our fits, this age discrepancy in the models corresponds to a luminosity u...

  5. Toward Reducing Ageism: PEACE (Positive Education about Aging and Contact Experiences) Model.

    Science.gov (United States)

    Levy, Sheri R

    2016-08-10

    The population of older adults is growing worldwide. Negative ageism (negative attitudes and behavior toward older adults) is a serious international concern that negatively influences not only older adults but also individuals across the age continuum. This article proposes and examines the application of an integrative theoretical model across empirical evidence in the literature on ageism in psychology, medicine, social work, and sociology. The proposed Positive Education about Aging and Contact Experiences (PEACE) model focuses on 2 key contributing factors expected to reduce negative ageism: (a) education about aging including facts on aging along with positive older role models that dispel negative and inaccurate images of older adulthood; and (b) positive contact experiences with older adults that are individualized, provide or promote equal status, are cooperative, involve sharing of personal information, and are sanctioned within the setting. These 2 key contributing factors have the potential to be interconnected and work together to reduce negative stereotypes, aging anxiety, prejudice, and discrimination associated with older adults and aging. This model has implications for policies and programs that can improve the health and well-being of individuals, as well as expand the residential, educational, and career options of individuals across the age continuum.

  6. Parameterization of European perch Perca fluviatilis length-at-age data using stochastic Gompertz growth models.

    Science.gov (United States)

    Troynikov, V S; Gorfine, H K; Ložys, L; Pūtys, Z; Jakubavičiūtė, E; Day, R W

    2011-12-01

    Three stochastic versions of the Gompertz growth model were used to parameterize total length (L(T) )-at-age data for perch Perca fluviatilis, an important target species for commercial and recreational fishers and a food species for predatory fishes and aquatic birds. Each model addresses growth heterogeneity by incorporating random parameters from a specific positive distribution: Weibull, gamma or log-normal. The modelling outputs for each version of the model provide L(T) distributions for selected ages and percentiles of L(T) at age for both males and females. The results highlight the importance of using a stochastic approach and the logistic-like growth pattern for analysing growth data for P. fluviatilis in Curonian Lagoon (Lithuania). Outputs from this modelling can be extended to a stochastic analysis of fish cohort dynamics, incorporating all length-based biological relationships, and the selectivity-related interactions between fish cohorts and fishing gear.

  7. Modeling the Ages and Metallicities of Early-Type Galaxies in Fundamental Plane Space

    CERN Document Server

    Porter, L A; Primack, J R; Croton, D J; Covington, M D; Graves, G J; Faber, S M

    2014-01-01

    Recent observations have probed the formation histories of nearby elliptical galaxies by tracking correlations between the stellar population parameters, age and metallicity, and the structural parameters that enter the Fundamental Plane, radius and velocity dispersion sigma. These studies have found intriguing correlations between these four parameters. In this work, we make use of a semi-analytic model, based on halo merger trees extracted from the Bolshoi cosmological simulation, that predicts the structural properties of spheroid-dominated galaxies based on an analytic model that has been tested and calibrated against an extensive suite of hydrodynamic+N-body binary merger simulations. We predict the radius, sigma, luminosity, age, and metallicity of spheroid-dominated galaxies, enabling us to compare directly to observations. Our model predicts a strong correlation between age and sigma for early-type galaxies, and no significant correlation between age and radius, in agreement with observations. In addi...

  8. Numerical simulations of the phase separation properties for the thermal aged CDSS with Phase Field Model

    Energy Technology Data Exchange (ETDEWEB)

    Xue Fei [Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China); Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); Wang Zhaoxi, E-mail: wangzx03@mails.tsinghua.edu.cn [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); Applied Mechanics Laboratory, Tsinghua University, Beijing 100084 (China); Zhang Guodong [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); School of Mechanical and Power Engineering, Nanjing University of Technology, Nanjing 210009 (China); Qu Baoping; Shi Huiji [Applied Mechanics Laboratory, Tsinghua University, Beijing 100084 (China); Shu Guogang [Suzhou Nuclear Power Research Institute, Suzhou 215004 (China); Liu Wei [Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2011-07-15

    Highlights: > Thermal aging causes the Cr-rich phase precipitate and form clusters. > Phase field dynamic model is used for simulating the phase separation coarsening. > Damage initiated more easily in the ferrite matrix for the Cr clusters. - Abstract: Experiments and numerical simulations with Phase Field Model and Finite Element Analysis were carried out to investigate the phase separation dynamic properties and the corresponding thermal aging degradation mechanism. Experimental results from transmission electron microscopy and atomic force microscopy show that thermal aging causes the Cr-rich phase precipitate and form clusters. A phase field dynamic model was developed with constitutive relations and empirical potential functions to investigate the phase separation dynamics in the ferrite phase. Numerical results integrated with cell dynamical system method show clearly the micro structure morphology and the phase separation coarsening with aging time. The evolution process of the phase separation was quantitatively illustrated and reproduced macroscopically. The scattering pattern becomes clearer and the corresponding radius becomes smaller along with the increasing aging time. The average characteristic length increases firstly then decreases and enters a more stable stage. With the increment of the local Cr concentration, the evolution of the phase morphology was quite different. Finite Element Analysis simulation results with the Gurson-Tvergaard-Needleman void model show that the damage initiated more easily in the ferrite matrix for the Cr atoms forming clusters with increasing aging time. The phenomenological simulations with Phase Field Model and Finite Element Analysis were in remarkably good agreement with experimental results and analytical considerations.

  9. Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution

    Directory of Open Access Journals (Sweden)

    Ivan B. Djordjevic

    2015-08-01

    Full Text Available Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i Markovian classical model, (ii Markovian-like quantum model, and (iii hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage Markov chain-like models of aging, which

  10. Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution.

    Science.gov (United States)

    Djordjevic, Ivan B

    2015-08-24

    Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum model, and (iii) hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage) Markov chain-like models of aging, which are mutually

  11. Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging.

    Science.gov (United States)

    Patterson, David; Cabelof, Diane C

    2012-04-01

    Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate metabolism and oxidative stress in the dysregulation of BER in Down syndrome. Further, we suggest these pathways are involved in the leukemogenesis of Down syndrome. We have reviewed the role of BER in the processing of oxidative stress, and the impact of folate depletion on BER capacity. Further, we have reviewed the role that loss of BER, specifically DNA polymerase beta, plays in accelerating the rate of aging. Like that seen in the DNA polymerase beta heterozygous mouse, the aging phenotype of Down syndrome is subtle, unlike the aging phenotypes seen in the classical progeroid syndromes and mouse models of aging. As such, Down syndrome may provide a model for elucidating some of the basic mechanisms of aging.

  12. Hutchinson-Gilford progeria syndrome as a model for vascular aging.

    Science.gov (United States)

    Brassard, Jonathan A; Fekete, Natalie; Garnier, Alain; Hoesli, Corinne A

    2016-02-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease.

  13. Accelerated Aging of Intervertebral Discs in a Mouse Model of Progeria

    Science.gov (United States)

    Vo, Nam; Seo, Hyoung-Yeon; Robinson, Andria; Sowa, Gwendolyn; Bentley, Douglas; Taylor, Lauren; Studer, Rebecca; Usas, Arvydas; Huard, Johnny; Alber, Sean; Watkins, Simon C.; Lee, Joon; Coehlo, Paulo; Wang, Dong; Loppini, Mattia; Robbins, Paul D.; Niedernhofer, Laura J.; Kang, James

    2012-01-01

    Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1−/Δ mice). The ERCC1-deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild-type littermates, Ercc1−/Δ mice also exhibit other age-related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age-associated disc pathologies was further accelerated in Ercc1−/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1−/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis. PMID:20973062

  14. Aging influence on grey matter structural associations within the default mode network utilizing Bayesian network modeling

    Directory of Open Access Journals (Sweden)

    Yan eWang

    2014-05-01

    Full Text Available Recent neuroimaging studies have revealed normal aging-related alterations in functional and structural brain networks such as the default mode network (DMN. However, less is understood about specific brain structural dependencies or interactions between brain regions within the DMN in the normal aging process. In this study, using Bayesian network (BN modeling, we analyzed grey matter volume data from 109 young and 82 old subjects to characterize the influence of aging on associations between core brain regions within the DMN. Furthermore, we investigated the discriminability of the aging-associated BN models for the young and old groups. Compared to their young counterparts, the old subjects showed significant reductions in connections from right inferior temporal cortex (ITC to medial prefrontal cortex (mPFC, right hippocampus (HP to right ITC, and mPFC to posterior cingulate cortex (PCC and increases in connections from left HP to mPFC and right inferior parietal cortex (IPC to right ITC. Moreover, the classification results showed that the aging-related BN models could predict group membership with 88.48% accuracy, 88.07% sensitivity and 89.02% specificity. Our findings suggest that structural associations within the DMN may be affected by normal aging and provide crucial information about aging effects on brain structural networks.

  15. Aging Influence on Gray Matter Structural Associations within the Default Mode Network Utilizing Bayesian Network Modeling.

    Science.gov (United States)

    Wang, Yan; Chen, Kewei; Zhang, Jiacai; Yao, Li; Li, Ke; Jin, Zhen; Ye, Qing; Guo, Xiaojuan

    2014-01-01

    Recent neuroimaging studies have revealed normal aging-related alterations in functional and structural brain networks such as the default mode network (DMN). However, less is understood about specific brain structural dependencies or interactions between brain regions within the DMN in the normal aging process. In this study, using Bayesian network (BN) modeling, we analyzed gray matter volume data from 109 young and 82 old subjects to characterize the influence of aging on associations between core brain regions within the DMN. Furthermore, we investigated the discriminability of the aging-associated BN models for the young and old groups. Compared to their young counterparts, the old subjects showed significant reductions in connections from right inferior temporal cortex (ITC) to medial prefrontal cortex (mPFC), right hippocampus (HP) to right ITC, and mPFC to posterior cingulate cortex and increases in connections from left HP to mPFC and right inferior parietal cortex to right ITC. Moreover, the classification results showed that the aging-related BN models could predict group membership with 88.48% accuracy, 88.07% sensitivity, and 89.02% specificity. Our findings suggest that structural associations within the DMN may be affected by normal aging and provide crucial information about aging effects on brain structural networks.

  16. Mathematical Modeling of Age and of Income Distribution Associated with Female Marriage Migration in Rajshahi, Bangladesh

    Directory of Open Access Journals (Sweden)

    Rafiqul Islam

    2012-08-01

    Full Text Available An effort has been made, in this study, to fit mathematical models to age and income distribution associated with female marriage migration in Rajshahi district, Bangladesh. For this, the data is taken under the project entitled “Strengthening the Department of Population Science and Human Resource Development” in collaboration with UNFPA, Bangladesh. It is found that marriage migration associated with age follows polynomial model and income distribution associated with female marriage migration follows two parameters positive exponential model. To verify the adequacy and steadiness situation of the model, Cross Validity Prediction Power (CVPP and F-test are employed to these models. The contribution of this paper to knowledge is the fitted cubic polynomial model and positive exponential model to the migration data aggregate.

  17. EXISTENCE AND UNIQUENESS OF ENDEMIC STATES FOR THE AGE-STRUCTURED SEIR EPIDEMIC MODEL

    Institute of Scientific and Technical Information of China (English)

    Xuezhi LI; Jing CHEN

    2006-01-01

    An age-structured SEIR epidemic model of a vertically as well as horizontally transmitted disease is investigated. Threshold results for the existence of endemic states are established for most cases. Under certain conditions, uniqueness is also shown. Threshold used are explicitly computable in term of demographic and epidemiological parameters of the model.

  18. Accounting for correlated observations in an age-based state-space stock assessment model

    DEFF Research Database (Denmark)

    Berg, Casper Willestofte; Nielsen, Anders

    2016-01-01

    Fish stock assessment models often relyon size- or age-specific observations that are assumed to be statistically independent of each other. In reality, these observations are not raw observations, but rather they are estimates from a catch-standardization model or similar summary statistics based...

  19. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    Science.gov (United States)

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P treatment prevented age-induced anxiety-like behavior in AG-GP rats (P treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  20. Behavior problems at ages 6 and 11 and high school academic achievement: longitudinal latent variable modeling.

    Science.gov (United States)

    Breslau, Naomi; Breslau, Joshua; Miller, Elizabeth; Raykov, Tenko

    2011-02-28

    Previous studies documented long-run effects of behavior problems at the start of school on academic achievement. However, these studies did not examine whether the observed effects of early behavior problems are explained by more proximate behavior problems, given the tendency of children's behavior problems to persist. Latent variable modeling was applied to estimate the effects of behavior problems at ages 6 and 11 on academic achievement at age 17, using data from a longitudinal study (n=823). Behavior problems at ages 6 and 11, each stage independently of the other, predicted lower math and reading test scores at age 17, controlling for intelligence quotient (IQ), birth weight, maternal characteristics, family and community environment, and taking into account behavior problems at age 17. Behavior problems at the start of school, independent of later behavior problems, exert lingering effects on achievement by impeding the acquisition of cognitive skills that are the foundation for later academic progress.

  1. Rotating Stellar Models Can Account for the Extended Main Sequence Turnoffs in Intermediate Age Clusters

    CERN Document Server

    Brandt, Timothy D

    2015-01-01

    We show that the extended main sequence turnoffs seen in intermediate age Large Magellanic Cloud (LMC) clusters, often attributed to age spreads of several hundred Myr, may be easily accounted for by variable stellar rotation in a coeval population. We compute synthetic photometry for grids of rotating stellar evolution models and interpolate them to produce isochrones at a variety of rotation rates and orientations. An extended main sequence turnoff naturally appears in color-magnitude diagrams at ages just under 1 Gyr, peaks in extent between ~1 and 1.5 Gyr, and gradually disappears at around 2 Gyr in age. We then fit our interpolated isochrones by eye to four LMC clusters with very extended main sequence turnoffs: NGC 1783, 1806, 1846, and 1987. In each case, stellar populations with a single age and metallicity can comfortably account for the observed extent of the turnoff region.

  2. Developmental trajectories of verbal and visuospatial abilities in healthy older adults: comparison of the hemisphere asymmetry reduction in older adults model and the right hemi-ageing model.

    Science.gov (United States)

    Hatta, Takeshi; Iwahara, Akihiko; Hatta, Taketoshi; Ito, Emi; Hatta, Junko; Hotta, Chie; Nagahara, Naoko; Fujiwara, Kazumi; Hamajima, Nobuyuki

    2015-01-01

    Two models of cognitive ageing, the hemisphere asymmetry reduction in older adults (HAROLD) model and the right hemi-ageing model, were compared based upon the verbal memory and visuospatial task performance of 338 elderly participants. Comparison of the developmental trajectories for four age groups (50s, 60s, 70s and 80s) supported the HAROLD model, but not the right hemi-ageing model. Performance differences between the verbal memory and visuospatial tasks in the earlier age groups decreased in the later age groups. There was a sex difference in the cognitive-decline trajectories for verbal and visuospatial task performance after the 50s.

  3. Forecasting Age-Specific Brain Cancer Mortality Rates Using Functional Data Analysis Models

    Directory of Open Access Journals (Sweden)

    Keshav P. Pokhrel

    2015-01-01

    Full Text Available Incidence and mortality rates are considered as a guideline for planning public health strategies and allocating resources. We apply functional data analysis techniques to model age-specific brain cancer mortality trend and forecast entire age-specific functions using exponential smoothing state-space models. The age-specific mortality curves are decomposed using principal component analysis and fit functional time series model with basis functions. Nonparametric smoothing methods are used to mitigate the existing randomness in the observed data. We use functional time series model on age-specific brain cancer mortality rates and forecast mortality curves with prediction intervals using exponential smoothing state-space model. We also present a disparity of brain cancer mortality rates among the age groups together with the rate of change of mortality rates. The data were obtained from the Surveillance, Epidemiology and End Results (SEER program of the United States. The brain cancer mortality rates, classified under International Classification Disease code ICD-O-3, were extracted from SEER*Stat software.

  4. Spectral ageing in the era of big data: integrated versus resolved models

    Science.gov (United States)

    Harwood, Jeremy J.

    2017-04-01

    Continuous injection models of spectral ageing have long been used to determine the age of radio galaxies from their integrated spectrum; however, many questions about their reliability remain unanswered. With various large area surveys imminent (e.g. LOw Frequency ARray, MeerKAT, Murchison Widefield Array) and planning for the next generation of radio interferometers are well underway (e.g. next generation VLA, Square Kilometre Array), investigations of radio galaxy physics are set to shift away from studies of individual sources to the population as a whole. Determining if and how integrated models of spectral ageing can be applied in the era of big data is therefore crucial. In this paper, I compare classical integrated models of spectral ageing to recent well-resolved studies that use modern analysis techniques on small spatial scales to determine their robustness and validity as a source selection method. I find that integrated models are unable to recover key parameters and, even when known a priori, provide a poor, frequency-dependent description of a source's spectrum. I show a disparity of up to a factor of 6 in age between the integrated and resolved methods but suggest, even with these inconsistencies, such models still provide a potential method of candidate selection in the search for remnant radio galaxies and in providing a cleaner selection of high redshift radio galaxies in z - α selected samples.

  5. Observational Constraints on Interacting Model of New Agegraphic Dark Energy and Alleviation of Cosmic Age Problem

    CERN Document Server

    Li, Yun-He; Cui, Jing-Lei; Wang, Zhuo; Zhang, Xin

    2010-01-01

    Many dark energy models fail to pass the cosmic age test via the old quasar APM 08279+5255 at redshift $z=3.91$, even the $\\Lambda$CDM model and the holographic dark energy model are not exception. In this paper, we focus on the topic of age problem in the new agegraphic dark energy (NADE) model. We determine the age of the universe in the NADE model by using the fitting result of observational data including type Ia supernovae (SNIa), baryon acoustic oscillation (BAO) and cosmic microwave background (CMB). It is shown that the NADE model also faces the challenge of the age problem caused by the old quasar APM 08279+5255. In order to overcome such a difficulty, we consider the possible interaction between dark energy and matter. We show that the old quasar APM 08279+5255 at redshift $z=3.91$ can be successfully accommodated in the interacting new agegraphic dark energy (INADE) model at $2\\sigma$ level under the current observational constraints.

  6. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    OpenAIRE

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rat...

  7. Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling.

    Science.gov (United States)

    Nagase, Takashi; Akase, Tomoko; Sanada, Hiromi; Minematsu, Takeo; Ibuki, Ai; Huang, Lijuan; Asada, Mayumi; Yoshimura, Kotaro; Nagase, Miki; Shimada, Tsutomu; Aburada, Masaki; Nakagami, Gojiro; Sugama, Junko

    2013-02-01

    Aging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging-like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging-like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV-evoked aging-like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging-like skin in the UV-irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging-like changes in the skin. The 2-week UV onto the non-MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.

  8. Characterizing cognitive aging of working memory and executive function in animal models.

    Science.gov (United States)

    Bizon, Jennifer L; Foster, Thomas C; Alexander, Gene E; Glisky, Elizabeth L

    2012-01-01

    Executive functions supported by prefrontal cortical (PFC) systems provide essential control and planning mechanisms to guide goal-directed behavior. As such, age-related alterations in executive functions can mediate profound and widespread deficits on a diverse array of neurocognitive processes. Many of the critical neuroanatomical and functional characteristics of prefrontal cortex are preserved in rodents, allowing for meaningful cross species comparisons relevant to the study of cognitive aging. In particular, as rodents lend themselves to genetic, cellular and biochemical approaches, rodent models of executive function stand to significantly contribute to our understanding of the critical neurobiological mechanisms that mediate decline of executive processes across the lifespan. Moreover, rodent analogs of executive functions that decline in human aging represent an essential component of a targeted, rational approach for developing and testing effective treatment and prevention therapies for age-related cognitive decline. This paper reviews behavioral approaches used to study executive function in rodents, with a focus on those assays that share a foundation in the psychological and neuroanatomical constructs important for human aging. A particular emphasis is placed on behavioral approaches used to assess working memory and cognitive flexibility, which are sensitive to decline with age across species and for which strong rodent models currently exist. In addition, other approaches in rodent behavior that have potential for providing analogs to functions that reliably decline to human aging (e.g., information processing speed) are discussed.

  9. Modeling variations of marine reservoir ages during the last 45 000 years

    Directory of Open Access Journals (Sweden)

    J. Franke

    2008-01-01

    Full Text Available When dating marine samples with 14C, the reservoir-age effect is usually assumed to be constant, although atmospheric 14C production rate and ocean circulation changes cause temporal and spatial reservoir-age variations. These lead to dating errors, which can limit the interpretation of cause and effect in paleoclimate data. We used a global ocean circulation model forced by transient atmospheric Δ14C variations to calculate reservoir ages for the last 45 000 years for a present day-like and a last glacial maximum-like ocean circulation. A ~30% reduced Atlantic meridonal overturning circulation leads to increased reservoir ages by up to ~500 years in high latitudes. Temporal variations are proportional to the absolute value of the reservoir age; regions with large reservoir age also show large variation. Temporal variations range between ~300 years in parts of the subtropics and ~1000 years in the Southern Ocean. For tropical regions, which are generally assumed to have nearly stable reservoir ages, the model suggests variations of several hundred years.

  10. Characterizing Cognitive Aging of Working Memory and Executive Function in Animal Models

    Directory of Open Access Journals (Sweden)

    Jennifer Lynn Bizon

    2012-09-01

    Full Text Available Executive functions supported by prefrontal cortical systems provide essential control and planning mechanisms to guide goal-directed behavior. As such, age-related alterations in executive functions can mediate profound and widespread deficits on a diverse array of neurocognitive processes. Many of the critical neuroanatomical and functional characteristics of prefrontal cortex are preserved in rodents, allowing for meaningful cross-species comparisons relevant to the study of cognitive aging. In particular, as rodents lend themselves to genetic, cellular and biochemical approaches, rodent models of executive function stand to significantly contribute to our understanding of the critical neurobiological mechanisms that mediate decline of executive processes across the lifespan. Moreover, rodent analogues of executive functions that decline in human aging represent an essential component of a targeted, rational approach for developing and testing effective treatment and prevention therapies for age-related cognitive decline. This paper reviews behavioral approaches used to study executive function in rodents, with a focus on those assays that share a foundation in the psychological and neuroanatomical constructs important for human aging. A particular emphasis is placed on behavioral approaches used to assess working memory and cognitive flexibility, which are sensitive to decline with age across species and for which strong rodent models currently exist. In addition, other approaches in rodent behavior that have potential for providing analogues to functions that reliably decline to human aging (e.g., information processing speed are discussed.

  11. Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance.

    Science.gov (United States)

    van Beek, Johannes H G M; Kirkwood, Thomas B L; Bassingthwaighte, James B

    2016-04-01

    Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease.

  12. Asteroid age distributions determined by space weathering and collisional evolution models

    CERN Document Server

    Willman, Mark; 10.1016/j.icarus.2010.02.017

    2010-01-01

    We provide evidence of consistency between the dynamical evolution of main belt asteroids and their color evolution due to space weathering. The dynamical age of an asteroid's surface \\citep{bib.bot05a,bib.nes05} is the time since its last catastrophic disruption event which is a function of the object's diameter. The age of an S-complex asteroid's surface may also be determined from its color using a space weathering model \\citep[e.g.][]{bib.wil10,bib.jed04,bib.wil08,bib.mar06}. We used a sample of 95 S-complex asteroids from SMASS and obtained their absolute magnitudes and $u,g,r,i,z$ filter magnitudes from SDSS. The absolute magnitudes yield a size-derived age distribution. The $u,g,r,i,z$ filter magnitudes lead to the principal component color which yields a color-derived age distribution by inverting our color-age relationship, an enhanced version of the `dual $\\tau$' space weathering model of \\citet{bib.wil10}. We fit the size-age distribution to the enhanced dual $\\tau$ model and found characteristic w...

  13. Evaluation of Aged Garlic Extract Neuroprotective Effect in a Focal Model of Cerebral Ischemia

    Science.gov (United States)

    Aguilera, Penélope; Maldonado, Perla D.; Ortiz-Plata, Alma; Barrera, Diana; Chánez-Cárdenas, María Elena

    2008-02-01

    The oxidant species generated in cerebral ischemia have been implicated as important mediators of neuronal injury through damage to lipids, DNA, and proteins. Since ischemia as well as reperfusion insults generate oxidative stress, the administration of antioxidants may limit oxidative damage and ameliorate disease progression. The present work shows the transitory neuroprotective effect of the aged garlic extract (AGE) administration (a proposed antioxidant compound) in a middle cerebral artery occlusion (MCAO) model in rats and established its therapeutic window. To determine the optimal time of administration, animal received AGE (1.2 mL/kg) intraperitoneally 30 min before onset of reperfusion (-0.5 R), at the beginning of reperfusion (0R), or 1 h after onset of reperfusion (1R). Additional doses were administrated after 1, 2, or 3 h after onset of reperfusion. To establish the therapeutic window of AGE, the infarct area was determined for each treatment after different times of reperfusion. Results show that the administration of AGE at the onset of reperfusion reduced the infarct area by 70% (evaluated after 2 h reperfusion). The therapeutic window of AGE was determined. Repeated doses did not extend the temporal window of protection. A significant reduction in the nitrotyrosine level was observed in the brain tissue subjected to MCAO after AGE treatment at the onset of reperfusion. Data in the present work show that AGE exerts a transitory neuroprotective effect in response to ischemia/reperfusion-induced neuronal injury.

  14. Modeling transient groundwater age in the Middle Wairarapa Valley, New Zealand

    Science.gov (United States)

    Evison, R.; Daughney, C.; Jackson, B. M.; Toews, M. W.; Cornaton, F. J.; Gyopari, M.; McAllister, D.

    2013-12-01

    Age information provides insights into groundwater flow and transport processes and thus enables better groundwater management. It is accepted that groundwater is composed of a mixture of water with different ages. For example, a groundwater sample with an old mean age may still contain a fraction of young water; recent contamination is therefore a potential risk that may not be conveyed by consideration of the mean age alone. This project focuses on catchment-scale evaluation of the full distribution of groundwater age as a function of space and time in the 270 km2 Middle Wairarapa Valley, New Zealand. The Wairarapa Valley exhibits complex interactions between its rivers and shallow aquifers. Agriculture is an integral part of the region with widespread irrigation and nutrient application. This requires effective regional management due to the risk of contamination and depletion of groundwater reservoirs. The starting point was a transient finite-element groundwater flow model originally developed by Greater Wellington Regional Council (GWRC). The GWRC flow model was converted to simulate transport of the age tracer tritium using Ground Water (GW) software. There are several techniques to calibrate groundwater models and assess appropriate parameter values, all of which have the problem of non-uniqueness. In this study the Gauss-Marquardt-Levenberg method was utilized to calibrate the model (through PEST), but in order to increase robustness, a classic Monte Carlo method with uniform random sampling was also used to sample the domain's global range of flow and transport parameters. This provided an increased measure of confidence in model output, as the global range of parameter values could be explored, which is not achieved via the localized Gauss-Marquardt-Levenberg parameter estimation scheme. The calibration objective with both methods used least squares minimization between the simulated and observed hydraulic head levels and tritium concentrations. GW

  15. Aging and percolation dynamics in a Non-Poissonian temporal network model.

    Science.gov (United States)

    Moinet, Antoine; Starnini, Michele; Pastor-Satorras, Romualdo

    2016-08-01

    We present an exhaustive mathematical analysis of the recently proposed Non-Poissonian Activity Driven (NoPAD) model [Moinet et al., Phys. Rev. Lett. 114, 108701 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.108701], a temporal network model incorporating the empirically observed bursty nature of social interactions. We focus on the aging effects emerging from the non-Poissonian dynamics of link activation, and on their effects on the topological properties of time-integrated networks, such as the degree distribution. Analytic expressions for the degree distribution of integrated networks as a function of time are derived, exploring both limits of vanishing and strong aging. We also address the percolation process occurring on these temporal networks, by computing the threshold for the emergence of a giant connected component, highlighting the aging dependence. Our analytic predictions are checked by means of extensive numerical simulations of the NoPAD model.

  16. A Novel Statistical Model for Water Age Estimation in Water Distribution Networks

    Directory of Open Access Journals (Sweden)

    Wei-ping Cheng

    2015-01-01

    Full Text Available The water retention time in the water distribution network is an important indicator for water quality. The water age fluctuates with the system demand. The residual chlorine concentration varies with the water age. In general, the concentration of residual chlorine is linearly dependent on the water demand. A novel statistical model using monitoring data of residual chlorine to estimate the nodal water age in water distribution networks is put forward in the present paper. A simplified two-step procedure is proposed to solve this statistical model. It is verified by two virtual systems and a practical application to analyze the water distribution system of Hangzhou city, China. The results agree well with that from EPANET. The model provides a low-cost and reliable solution to evaluate the water retention time.

  17. A behavioral stages model of classical (Pavlovian) conditioning: application to cognitive aging.

    Science.gov (United States)

    Powell, D A

    1999-01-01

    In the present article, it is argued that a five-stage sequential model of the behavioral and neurophysiological events that occur when organisms are exposed to signals predicting significant events suggests that classical conditioning produces multiple memory traces involving both excitatory and inhibitory processes. Further, these multiple brain structures and associated neurophysiological mechanisms are beginning to be understood; thus, using Pavlovian conditioning techniques to study aging and cognitive functions may provide insights into which brain structures or mechanisms are responsible for more general age-related declines in associative learning and memory. The evidence for this model is briefly reviewed and studies suggesting age-related effects on classical conditioning of various response systems are described within the context of the brain structures implicated by the model.

  18. Nrf2 Signaling and the Slowed Aging Phenotype: Evidence from Long-Lived Models

    Directory of Open Access Journals (Sweden)

    Danielle R. Bruns

    2015-01-01

    Full Text Available Studying long-lived animals provides novel insight into shared characteristics of aging and represents a unique model to elucidate approaches to prevent chronic disease. Oxidant stress underlies many chronic diseases and resistance to stress is a potential mechanism governing slowed aging. The transcription factor nuclear factor (erythroid-derived 2-like 2 is the “master regulator” of cellular antioxidant defenses. Nrf2 is upregulated by some longevity promoting interventions and may play a role in regulating species longevity. However, Nrf2 expression and activity in long-lived models have not been well described. Here, we review evidence for altered Nrf2 signaling in a variety of slowed aging models that accomplish lifespan extension via pharmacological, nutritional, evolutionary, genetic, and presumably epigenetic means.

  19. Aging and percolation dynamics in a Non-Poissonian temporal network model

    Science.gov (United States)

    Moinet, Antoine; Starnini, Michele; Pastor-Satorras, Romualdo

    2016-08-01

    We present an exhaustive mathematical analysis of the recently proposed Non-Poissonian Activity Driven (NoPAD) model [Moinet et al., Phys. Rev. Lett. 114, 108701 (2015), 10.1103/PhysRevLett.114.108701], a temporal network model incorporating the empirically observed bursty nature of social interactions. We focus on the aging effects emerging from the non-Poissonian dynamics of link activation, and on their effects on the topological properties of time-integrated networks, such as the degree distribution. Analytic expressions for the degree distribution of integrated networks as a function of time are derived, exploring both limits of vanishing and strong aging. We also address the percolation process occurring on these temporal networks, by computing the threshold for the emergence of a giant connected component, highlighting the aging dependence. Our analytic predictions are checked by means of extensive numerical simulations of the NoPAD model.

  20. Aging and percolation dynamics in a Non-Poissonian temporal network model

    CERN Document Server

    Moinet, Antoine; Pastor-Satorras, Romualdo

    2016-01-01

    We present an exhaustive mathematical analysis of the recently proposed Non-Poissonian Ac- tivity Driven (NoPAD) model [Moinet et al. Phys. Rev. Lett., 114 (2015)], a temporal network model incorporating the empirically observed bursty nature of social interactions. We focus on the aging effects emerging from the Non-Poissonian dynamics of link activation, and on their effects on the topological properties of time-integrated networks, such as the degree distribution. Analytic expressions for the degree distribution of integrated networks as a function of time are derived, ex- ploring both limits of vanishing and strong aging. We also address the percolation process occurring on these temporal networks, by computing the threshold for the emergence of a giant connected component, highlighting the aging dependence. Our analytic predictions are checked by means of extensive numerical simulations of the NoPAD model.

  1. Prediction of Age at Menopause in Women of Suburban Areas in Chennai Using A Model of Fsh Over Age - A Pilot Study

    Directory of Open Access Journals (Sweden)

    SM Priyadharshini

    2014-02-01

    Full Text Available Objectives: The human ovary is characterized by early senescence and the end stage of ovarian activity is termed menopause. The age at which menopause occur is between 45 and 55 years world wide. The objective of this pilot study is to determine the age at menopause by using a model of FSH over age in women of sub urban region around Chennai, India. Materials and Methods: The subjects include 500 patients of age between 30 and 36 yrs with BMI ranging from 24-28.After recording their general profile and history, blood samples were obtained by venipuncture and hormone FSH was estimated on the day 3 of the menstrual cycle. Based on functional dependence of FSH in the form of exponential relation with age, a model was proposed. Using least square approximation the beta values were calculated. Results: With the help of beta values and using the cut off value of 40 IU/ml for FSH, this predicted model determined the age of menopause as 44.6yrs in women of sub urban region around Chennai. Conclusion: The age of menopause is different in various region worlds wide. According to this pilot study the suburban women of Chennai, attain menopause at an age of 44.6 years. Further exploration should be done to alleviate the role of diet, life style and ethnic variation on menopausal age and the impact of chronic disease like osteoporosis during the period of menopause.

  2. Modeling the Impact of Uganda's Safe Male Circumcision Program: Implications for Age and Regional Targeting.

    Directory of Open Access Journals (Sweden)

    Katharine Kripke

    Full Text Available Uganda aims to provide safe male circumcision (SMC to 80% of men ages 15-49 by 2016. To date, only 2 million men have received SMC of the 4.2 million men required. In response to age and regional trends in SMC uptake, the country sought to re-examine its targets with respect to age and subnational region, to assess the program's progress, and to refine the implementation approach.The Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0, was used in conjunction with incidence projections from the Spectrum/AIDS Impact Module (AIM to conduct this analysis. Population, births, deaths, and HIV incidence and prevalence were used to populate the model. Baseline male circumcision prevalence was derived from the 2011 AIDS Indicator Survey. Uganda can achieve the most immediate impact on HIV incidence by circumcising men ages 20-34. This group will also require the fewest circumcisions for each HIV infection averted. Focusing on men ages 10-19 will offer the greatest impact over a 15-year period, while focusing on men ages 15-34 offers the most cost-effective strategy over the same period. A regional analysis showed little variation in cost-effectiveness of scaling up SMC across eight regions. Scale-up is cost-saving in all regions. There is geographic variability in program progress, highlighting two regions with low baseline rates of circumcision where additional efforts will be needed.Focusing SMC efforts on specific age groups and regions may help to accelerate Uganda's SMC program progress. Policy makers in Uganda have already used model outputs in planning efforts, proposing males ages 10-34 as a priority group for SMC in the 2014 application to the Global Fund's new funding model. As scale-up continues, the country should also consider a greater effort to expand SMC in regions with low MC prevalence.

  3. Model calculations of the age of firn air across the Antarctic continent

    Directory of Open Access Journals (Sweden)

    K. A. Kaspers

    2004-01-01

    Full Text Available The age of firn air in Antarctica at pore close-off depth is only known for a few specific sites where firn air has been sampled for analyses. We present a model that calculates the age of firn air at pore close-off depth for the entire Antarctic continent. The model basically uses four meteorological parameters as input (surface temperature, pressure, accumulation rate and wind speed. Using parameterisations for surface snow density, pore close-off density and tortuosity, in combination with a density-depth model and data of a regional atmospheric climate model, distribution of pore close-off depth for the entire Antarctic continent is determined. The deepest pore close-off depth was found for the East Antarctic Plateau near 72° E, 82° S, at 150±15 m (2σ. A firn air diffusion model was applied to calculate the age of CO2 at pore close-off depth. The results predict that the oldest firn gas (CO2 age is located between Dome Fuji, Dome Argos and Vostok at 43° E, 78° S being 148±23 (1σ or 38 for 2σ years old. At this location an atmospheric trace gas record should be obtained. In this study we show that methyl chloride could be recorded with a predicted length of 125 years as an example for trace gas records at this location. The longest record currently available from firn air is derived at South Pole, being 80 years. Sensitivity tests reveal that the locations with old firn air (East Antarctic Plateau have an estimated uncertainty (2σ for the modelled CO2 age at pore close-off depth of 30% and of about 40% for locations with younger firn air (CO2 age typically 40 years. Comparing the modelled age of CO2 at pore close-off depth with directly determined ages at seven sites yielded a correlation coefficient of 0.90 and a slope close to 1, suggesting a high level of confidence for the modelled results in spite of considerable remaining uncertainties.

  4. Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal models of Parkinson's disease.

    Science.gov (United States)

    Tamás, Andrea; Lubics, Andrea; Lengvári, István; Reglodi, Dóra

    2006-04-01

    The effects of aging and gender on the neurochemistry of the dopaminergic system have been studied extensively; however, data on comparative behavioral consequences of lesions of the dopaminergic system in aging and in female animals are limited. This study presents experimental results on the behavioral and morphological outcome in young, aging, and gonadectomized male and female rats in the 6-OHDA model of Parkinson's disease. Both young and aging male animals were more susceptible to 6-OHDA than females: female rats had significantly less dopaminergic cell loss and showed a higher degree of behavioral recovery. Although the dopaminergic cell loss was only slightly more in the aging rats of the same sex, they showed more severe behavioral deficits in both gender groups. Ovariectomy did not significantly influence the dopaminergic cell loss, but behavioral recovery was worse when compared to non-ovariectomized females. In contrast, castrated males had significantly less dopaminergic cell loss than non-castrated males, but the behavioral recovery was not significantly better. The obtained results are discussed in light of the available literature on the age and gender differences in animals models of Parkinson's disease.

  5. 230Th-234U Model-Ages of Some Uranium Standard Reference Materials

    Energy Technology Data Exchange (ETDEWEB)

    Williams, R W; Gaffney, A M; Kristo, M J; Hutcheon, I D

    2009-05-28

    The 'age' of a sample of uranium is an important aspect of a nuclear forensic investigation and of the attribution of the material to its source. To the extent that the sample obeys the standard rules of radiochronometry, then the production ages of even very recent material can be determined using the {sup 230}Th-{sup 234}U chronometer. These standard rules may be summarized as (a) the daughter/parent ratio at time=zero must be known, and (b) there has been no daughter/parent fractionation since production. For most samples of uranium, the 'ages' determined using this chronometer are semantically 'model-ages' because (a) some assumption of the initial {sup 230}Th content in the sample is required and (b) closed-system behavior is assumed. The uranium standard reference materials originally prepared and distributed by the former US National Bureau of Standards and now distributed by New Brunswick Laboratory as certified reference materials (NBS SRM = NBL CRM) are good candidates for samples where both rules are met. The U isotopic standards have known purification and production dates, and closed-system behavior in the solid form (U{sub 3}O{sub 8}) may be assumed with confidence. We present here {sup 230}Th-{sup 234}U model-ages for several of these standards, determined by isotope dilution mass spectrometry using a multicollector ICP-MS, and compare these ages with their known production history.

  6. Structural modeling of age specific fertility curves in Peninsular Malaysia: An approach of Lee Carter method

    Science.gov (United States)

    Hanafiah, Hazlenah; Jemain, Abdul Aziz

    2013-11-01

    In recent years, the study of fertility has been getting a lot of attention among research abroad following fear of deterioration of fertility led by the rapid economy development. Hence, this study examines the feasibility of developing fertility forecasts based on age structure. Lee Carter model (1992) is applied in this study as it is an established and widely used model in analysing demographic aspects. A singular value decomposition approach is incorporated with an ARIMA model to estimate age specific fertility rates in Peninsular Malaysia over the period 1958-2007. Residual plots is used to measure the goodness of fit of the model. Fertility index forecast using random walk drift is then utilised to predict the future age specific fertility. Results indicate that the proposed model provides a relatively good and reasonable data fitting. In addition, there is an apparent and continuous decline in age specific fertility curves in the next 10 years, particularly among mothers' in their early 20's and 40's. The study on the fertility is vital in order to maintain a balance between the population growth and the provision of facilities related resources.

  7. Efficient Workflows for Curation of Heterogeneous Data Supporting Modeling of U-Nb Alloy Aging

    Energy Technology Data Exchange (ETDEWEB)

    Ward, Logan Timothy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hackenberg, Robert Errol [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-31

    These are slides from a presentation summarizing a graduate research associate's summer project. The following topics are covered in these slides: data challenges in materials, aging in U-Nb Alloys, Building an Aging Model, Different Phase Trans. in U-Nb, the Challenge, Storing Materials Data, Example Data Source, Organizing Data: What is a Schema?, What does a "XML Schema" look like?, Our Data Schema: Nice and Simple, Storing Data: Materials Data Curation System (MDCS), Problem with MDCS: Slow Data Entry, Getting Literature into MDCS, Staging Data in Excel Document, Final Result: MDCS Records, Analyzing Image Data, Process for Making TTT Diagram, Bottleneck Number 1: Image Analysis, Fitting a TTP Boundary, Fitting a TTP Curve: Comparable Results, How Does it Compare to Our Data?, Image Analysis Workflow, Curating Hardness Records, Hardness Data: Two Key Decisions, Before Peak Age? - Automation, Interactive Viz, Which Transformation?, Microstructure-Informed Model, Tracking the Entire Process, General Problem with Property Models, Pinyon: Toolkit for Managing Model Creation, Tracking Individual Decisions, Jupyter: Docs and Code in One File, Hardness Analysis Workflow, Workflow for Aging Models, and conclusions.

  8. A four-component model of age-related memory change.

    Science.gov (United States)

    Healey, M Karl; Kahana, Michael J

    2016-01-01

    We develop a novel, computationally explicit, theory of age-related memory change within the framework of the context maintenance and retrieval (CMR2) model of memory search. We introduce a set of benchmark findings from the free recall and recognition tasks that include aspects of memory performance that show both age-related stability and decline. We test aging theories by lesioning the corresponding mechanisms in a model fit to younger adult free recall data. When effects are considered in isolation, many theories provide an adequate account, but when all effects are considered simultaneously, the existing theories fail. We develop a novel theory by fitting the full model (i.e., allowing all parameters to vary) to individual participants and comparing the distributions of parameter values for older and younger adults. This theory implicates 4 components: (a) the ability to sustain attention across an encoding episode, (b) the ability to retrieve contextual representations for use as retrieval cues, (c) the ability to monitor retrievals and reject intrusions, and (d) the level of noise in retrieval competitions. We extend CMR2 to simulate a recognition memory task using the same mechanisms the free recall model uses to reject intrusions. Without fitting any additional parameters, the 4-component theory that accounts for age differences in free recall predicts the magnitude of age differences in recognition memory accuracy. Confirming a prediction of the model, free recall intrusion rates correlate positively with recognition false alarm rates. Thus, we provide a 4-component theory of a complex pattern of age differences across 2 key laboratory tasks.

  9. Preclinical models of stroke in aged animals with or without comorbidities: role of neuroinflammation.

    Science.gov (United States)

    Buga, A-M; Di Napoli, Mario; Popa-Wagner, A

    2013-12-01

    Age is the principal nonmodifiable risk factor for stroke. Over the past 10 years, suitable models for stroke in aged rats have been established. At genetic and cellular level there are significant differences in behavioral, cytological and genomics responses to injury in old animals as compared with the young ones. Behaviorally, the aged rats have the capacity to recover after cortical infarcts albeit to a lower extent than the younger counterparts. Similarly, the increased vulnerability of the aged brain to stroke, together with a decreased interhemisphere synchrony after stroke, assessed by different experimental methods (MRI, fMRI, in vivo microscopy, EEG) leads to unfavorable recovery of physical and cognitive functions in aged people and may have a prognostic value for the recovery of stroke patients. Furthermore, in elderly, comorbidities like diabetes or arterial hypertension are associated with higher risk of stroke, increased mortality and disability, and poorer functional status and quality of life. Aging brain reacts strongly to ischemia-reperfusion injury with an early inflammatory response. The process of cellular senescence can be an important additional contributor to chronic post-stroke by creating a "primed" inflammatory environment in the brain. Overall, these pro-inflammatory reactions promote early scar formation associated with tissue fibrosis and reduce functional recovery. A better understanding of molecular factors and signaling pathways underlying the contribution of comorbidities to stroke-induced pathological sequelae, may be translated into successful treatment or prevention therapies for age-associated diseases which would improve lifespan and quality of life.

  10. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Rezvanfar

    2014-01-01

    Full Text Available There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS. Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO and reactive oxygen species (ROS and decrease in total antioxidant capacity (TAC in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α levels, and ovarian matrix metalloproteinase-2 (MMP-2 were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.

  11. Analysis of an Age Structured SEIRS Epidemic Model with Varying Total Population Size and Vaccination

    Institute of Scientific and Technical Information of China (English)

    Xue-Zhi Li; Geni Gupur; Guang-Tian Zhu

    2004-01-01

    This article focuses on the study of an age structured SEIRS epidemic model with a vaccination program when the total population size is not kept at constant. We first give the explicit expression of the reproduction number R((ψ),(λ))in the presence of vaccine((λ))is the exponent of growth of total population), and show that the infection-free steady state is linearly stable if R ((ψ),(λ))1, then we apply the theoretical results to vaccination policies to determine the optimal age or ages at which an individual should be vaccinated. It is shown that the optimal strategy can be either one-or two-age strategies.

  12. A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

    Directory of Open Access Journals (Sweden)

    Conor Lawless

    Full Text Available Increases in cellular Reactive Oxygen Species (ROS concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage. However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS. We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

  13. Active Aging for Individuals with Parkinson’s Disease: Definitions, Literature Review, and Models

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammad Fereshtehnejad

    2014-01-01

    Full Text Available Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson’s disease (PD. The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson’s Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging.

  14. Arterial pulse pressure amplification described by means of a nonlinear wave model: characterization of human aging

    Science.gov (United States)

    Alfonso, M.; Cymberknop, L.; Armentano, R.; Pessana, F.; Wray, S.; Legnani, W.

    2016-04-01

    The representation of blood pressure pulse as a combination of solitons captures many of the phenomena observed during its propagation along the systemic circulation. The aim of this work is to analyze the applicability of a compartmental model for propagation regarding the pressure pulse amplification associated with arterial aging. The model was applied to blood pressure waveforms that were synthesized using solitons, and then validated by waveforms obtained from individuals from differentiated age groups. Morphological changes were verified in the blood pressure waveform as a consequence of the aging process (i.e. due to the increase in arterial stiffness). These changes are the result of both a nonlinear interaction and the phenomena present in the propagation of nonlinear mechanic waves.

  15. Anti-apoptotic treatment in mouse models of age-related hearing loss

    Institute of Scientific and Technical Information of China (English)

    Fengchan Han; Oumei Wang; Quanxiang Cai

    2016-01-01

    Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear. Although the mechanisms leading to genetic hearing loss are not completely understood, caspase-family proteases function as important signals in the inner ear pathology. It is now accepted that mouse models are the best tools to study the mechanism of genetic hearing loss or AHL. Here, we provide a brief review of recent studies on hearing improvement in mouse models of AHL by anti-apoptotic treatment.

  16. Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity

    DEFF Research Database (Denmark)

    Tan, Qihua; Bathum, L; Christiansen, L

    2003-01-01

    In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic...... situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture...

  17. An alternative Cattell-Horn-Carroll (CHC) factor structure of the WAIS-IV: age invariance of an alternative model for ages 70-90.

    Science.gov (United States)

    Niileksela, Christopher R; Reynolds, Matthew R; Kaufman, Alan S

    2013-06-01

    The Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV) is by the far the most popular intelligence test for the assessment of adults in clinical and neuropsychological practice. Despite a number of studies examining the factor structure of the WAIS-IV from a Cattell-Horn-Carroll (CHC) perspective (Benson, Hulac, & Kranzler, 2010; Ward, Bergman, & Hebert, 2012), a CHC interpretation of the WAIS-IV for individuals ages 70 and above has been absent from the literature. The exclusion of individuals ages 70 and above in previous research is likely due to the absence of several key supplemental subtests used to create a full CHC model. We provide an alternative five-factor CHC model of the WAIS-IV which includes only the subtests administered to individuals ages 70 and above in the standardization sample. Our results show (a) the alternative CHC model fits the data well; (b) this alternative CHC model met criteria for partial strict measurement invariance across the life span (only Similarities showed noninvariance) using strict criteria; (c) the five factors for ages 70-90 measure the same five CHC broad abilities identified in previous analyses reported for ages 16-69; and (d) the five-factor CHC solution for ages 70-90 is valid for the entire WAIS-IV age range and can be used whenever examiners administer the core battery but opt not to administer supplemental subtests.

  18. Cyclostratigraphy for Chinese red clay sequences: Implications to changing previous age models and paleoclimate interpretations

    Science.gov (United States)

    Anwar, T.; Kravchinsky, V. A.; Zhang, R.

    2015-12-01

    The Chinese Loess Plateau contains red clay sequence which has continuous alternation of sedimentary cycles with recurrent paleoclimatic fluctuations. Absence of abundant fossils and inability of radiometric dating method made magnetostratigraphy a leading method to build age model for the red clay. Here magnetostratigraphic age model in red clay sequence is tested using cyclostratigraphy as orbital parameters of Earth are known. Milankovitch periodicities recorded in magnetic susceptibility and grain size in the Shilou red clay section are investigated and previously found age of 11 Ma for this section is re-evaluated. Magnetostratigraphy dating based on only visual correlation could potentially lead to erroneous age model. In this study the correlation is executed through the iteration procedure until it is supported by cyclostratigraphy; i.e. Milankovitch cycles are resolved in the best possible manner. Our new approach provides an age of 5.2 Ma for the Shilou profile. Wavelet analysis reveals that a 400 kyr eccentricity cycle is well preserved and the existence of a 100 kyr eccentricity in the red clay sequence on the eastern Chinese Loess Plateau suggests that eccentricity plays a vital role in Pliocene climate evolution. Paleomonsoon evolution is reconstructed and divided into three intervals (5.2-4.5 Ma, 4.5-3.6 Ma and 3.6-2.58 Ma). The earliest stage indicates that summer and winter monsoon cycles may rapidly alter, whereas the middle stage reflects an intensification of winter monsoon and aridification in Asia, and the youngest stage is characterized by relatively intensified summer monsoon. This study demonstrates that cyclostratigraphy can greatly assist magnetostratigraphy in dating the red clay sequences, and implies that many published age models for the red clay sequences should likely be re-assessed where possible. An evaluation of the monsoon system and climate change in eastern Asia might prominently benefit from this approach.

  19. Infant bone age estimation based on fibular shaft length: model development and clinical validation

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Andy; Stamoulis, Catherine; Bixby, Sarah D.; Breen, Micheal A.; Connolly, Susan A.; Kleinman, Paul K. [Boston Children' s Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2016-03-15

    Bone age in infants (<1 year old) is generally estimated using hand/wrist or knee radiographs, or by counting ossification centers. The accuracy and reproducibility of these techniques are largely unknown. To develop and validate an infant bone age estimation technique using fibular shaft length and compare it to conventional methods. We retrospectively reviewed negative skeletal surveys of 247 term-born low-risk-of-abuse infants (no persistent child protection team concerns) from July 2005 to February 2013, and randomized them into two datasets: (1) model development (n = 123) and (2) model testing (n = 124). Three pediatric radiologists measured all fibular shaft lengths. An ordinary linear regression model was fitted to dataset 1, and the model was evaluated using dataset 2. Readers also estimated infant bone ages in dataset 2 using (1) the hemiskeleton method of Sontag, (2) the hemiskeleton method of Elgenmark, (3) the hand/wrist atlas of Greulich and Pyle, and (4) the knee atlas of Pyle and Hoerr. For validation, we selected lower-extremity radiographs of 114 normal infants with no suspicion of abuse. Readers measured the fibulas and also estimated bone ages using the knee atlas. Bone age estimates from the proposed method were compared to the other methods. The proposed method outperformed all other methods in accuracy and reproducibility. Its accuracy was similar for the testing and validating datasets, with root-mean-square error of 36 days and 37 days; mean absolute error of 28 days and 31 days; and error variability of 22 days and 20 days, respectively. This study provides strong support for an infant bone age estimation technique based on fibular shaft length as a more accurate alternative to conventional methods. (orig.)

  20. Traveling waves and spreading speed on a lattice model with age structure

    Directory of Open Access Journals (Sweden)

    Zongyi Wang

    2012-09-01

    Full Text Available In this article, we study a lattice differential model for a single species with distributed age-structure in an infinite patchy environment. Using method of approaches by Diekmann and Thieme, we develop a comparison principle and construct a suitable sub-solution to the given model, and show that there exists a spreading speed of the system which in fact coincides with the minimal wave speed.

  1. The Use of Mouse Models for Understanding the Biology of Down Syndrome and Aging

    OpenAIRE

    Vacano, Guido N.; Nathan Duval; David Patterson

    2012-01-01

    Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress ...

  2. A Numerical Model for the Thermomechanical Conditions During Hydration of Early-age Concrete

    DEFF Research Database (Denmark)

    Hattel, Jesper; Thorborg, Jesper

    2003-01-01

    In the present study, a macroscopic numerical model for the thermomechanical conditions during hydration of early-age concrete is presented. The formulation is based on a semi-coupled, incremental thermomechanical model where the heat production from the hydration process is expressed in terms of...... analytical solutions are carried out as well as examples of analysis of real concrete structures. (C) 2002 Elsevier Science Inc. All rights reserved....

  3. Age at Marriage as a Mobility Contingency: Estimates for the Nye-Berardo Model

    Science.gov (United States)

    Call, Vaughn R. A.; Otto, Luther B.

    1977-01-01

    This study provides estimates for the Nye and Berardo model of the effect of age at marriage on socioeconomic attainments. The major findings are that marital timing has neither a total effect on educational and occupational attainments, nor does it mediate the total effects of family socioeconomic statuses. (Author)

  4. The "Village" Model: A Consumer-Driven Approach for Aging in Place

    Science.gov (United States)

    Scharlach, Andrew; Graham, Carrie; Lehning, Amanda

    2012-01-01

    Purpose of the Study: This study examines the characteristics of the "Village" model, an innovative consumer-driven approach that aims to promote aging in place through a combination of member supports, service referrals, and consumer engagement. Design and Methods: Thirty of 42 fully operational Villages completed 2 surveys. One survey examined…

  5. Invariance of an Extended Technology Acceptance Model Across Gender and Age Group

    Science.gov (United States)

    Ahmad, Tunku Badariah Tunku; Madarsha, Kamal Basha; Zainuddin, Ahmad Marzuki; Ismail, Nik Ahmad Hisham; Khairani, Ahmad Zamri; Nordin, Mohamad Sahari

    2011-01-01

    In this study, we examined the likelihood of a TAME (extended technology acceptance model), in which the interrelationships among computer self-efficacy, perceived usefulness, intention to use and self-reported use of computer-mediated technology were tested. In addition, the gender- and age-invariant of its causal structure were evaluated. The…

  6. Optimal harvesting for an age-dependent n-dimensional food chain model

    Institute of Scientific and Technical Information of China (English)

    LUO Zhi-xue; DU Ming-yin

    2008-01-01

    This paper is concerned with optimal harvesting policy for an age-dependent n-dimensional food chain model. The existence and uniqueness of non-negative solution of the system are proved using the fixed point theorem. By Mazur's theorem, the existence of optimal control strategy is demonstrated and optimality conditions derived by means of normal cone.

  7. OPTIMAL CONTROL PROBLEM FOR A PERIODIC PREDATOR-PREY MODEL WITH AGE-DEPENDENCE

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In this paper,we investigate optimal policy for periodic predator-prey system with age-dependence.Namely,we consider the model with periodic vital rates and initial distribution.The existence of optimal control strategy is discussed by Mazur's theorem and optimality condition is derived by means of normal cone.

  8. The Hierarchical Factor Model of ADHD: Invariant across Age and National Groupings?

    Science.gov (United States)

    Toplak, Maggie E.; Sorge, Geoff B.; Flora, David B.; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan; Ebstein, Richard; Eisenberg, Jacques; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Thompson, Margaret; Tannock, Rosemary; Asherson, Philip; Faraone, Stephen V.

    2012-01-01

    Objective: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and…

  9. All-Ages Lead Model (Aalm) Version 1.05 (External Draft Report)

    Science.gov (United States)

    The All-Ages Lead Model (AALM) Version 1.05, is an external review draft software and guidance manual. EPA released this software and associated documentation for public review and comment beginning September 27, 2005, until October 27, 2005. The public comments will be accepte...

  10. Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

    Directory of Open Access Journals (Sweden)

    Tracy A. Brennan

    2014-05-01

    Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn

  11. Modelling of Dynamic Strain Aging with a Dislocation-Based Isotropic Hardening Model and Investigation of Orthogonal Loading

    NARCIS (Netherlands)

    Berisha, B.; Hora, P.; Tong, L.; Wahlen, A.; Boogaard, van den A.H.

    2008-01-01

    Based on experimental results, a dislocation material model describing the dynamic strain aging effect at different temperatures is presented. One and two stage loading tests were performed in order to investigate the influence of the loading direction as well as the temperature influence due to the

  12. Transient earth system model simulations as age-scale generators for paleo proxy data?

    Science.gov (United States)

    Timmermann, A.; Stockhecke, M.; Friedrich, T.; Menviel, L.

    2015-12-01

    Generating age models for paleo proxy data can be extremely difficult. Oftentimes assumptions are made which are based on hypothetical relationships between climate and orbital forcings. Whether these relationships (expressed in terms of correlation models) are physically justified and whether they are stationary is testable using transient climate model simulations. Several standard methods to generate age models for paleo-proxy data are scrutinized here, such as orbital tuning and synchronization to benthic stacks. To overcome some of the fundamental weaknesses of these methods we propose to use transient paleo climate model simulations to derive dynamically and physically consistent age models for paleo-proxy data. We illustrate this suggestion using 1) millennial-scale climate variations during MIS 2) orbital-scale climate variability during the past ~800 ka Ad 1) A physically forced MIS3 global hindcast model simulation with an earth system model, designed to match the reconstructed North Atlantic SST variability, can be used to determine the relative timing of different climate and biogeochemical variables at various locations with respect to an initial absolute reference timescale (GICC05 in our case). Corresponding leads and lags are a result of the physical equations of the climate system - not of oversimplisitic statistical assumptions (such as wiggle matching). The key assumption for this approach is that global patterns of Dansgaard-Oeschger variability are caused by centennial to millennial-scale AMOC variability. Ad 2) A transient earth system model simulation of the past ~800 ka is forced with observed greenhouse gas variations (on EDC3), orbital and estimated ice-sheet forcing. Simulated rainfall variations over the Eastern Mediterranean are compared with hydroclimate reconstructions from Lake Van. The simulated rainfall agrees well with the hydroclimate reconstruction (on the MoSto27 timescale) for the first 200 ka. Following this we demonstrate

  13. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model.

    Directory of Open Access Journals (Sweden)

    Daniel Mellem

    Full Text Available Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes.

  14. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model.

    Science.gov (United States)

    Mellem, Daniel; Fischer, Frank; Jaspers, Sören; Wenck, Horst; Rübhausen, Michael

    2016-01-01

    Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes.

  15. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model

    Science.gov (United States)

    Mellem, Daniel; Fischer, Frank; Jaspers, Sören; Wenck, Horst; Rübhausen, Michael

    2016-01-01

    Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes. PMID:26771181

  16. A statistical model for the study of U-Nb aging (u)

    Energy Technology Data Exchange (ETDEWEB)

    Hemphill, Geralyn M [Los Alamos National Laboratory; Hackenberg, Robert E [Los Alamos National Laboratory

    2009-01-01

    This study was undertaken to model the aging response of U-Nb alloys in order to quantify property and lifetime predictions and uncertainties, in response to concerns that aging during long-term stockpile storage may change the microstructure and properties of U-6 wt%Nb alloy components in ways adversely affecting performance. U-6Nb has many desirable properties, but is a complex material because of its gross compositional inhomogeneity (its chemical banding spans 4-8 wt%), its metastable starting microstructure, and the fact that a variety of external factors such as temperature, stress, and gaseous species can cause aging through multiple mechanisms. The most significant aging mechanism identified in earlier studies [2007hac2] is age hardening, phenomenologically defined as increasing hardness and strength and decreasing ductility observed as a function of increasing aging time-at-temperature. The scientific fundamentals of age hardening at temperatures relevant to U-6Nb material processing ({le}200 C) and stockpile storage ({le}60 C) remain unresolved in spite of significant experimental efforts [2007hac2, 2009cla]. Equally problematic is the lack of a well-established U-6Nb component failure criterion. These limitations make the most desirable approach of property response and lifetime prediction - that based on fundamental physics - unattainable at the present time. Therefore, a semi-empirical approach was taken to model the phenomenological property evolution during aging. This enabled lifetime estimates to be made from an assumed failure criterion (derived from a manufacturing acceptance criterion) couched in terms of an age-sensitive property, namely quasi-static tensile elongation to failure. The predictions of this and other age-sensitive properties are also useful for U-6Nb component surveillance studies. Drawing upon a large body of artificial aging data obtained from nonbanded (chemically homogeneous) U-5.6Nb and U-7.7Nb material [2007hacJ ] over 100

  17. Are invertebrates relevant models in ageing research? Focus on the effects of rapamycin on TOR.

    Science.gov (United States)

    Erdogan, Cihan Suleyman; Hansen, Benni Winding; Vang, Ole

    2016-01-01

    Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan prolongation.

  18. Modeled tephra ages from lake sediments, base of Redoubt Volcano, Alaska

    Energy Technology Data Exchange (ETDEWEB)

    Schiff, C J; Kaufman, D S; Wallace, K L; Werner, A; Ku, T L; Brown, T A

    2007-02-25

    A 5.6-m-long lake sediment core from Bear Lake, Alaska, located 22 km southeast of Redoubt Volcano, contains 67 tephra layers deposited over the last 8750 cal yr, comprising 15% of the total thickness of recovered sediment. Using 12 AMS {sup 14}C ages, along with the {sup 137}Cs and {sup 210}Pb activities of recent sediment, we evaluated different models to determine the age-depth relation of sediment, and to determine the age of each tephra deposit. The age model is based on a cubic smooth spline function that was passed through the adjusted tephra-free depth of each dated layer. The estimated age uncertainty of the 67 tephras averages {+-} 105 yr (1{sigma}). Tephra-fall frequency at Bear Lake was among the highest during the past 500 yr, with eight tephras deposited compared to an average of 3.7 per 500 yr over the last 8500 yr. Other periods of increased tephra fall occurred 2500-3500, 4500-5000, and 7000-7500 cal yr. Our record suggests that Bear Lake experienced extended periods (1000-2000 yr) of increased tephra fall separated by shorter periods (500-1000 yr) of apparent quiescence. The Bear Lake sediment core affords the most comprehensive tephrochronology from the base of the Redoubt Volcano to date, with an average tephra-fall frequency of once every 130 yr.

  19. Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria

    Science.gov (United States)

    Goss, James R.; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D.; Glorioso, Joseph C.; Niedernhofer, Laura J.

    2011-01-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1−/Δ mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1−/Δ mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. PMID:21596054

  20. Age differences in the Actiotope Model of Giftedness in a Turkish sample

    Directory of Open Access Journals (Sweden)

    Marilena Z. Leana-Taşcılar

    2015-03-01

    Full Text Available According to the Actiotope Model of Giftedness, person-environment interactions are the core of excellence. Therefore, it is important to evaluate the resources that support the achievement of goals and to provide more efficient resources. These resources are named educational (localized in the environment and learning (localized in the individual capitals. The Questionnaire of Educational and Learning Capital (QELC was developed based on the Actiotope Model of Giftedness and these capitals. The aim of this study is to present gender and age differences in relation to educational and learning capitals, in a Turkish sample of 1,620 students at three different grade levels: fourth graders (231 girls, 239 boys; mean age = 10.15, SD = 0.40, seventh graders (353 girls, 376 boys; mean age = 13.08, SD = 0.34, and 10th graders (274 girls, 147 boys; mean age = 16.20, SD = 0.54. Results of the confirmatory factor analysis showed the expected two-factor structure (educational and learning capitals of the original German version of QELC. The Cronbach's alpha result for the Turkish version of the QELC was .97. The findings suggest that gender differences are more important in the seventh grade (first year of adolescence in favor of girls in economic, cultural, social, organismic, and telic capitals. Results about age differences showed that the younger the students are, the more their achievement is positively affected by the capitals.

  1. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    2013-11-01

    Full Text Available A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  2. Development of the Thai healthy aging model: A grounded theory study.

    Science.gov (United States)

    Thiamwong, Ladda; McManus, Michael S; Suwanno, Jom

    2013-06-01

    To develop a model of healthy aging from the perspective of Thais, a grounded theory approach, including in-depth interviews and focus groups, was used. A purposive sample of 39 community-dwelling adults aged 40-85 years old was interviewed. The Thai healthy aging model composed of three themes: normality, nature, and dharma. In Thai, they are called tham-ma-da, tham-ma-chat, and tham-ma, or "Thai 3Ts". The theme of normality encompasses subthemes of staying physically active by being involved in plenty of physical activities, and being mentally active with creative and thoughtful hobbies and work. The theme of nature encompasses subthemes of living simply and being careful with money. The theme of dharma encompasses subthemes of enjoyment through helping family and participating in community activities, staying away from stress and worries by talking openly and honestly with someone, making merit, and helping other people without expecting anything in return. A greater understanding of healthy aging is a benefit for older adults and healthcare providers in an intervention-design process. Research can contribute valuable information to shape policy for healthy aging as well.

  3. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  4. A comparative study of CART and PTM for modelling water age

    Science.gov (United States)

    Wang, Haiyan; Guo, Xinyu; Liu, Zhe; Gao, Huiwang

    2015-02-01

    CART (Constituent-oriented age and residence time theory) and PTM (Particle-tracking method) are two widely used numerical methods to calculate water age. These two methods are essentially equivalent in theory but their results may be different in practice. The difference of the two methods was evaluated by applying them to calculate water age in an idealized one-dimensional domain. The model results by the two methods are consistent with each other in the case with either spatially uniform flow field or spatially uniform diffusion coefficient. If we allow the spatial variation in horizontal diffusion, a term called pseudo displacement arising from the spatial variation of diffusion coefficient likely plays an important role for the PTM to obtain accurate water age. In particular, if the water particle is released at a place where the diffusion is not the weakest, the water age calculated by the PTM without pseudo displacement is much larger than that by the CART. This suggests that the pseudo displacement cannot be neglected in the PTM to calculate water age in a realistic ocean. As an example, we present its potential importance in the Bohai Sea where the diffusion coefficient varies spatially and greatly.

  5. A Comparative Study of CART and PTM for Modelling Water Age

    Institute of Scientific and Technical Information of China (English)

    WANG Haiyan; GUO Xinyu; LIU Zhe; GAO Huiwang

    2015-01-01

    CART (Constituent-oriented age and residence time theory) and PTM (Particle-tracking method) are two widely used numerical methods to calculate water age. These two methods are essentially equivalent in theory but their results may be different in practice. The difference of the two methods was evaluated by applying them to calculate water age in an idealized one-dimensional domain. The model results by the two methods are consistent with each other in the case with either spatially uniform flow field or spatially uniform diffusion coefficient. If we allow the spatial variation in horizontal diffusion, a term called pseudo displacement arising from the spatial variation of diffusion coefficient likely plays an important role for the PTM to obtain accurate water age. In particular, if the water particle is released at a place where the diffusion is not the weakest, the water age calculated by the PTM without pseudo displacement is much larger than that by the CART. This suggests that the pseudo displacement cannot be neglected in the PTM to calculate water age in a realistic ocean. As an example, we present its potential importance in the Bohai Sea where the diffusion coefficient varies spatially and greatly.

  6. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

    Directory of Open Access Journals (Sweden)

    Shengchang Zhang

    Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

  7. Economic implications of Japan's aging population: a macro-economic demographic modeling approach.

    Science.gov (United States)

    Ogawa, N

    1982-01-01

    This paper utilizes a macroeconomic demographic model to analyze the probable impact of population aging on various public programs in Japan. Rapid fertility decline aided by mortality decline has caused the proportion of the Japanese population aged 65 and over to increase from 4.9% in 1950 to 9.0% in 1980. A population projection based on the 1975 population census assumes a recovery of fertility from a total fertility rate (TFR) of 1.9 in 1976 to 2.16 in 1980 and a gradual decline to 2.1 by 1987, while an alternative projection assumes a continuing fertility decline to a TFR of 1.65 in 2025. According to these assumptions, in 2025 18.12% to 21.29% of the total population would be aged 65 or over and 38.66% to 43.80% of the working age population would be aged 45-64. A macroeconomic neoclassical growth model with some Keynesian features was formulated to evaluate the future impact of population aging on social security programs. Population changes are transmitted to economic variables in the model through the supply of labor, level of savings, public health care plans, and old-age pension schemes. The simulation experiments included the 2 population projections and 2 alternative production functions, 1 with the quality of labor incorporated and 1 without. The results indicated that, regardless of the population projection and production function used, the growth of the economy is likely to slow to 1 or 0% in the beginning of the next century due to decreased growth of the labor force and a change in its quality due to age-compositional variations. Public health insurance schemes and pension plans will require increasing financial resources as a result of accelerated population aging; depending on the choice of benefit levels, the proportion of national income allocated to them is expected to range from 14%-40% in the year 2010. Per capita gross national product will continue to grow despite decreased economic growth, but savings might be adversely affected if the

  8. Numerical flow models and their calibration using tracer based ages: Chapter 10

    Science.gov (United States)

    Sanford, W.

    2013-01-01

    Any estimate of ‘age’ of a groundwater sample based on environmental tracers requires some form of geochemical model to interpret the tracer chemistry (chapter 3) and is, therefore, referred to in this chapter as a tracer model age. the tracer model age of a groundwater sample can be useful for obtaining information on the residence time and replenishment rate of an aquifer system, but that type of data is most useful when it can be incorporated with all other information that is known about the groundwater system under study. groundwater fl ow models are constructed of aquifer systems because they are usually the best way of incorporating all of the known information about the system in the context of a mathematical framework that constrains the model to follow the known laws of physics and chemistry as they apply to groundwater flow and transport. It is important that the purpose or objective of the study be identified first before choosing the type and complexity of the model to be constructed, and to make sure such a model is necessary. The purpose of a modelling study is most often to characterize the system within a numerical framework, such that the hydrological responses of the system can be tested under potential stresses that might be imposed given future development scenarios. As this manual discusses dating as it applies to old groundwater, most readers are likely to be interested in studying regional groundwater flow systems and their water resource potential.

  9. Mathematical analysis of an age-structured model for malaria transmission dynamics.

    Science.gov (United States)

    Forouzannia, Farinaz; Gumel, Abba B

    2014-01-01

    A new deterministic model for assessing the role of age-structure on the transmission dynamics of malaria in a community is designed. Rigorous qualitative analysis of the model reveals that it undergoes the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model co-exists with a stable endemic equilibrium when the associated reproduction number (denoted by R0) is less than unity. It is shown that the backward bifurcation phenomenon is caused by the malaria-induced mortality in humans. A special case of the model is shown to have a unique endemic equilibrium whenever the associated reproduction threshold exceeds unity. Further analyses reveal that adding age-structure to a basic model for malaria transmission in a community does not alter the qualitative dynamics of the basic model, with respect to the existence and asymptotic stability of the associated equilibria and the backward bifurcation property of the model. Numerical simulations of the model show that the cumulative number of new cases of infection and malaria-induced mortality increase with increasing average lifespan and birth rate of mosquitoes.

  10. Resveratrol and the pharmacology of aging: a new vertebrate model to validate an old molecule.

    Science.gov (United States)

    Valenzano, Dario Riccardo; Cellerino, Alessandro

    2006-05-01

    The natural phytoalexin resveratrol, found in grapes and red wine, recently rose to public fame for its positive effects on longevity in yeasts, worms and flies. Resveratrol anti-cancer and anti-inflammatory in vitro action on mammalian cell cultures also suggest a possible positive effect on human health and life-expectancy. To study the effects of resveratrol on vertebrate aging is obviously a particularly relevant question. We have studied resveratrol effects in a very short-lived vertebrate: the annual fish Nothobranchius furzeri. Resveratrol treatment prolonged lifespan and delayed the onset of age-related dysfunctions in this fish. This result identifies resveratrol as the first molecule which consistently retards aging in organisms as diverse as yeast, worm, fly and fish, but it also reveals the potential of this short-lived fish as an animal model for pharmacological research. Moreover, being related to stickleback (Gasterosteus aculeatus) the "pufferfishes" Takifugu and Tetraodon, and even more closely related to medaka (Oryzias latipes), it can greatly beneficiate from the recent development of genomic resources for these fish models and in the future become a complete model system for the aging research community.

  11. Testing the Neoclassical Migration Model: Overall and Age-Group Specific Results for German Regions

    DEFF Research Database (Denmark)

    Mitze, Timo; Reinkowski, Janina

    This paper tests the empirical validity of the neoclassical migration model in predicting German internal migration flows. We estimate static and dynamic migration functions for 97 Spatial Planning Regions between 1996 and 2006 using key labor market signals including income and unemployment...... as for age-group specific estimates. Thereby, the impact of labor market signals is tested to be of greatest magnitude for workforce relevant age-groups and especially young cohorts between 18 to 25 and 25 to 30 years. This latter result underlines the prominent role played by labor market conditions...

  12. Optimal control of an influenza model with seasonal forcing and age-dependent transmission rates.

    Science.gov (United States)

    Lee, Jeehyun; Kim, Jungeun; Kwon, Hee-Dae

    2013-01-21

    This study considers an optimal intervention strategy for influenza outbreaks. Variations in the SEIAR model are considered to include seasonal forcing and age structure, and control strategies include vaccination, antiviral treatment, and social distancing such as school closures. We formulate an optimal control problem by minimizing the incidence of influenza outbreaks while considering intervention costs. We examine the effects of delays in vaccine production, seasonal forcing, and age-dependent transmission rates on the optimal control and suggest some optimal strategies through numerical simulations.

  13. Positive mutations and mutation-dependent Verhulst factor in Penna ageing model

    Science.gov (United States)

    Moss de Oliveira, S.; Stauffer, D.; de Oliveira, P. M. C.; Sá Martins, J. S.

    2004-02-01

    We modify twice the Penna model for biological ageing. First, we introduce back (good) mutations and a memory for them into the model. It allows us to observe an improvement of the species fitness over long-time scales as well as punctuated equilibrium. Second, we adopt a food/space competition factor that depends on the number of accumulated mutations in the individuals genomes, and get rid of the fixed limiting number of allowed mutations. Besides reproducing the main results of the standard model, we also observe a mortality maximum for the oldest old.

  14. Influence of Fuzzy Parameters on the Modeling Quality of XLPE Insulation Properties under Thermal Aging

    Directory of Open Access Journals (Sweden)

    Lakhdar Bessissa

    2016-03-01

    Full Text Available In this work, we have used the fuzzy logic approach to predict mechanical properties (hot set test of cross-linked polyethylene (XLPE used as insulation in high voltage cables. The studied property presents non linear variations according to the aging time under high temperatures. So it is very difficult to find a theoretical or experimental model of the properties evolution under thermal aging. For that reason, several factors have been considered such as aging time and applied temperature. The obtained results are very encouraging and pointed out that the fuzzy logic is a powerful tool to predict the insulation proprieties. In other words, the obtained results are in good accordance with the experimental results with an acceptable error margin.

  15. Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models.

    Science.gov (United States)

    He, Liang; Sillanpää, Mikko J; Silventoinen, Karri; Kaprio, Jaakko; Pitkäniemi, Janne

    2016-04-01

    Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene-environment (G×E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametricG×Einteraction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more

  16. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  17. In vitro model adapted to the study of skin ageing induced by air pollution.

    Science.gov (United States)

    Lecas, Sarah; Boursier, Elsa; Fitoussi, Richard; Vié, Katell; Momas, Isabelle; Seta, Nathalie; Achard, Sophie

    2016-09-30

    More than a barrier against environmental agents, skin reflects individual health and is a visible sign of ageing with the progressive loss of skin integrity. In order to evaluate the consequences of an environmental complex mixture, with tobacco smoke (TS) as model, on cellular and morphological changes, a 3D skin model was used. Morphologically, tissue integrity was intact after one TS-exposure while the superficial layers were drastically reduced after two TS-exposures. However, TS modified epidermal organisation at the molecular level after just one exposure. A decrease in loricrin protein staining was showed in the epidermis, while production of inflammatory cytokines (IL-8, IL-1α, IL-18) and metalloproteinase (MMP-1, MMP-3) were stimulated. Oxidative stress was also illustrated with an increase in 4-HNE protein staining. Moreover, terminal differentiation, cell-cell junction and anchorage gene expression was down-regulated in our model after one TS-exposure. In conclusion, tobacco smoke impacted the fundamental functions of skin, namely tissue anchorage, cornification and skin desquamation. Oxidative stress resulted in skin ageing. The tissue was even reactive with the inflammatory pathways, after one TS-exposure. The 3D-RHE model is appropriate for evaluating the impact of environmental pollutants on skin ageing.

  18. Forest carbon uptake in North America's aging temperate deciduous forests: A data-theory-model mismatch?

    Science.gov (United States)

    Gough, C. M.; Curtis, P.; Bond-Lamberty, B. P.; Hardiman, B. S.; Scheuermann, C. M.; Nave, L. E.; Nadelhoffer, K. J.

    2015-12-01

    Century-old temperate deciduous forests in the US upper Midwest and Northeast power much of North America's terrestrial carbon sink, but these forests' carbon uptake capacity is expected to soon decline. But will this really happen? We marshal empirical data and ecological theory to show that declines in carbon uptake are not imminent in regrown temperate deciduous forests during coming decades, despite long-held assumptions and modeling results that predict declining carbon uptake during middle stages of ecosystem development. Age and production data for temperate deciduous forests, synthesized from published literature, do not provide evidence for declining net primary and ecosystem production (NPP and NEP, respectively) within the age-range most regional forests will occupy over the next half-century. Ecological theory suggests a mechanism for sustained carbon uptake in the region's aging forests in which high-frequency, low-severity disturbances maintain NPP and NEP by increasing ecosystem complexity. This theoretical model is supported by observations from the Forest Accelerated Succession Experiment in Michigan, USA, but such mechanisms sustaining production in old forests are not broadly represented in ecosystem models. Ecosystems experiencing low-frequency, high-severity disturbances that simplify ecosystem complexity do exhibit declining production during middle stages of succession, but we suggest that such scenarios have exerted a disproportionate influence on prevailing modeling and ecological assumptions regarding age-related declines in forest production. We conclude that there is wide ecological space for forests to sustain high rates of carbon uptake during middle stages of ecosystem development, and that advancing mechanistic understanding of long-term forest carbon cycle dynamics is essential to modeling the continent's future carbon sink strength.

  19. Patterns of lung cancer mortality in 23 countries: Application of the Age-Period-Cohort model

    Directory of Open Access Journals (Sweden)

    Huang Yi-Chia

    2005-03-01

    Full Text Available Abstract Background Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. Methods International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC model was used to estimate the period effect (adjusted for age and cohort effects for mortality from lung cancer. Results The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. Conclusion Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries.

  20. A computational model of inferior colliculus responses to amplitude modulated sounds in young and aged rats

    Directory of Open Access Journals (Sweden)

    Cal Francis Rabang

    2012-11-01

    Full Text Available The inferior colliculus (IC receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated (AM tone or noise carriers at 20-40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function (rMTF tuning shape. Their temporal modulation transfer functions (tMTFs were also measured. These spike patterns provided experimental measures of rate, vector strength and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response subtypes were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with

  1. Influence of age and sex on pharmacodynamics of propofol in neurosurgical patients: model development

    Institute of Scientific and Technical Information of China (English)

    Yu-hong LI; Fu-sheng WU; Jian-guo XU

    2006-01-01

    Aim: To determine propofol concentration in the cerebral spinal fluid (CSF) of neurosurgical patients and carry out a preliminary population pharmacodynamic study. Methods: Twenty-seven elective neurosurgical patients (12 men and 15 women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 min and an infusion of 10 mg/kg per h for 5 min. Frequent CSF samples were drawn and assayed for propofol concentration. The bispectral index (BIS) was used to measure the drug effect. All data were analyzed first with the Excel software package, then pharmacodynamics modeling was performed using the NONMEM software package. Results: The CSF concentration was related to the drug effect with linear and sigmoid Emax models. The parameters for the linear addictive model were a= 1.11 and b=95.4. The parameters for the linear exponential model were a= 1.05 and b=92.7. The parameters for the sigmoid Emax model were Emax=119, EC50= 53.6 ng/Ml, and W=1.51. When the covariates of age, weight and sex were considered, the parameters of models, objective function, the standard error of the mean and the prediction error were not optimized. Conclusion: Linear additive, linear exponential and sigmoid Emax models can be used to describe the pharmacodynamics of propofol with respect to the concentration in CSF. In this small population, age (17-74 years), weight (47-98 kg) and sex did not influence any of the pharmacodynamic parameters of propofol. To verify these preliminary results, a larger study population is required.

  2. The mitochondrial theory of aging: insight from transgenic and knockout mouse models.

    Science.gov (United States)

    Jang, Youngmok C; Van Remmen, Holly

    2009-04-01

    A substantial body of evidence has accumulated over the past 35 years in support of a role for oxidative damage to the mitochondrial respiratory chain and mitochondrial DNA in the determination of mammalian lifespan. The goal of this review is to provide a concise summary of recent studies using transgenic and knockout mouse models with altered expression of mitochondrial antioxidant enzymes (MnSOD (Sod2Tg and Sod2(+/-)), thioredoxin 2 (Trx2(+/-)), mitochondrial targeted catalase (mCAT) and mutant mice models that have been genetically manipulated to increase mitochondrial deletions or mutations (Polgamma(D257A/D257A) mutant mice) to examine the role of mitochondrial oxidative stress in aging. The majority of studies using these strategies do not support a clear role for mitochondrial oxidative stress or a vicious cycle of oxidative damage in the determination of lifespan in mice and furthermore do not support the free radical theory of aging. However, several key questions remain to be addressed and clearly more studies are required to fully understand the role of mitochondria in age-related disease and aging.

  3. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Marine Joly

    Full Text Available Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD and reversal learning (PDR tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

  4. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus).

    Science.gov (United States)

    Joly, Marine; Ammersdörfer, Sandra; Schmidtke, Daniel; Zimmermann, Elke

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

  5. Cscibox: A Software System for Age-Model Construction and Evaluation

    Science.gov (United States)

    Bradley, E.; Anderson, K. A.; Marchitto, T. M., Jr.; de Vesine, L. R.; White, J. W. C.; Anderson, D. M.

    2014-12-01

    CSciBox is an integrated software system for the construction and evaluation of age models of paleo-environmetal archives, both directly dated and cross dated. The time has come to encourage cross-pollinization between earth science and computer science in dating paleorecords. This project addresses that need. The CSciBox code, which is being developed by a team of computer scientists and geoscientists, is open source and freely available on github. The system employs modern database technology to store paleoclimate proxy data and analysis results in an easily accessible and searchable form. This makes it possible to do analysis on the whole core at once, in an interactive fashion, or to tailor the analysis to a subset of the core without loading the entire data file. CSciBox provides a number of 'components' that perform the common steps in age-model construction and evaluation: calibrations, reservoir-age correction, interpolations, statistics, and so on. The user employs these components via a graphical user interface (GUI) to go from raw data to finished age model in a single tool: e.g., an IntCal09 calibration of 14C data from a marine sediment core, followed by a piecewise-linear interpolation. CSciBox's GUI supports plotting of any measurement in the core against any other measurement, or against any of the variables in the calculation of the age model-with or without explicit error representations. Using the GUI, CSciBox's user can import a new calibration curve or other background data set and define a new module that employs that information. Users can also incorporate other software (e.g., Calib, BACON) as 'plug ins.' In the case of truly large data or significant computational effort, CSciBox is parallelizable across modern multicore processors, or clusters, or even the cloud. The next generation of the CSciBox code, currently in the testing stages, includes an automated reasoning engine that supports a more-thorough exploration of plausible age models

  6. Age- and bite-structured models for vector-borne diseases

    Directory of Open Access Journals (Sweden)

    K.S. Rock

    2015-09-01

    Full Text Available The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host–vector model, whereas other controls including treatment of humans may be more effective than previously thought.

  7. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  8. Parameter sensitivity analysis of a simplified electrochemical and thermal model for Li-ion batteries aging

    Science.gov (United States)

    Edouard, C.; Petit, M.; Forgez, C.; Bernard, J.; Revel, R.

    2016-09-01

    In this work, a simplified electrochemical and thermal model that can predict both physicochemical and aging behavior of Li-ion batteries is studied. A sensitivity analysis of all its physical parameters is performed in order to find out their influence on the model output based on simulations under various conditions. The results gave hints on whether a parameter needs particular attention when measured or identified and on the conditions (e.g. temperature, discharge rate) under which it is the most sensitive. A specific simulation profile is designed for parameters involved in aging equations in order to determine their sensitivity. Finally, a step-wise method is followed to limit the influence of parameter values when identifying some of them, according to their relative sensitivity from the study. This sensitivity analysis and the subsequent step-wise identification method show very good results, such as a better fitting of the simulated cell voltage with experimental data.

  9. Exposure age and ice-sheet model constraints on Pliocene East Antarctic ice sheet dynamics.

    Science.gov (United States)

    Yamane, Masako; Yokoyama, Yusuke; Abe-Ouchi, Ayako; Obrochta, Stephen; Saito, Fuyuki; Moriwaki, Kiichi; Matsuzaki, Hiroyuki

    2015-04-24

    The Late Pliocene epoch is a potential analogue for future climate in a warming world. Here we reconstruct Plio-Pleistocene East Antarctic Ice Sheet (EAIS) variability using cosmogenic nuclide exposure ages and model simulations to better understand ice sheet behaviour under such warm conditions. New and previously published exposure ages indicate interior-thickening during the Pliocene. An ice sheet model with mid-Pliocene boundary conditions also results in interior thickening and suggests that both the Wilkes Subglacial and Aurora Basins largely melted, offsetting increased ice volume. Considering contributions from West Antarctica and Greenland, this is consistent with the most recent IPCC AR5 estimate, which indicates that the Pliocene sea level likely did not exceed +20 m on Milankovitch timescales. The inception of colder climate since ∼3 Myr has increased the sea ice cover and inhibited active moisture transport to Antarctica, resulting in reduced ice sheet thickness, at least in coastal areas.

  10. Comparative modeling of Bronze Age land use in the Malatya Plain (Turkey)

    Science.gov (United States)

    Arıkan, Bülent; Restelli, Francesca Balossi; Masi, Alessia

    2016-03-01

    Computational modeling in archeology has proven to be a useful tool in quantifying changes in the paleoenvironment. This especially useful method combines data from diverse disciplines to answer questions focusing on the complex and non-linear aspects of human-environment interactions. The research presented here uses various proxy records to compare the changes in climate during the Bronze Age in the Malatya Plain in eastern Anatolia, which is situated at the northern extremity of northern Mesopotamia. Extensive agropastoral land use modeling was applied to three sites of different size and function in the Malatya Plain during the Early Bronze Age I period to simulate the varying scale and intensity of human impacts in relation to changes in the level of social organization, demography, and temporal length. The results suggest that even in land use types subjected to a light footprint, the scale and intensity of anthropogenic impacts change significantly in relation to the level of social organization.

  11. Social Dancing for Successful Ageing: Models for Health, Happiness and Social Inclusion amongst Senior Citizens

    Directory of Open Access Journals (Sweden)

    Jonathan Skinner

    2013-03-01

    Full Text Available Abstract: This article presents findings from a qualitative study of social dancing for successful ageing amongst senior citizens in three locales: in Blackpool (GB, around Belfast (NI, and in Sacramento (US. Findings also attest to the social, psychological and health benefits of social dancing amongst senior citizens. They also articulate three different social dancing models: social dance as tea dance (Sacramento, social dance as practice dance (Blackpool, social dance as motility (Belfast and environs.

  12. A new age model for the early-middle Miocene in the North Alpine Foreland Basin

    Science.gov (United States)

    Reichenbacher, Bettina; Krijgsman, Wout; Pippèrr, Martina; Sant, Karin; Kirscher, Uwe

    2016-04-01

    The establishment of high-resolution age models for sedimentary successions is crucial for numerous research questions in the geosciences and related disciplines. Such models provide an absolute chronology that permits precise dating of depositional episodes and related processes such as mountain uplift or climate change. Recently, our work in the Miocene sediments of the North Alpine Foreland Basin (NAFB) has revealed a significantly younger age (16.6 Myr) for sediments that were thought to have been deposited 18 Myr ago. This implies that a fundamentally revised new age model is needed for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB (20 to 15-Myr). Our new data also indicate that previously published reconstructions of early-middle Miocene palaeogeography, sedimentation dynamics, mountain uplift and climate change in the NAFB all require a critical review and revision. Further, the time-span addressed is of special interest, since it encompasses the onset of a global warming phase. However, it appears that a fundamentally revised new age model for the entire suite of lower-middle Miocene sedimentary rocks in the NAFB can only be achieved based on a 500 m deep drilling in the NAFB for which we currently seek collaboration partners to develop a grant application to the International Continental Deep Drilling Program (ICDP). Reference: Reichenbacher, B., W. Krijgsman, Y. Lataster, M. Pippèrr, C. G. C. Van Baak, L. Chang, D. Kälin, J. Jost, G. Doppler, D. Jung, J. Prieto, H. Abdul Aziz, M. Böhme, J. Garnish, U. Kirscher, and V. Bachtadse. 2013. A new magnetostratigraphic framework for the Lower Miocene (Burdigalian/Ottnangian, Karpatian) in the North Alpine Foreland Basin. Swiss Journal of Geosciences 106:309-334.

  13. A multi-region nonlinear age-size structured fish population model

    CERN Document Server

    Faugeras, Blaise

    2010-01-01

    The goal of this paper is to present a generic multi-region nonlinear age-size structured fish population model, and to assess its mathematical well-posedness. An initial-boundary-value problem is formulated. Existence and uniqueness of a positive weak solution is proved. Eventually, a comparison result is derived: the population of all regions decreases as the mortality rate increases in at least one region.

  14. Mathematical model of mean age, mean arsenic dietary dose and age-specific prevalence rate from endemic chronic arsenic poisoning: a human toxicology study

    Energy Technology Data Exchange (ETDEWEB)

    Zald' ivar, R.; Ghai, G.L.

    1980-01-01

    The aim of this investigation was to develop a mathematical model of mean age, mean arsenic dietary dose, and age-specific prevalence rate for endemic chronic arsenic poisoning. Data on mean age (years), mean arsenic dietary dose (mg/kg body weight/day), and age-specific prevalence rate per 100,000 population for endemic chronic arsenic poisoning in Antofagasta Commune, northern Chile, for the 1968 to 1971 period, were collected. Endemic chronic arsenic poisoning means here chronic arsenical dermatosis associated with marked or sever symptoms (or signs) of chronic arsenic poisoning (chronic diarrhea, hepatic cirrohsis, chronic bronchitis, bronchiectasis, recurrent broncho-pneumonia, cardiomegaly, systemic occlusive arterial disease, cerebral thrombosis, etc.). There was a strong positive correlation between age-specific pevalence rate per 100,000 population and mean arsenic dose (r = + 0.9593) and a negative correlation between prevalence rate and mean age (r = 0.8789). These findings show that the prevalence rate declines with the advancing age and increases with the increase of arsenic dose. A multiple linear regression model E(y) = alpha + beta X1 + gamma X2, where y represents the age-specific prevalence rate per 100,000 population, X1 the mean arsenic dose, and X2 the mean age, was fitted to the data. The estimates of the parameters (alpha, beta, and gamma) were obtained by minimizing the residual sum of squares sigma(y - alpha - beta X1 - gamma X2)2. The following multiple linear regression equation was obtained: Y = 202.161 + 8452.455 X1 - 2.394 X2. Of the total variability in the prevalence rate, 96.22 percent was accounted for by the multiple regression.

  15. Structural equation modeling identifies markers of damage and function in the aging male Fischer 344 rat.

    Science.gov (United States)

    Grunz-Borgmann, Elizabeth A; Nichols, LaNita A; Wiedmeyer, Charles E; Spagnoli, Sean; Trzeciakowski, Jerome P; Parrish, Alan R

    2016-06-01

    The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, elevations in the more sensitive markers of function, plasma cystatin C and proteinuria, were detectable at 16 and 18 months, respectively. Interestingly, cystatin C levels were not corrected by caloric restriction. Urinary Kim-1, a marker of CKD, was elevated as early as 16 months. Klotho gene expression was significantly decreased at 24 months, but not at earlier timepoints. Alterations in renal structure, glomerulosclerosis and tubulointerstitial fibrosis, were noted at 16 months, with little change from 18 to 24 months. Tubulointerstitial inflammation was increased at 16 months, and remained similar from 18 to 24 months. A SEM (structural equation modeling) model of age-related renal dysfunction suggests that proteinuria is a marker of renal damage, while urinary Kim-1 is a marker of both damage and function. Taken together, these results demonstrate that age-dependent nephropathy begins as early as 16 months and progresses rapidly over the next 8 months.

  16. Prediction of residual stress due to early age behaviour of massive concrete structures: on site experiments and macroscopic modelling

    CERN Document Server

    Zreiki, Jihad; Chaouche, Mohend; Moranville, Micheline

    2008-01-01

    Early age behaviour of concrete is based on complex multi-physical and multiscale phenomena. The predication of both cracking risk and residual stresses in hardened concrete structures is still a challenging task. We propose in this paper a practical method to characterize in the construction site the material parameters and to identify a macroscopic model from simple tests. We propose for instance to use a restrained shrinkage ring test to identify a basic early age creep model based on a simple ageing visco-elastic Kelvin model. The strain data obtained from this test can be treated through an early age finite element incremental procedure such that the fitting parameters of the creep law can be quickly identified. The others properties of concrete have been measured at different ages (elastic properties, hydration kinetics, and coefficient of thermal expansion). From the identified early age model, we computed the temperature rise and the stress development in a non reinforced concrete stress for nuclear w...

  17. Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging.

    Science.gov (United States)

    Ghanbari, Samane; Yonessi, Mahsa; Mohammadirad, Azadeh; Gholami, Mahdi; Baeeri, Maryam; Khorram-Khorshid, Hamid Reza; Gharibdoost, Farhad; Abdollahi, Mohammad

    2012-10-27

    The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

  18. Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging

    Directory of Open Access Journals (Sweden)

    Ghanbari Samane

    2012-10-01

    Full Text Available Abstract The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kg administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks; IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks, Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks; and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α, interlukine-1β (IL-β, interlukine-6 (IL-6, Nuclear Factor-kappaB (NF-κb, total antioxidant power (TAP, lipid peroxides (LPO and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S were measured in the blood. Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

  19. Effects of IMOD and Angipars on Mouse D-Galactose-Induced Model of Aging

    Directory of Open Access Journals (Sweden)

    Samane Ghanbari

    2012-10-01

    Full Text Available The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kgadministered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day]intraperitoneally for 4 weeks; IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks, Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks; and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α, interlukine-1β (IL-β, interlukine-6 (IL-6, NF-kappaB (NF-κb, total antioxidant power (TAP, lipid peroxides (LPO and male sex hormones i.e.testosterone and dehydroepiandrosterone-sulfate (DHEA-S were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones that were declined in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

  20. Aging into perceptual control: A Dynamic Causal Modeling for fMRI study of bistable perception

    Directory of Open Access Journals (Sweden)

    Ehsan eDowlati

    2016-03-01

    Full Text Available Aging is accompanied by stereotyped changes in functional brain activations, for example a cortical shift in activity patterns from posterior to anterior regions is one hallmark revealed by functional magnetic resonance imaging (fMRI of aging cognition. Whether these neuronal effects of aging could potentially contribute to an amelioration of or resistance to the cognitive symptoms associated with psychopathology remains to be explored. We used a visual illusion paradigm to address whether aging affects the cortical control of perceptual beliefs and biases. Our aim was to understand the effective connectivity associated with volitional control of ambiguous visual stimuli and to test whether greater top-down control of early visual networks emerged with advancing age. Using a bias training paradigm for ambiguous images we found that older participants (n = 16 resisted experimenter-induced visual bias compared to a younger cohort (n = 14 and that this resistance was associated with greater activity in prefrontal and temporal cortices. By applying Dynamic Causal Models for fMRI we uncovered a selective recruitment of top-down connections from the middle temporal to lingual gyrus by the older cohort during the perceptual switch decision following bias training. In contrast, our younger cohort did not exhibit any consistent connectivity effects but instead showed a loss of driving inputs to orbitofrontal sources following training. These findings suggest that perceptual beliefs are more readily controlled by top-down strategies in older adults and introduce age-dependent neural mechanisms that may be important for understanding aberrant belief states associated with psychopathology.

  1. Preparing the Workforce for Healthy Aging Programs: The Skills for Healthy Aging Resources and Programs (SHARP) Model

    Science.gov (United States)

    Frank, Janet C.; Altpeter, Mary; Damron-Rodriguez, JoAnn; Driggers, Joann; Lachenmayr, Susan; Manning, Colleen; Martinez, Dana M.; Price, Rachel M.; Robinson, Patricia

    2014-01-01

    Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop…

  2. Modelling the behavior of the Jakobshavn glacier since the end of the Little Ice Age

    DEFF Research Database (Denmark)

    Muresan, Ioana Stefania; Khroulev, Constantine; Khan, Shfaqat Abbas;

    2014-01-01

    Current model estimates of the Greenland Ice Sheet (GrIS) are almost entirely based on coarse grids (>10km) and constrained by climate models that span from 60s to present. To improve the projection of future sea level rise, a long-term data record that reveals the mass balance beyond decadal...... timescale is required. Here, we use a continuous 171 year reconstruction (since the end of the Little Ice Age) by J.E. Box of the Greenland Ice Sheet climatic surface mass balance and its sub-components to study the interaction between climate and the cryosphere originating in changes in the surface mass...... balance and dynamics of the GrIS over the last 171 years. Throughout our study, we use the Parallel Ice Sheet Model (PISM) capabilities. The initialization of the ice sheet is performed on a 5 km grid using paleo climatic forcing (-125 ka to present) based on a positive degree day (PDD) model...

  3. Modeling short wave solar radiation using the JGrass-NewAge System

    Directory of Open Access Journals (Sweden)

    G. Formetta

    2012-12-01

    Full Text Available This paper presents two new modelling components based on the Object Modelling System v3 for the calculation of the shortwave incident radiation (R^sw↓ on complex topography settings, and the implementation of several ancillary tools. The first component, NewAGE-SwRB, accounts for slope, aspect, shadow and the topographical information of the sites, and use suitable parametrisation for obtaining the cloudless irradiance. A second component, NewAGE-DEC-MOD's is implemented to estimate the irradiance reduction due to the presence of clouds, according to three parameterisations. To obtain a working modelling composition, suitable to be compared with ground data at measurement stations, the two components are connected to a Kriging component, and, with the use of a further component NewAGE-V (verification package, the performance of modeled (R^sw↓ is quantitatively evaluated. The two components (and the various parametrisations they contain are tested using the data from three basins catchments, and some simple verification test is made to assess the goodness of the methods used. The components are part of a larger system, JGrass-NewAGE, their input and outputs are given as geometrical objects immediately visualisable in a GIS (for instance the companion uDig, and can be used seamlessly with the various modelling solutions available in JGrass-NewAGE for the estimation of long wave radiation, evapotranspiration, and snow melting, as well as stand-alone components to just estimate shortwave radiation for various uses. The modularity of the approach is shown to be extensible to more accurate physical-statistical studies aimed to assess in deep the components performances and extends spatially their results, without the necessity of recoding any part of the component but just

  4. A ternary age-mixing model to explain contaminant occurrence in a deep supply well.

    Science.gov (United States)

    Jurgens, Bryant C; Bexfield, Laura M; Eberts, Sandra M

    2014-09-01

    The age distribution of water from a public-supply well in a deep alluvial aquifer was estimated and used to help explain arsenic variability in the water. The age distribution was computed using a ternary mixing model that combines three lumped parameter models of advection-dispersion transport of environmental tracers, which represent relatively recent recharge (post-1950s) containing volatile organic compounds (VOCs), old intermediate depth groundwater (about 6500 years) that was free of drinking-water contaminants, and very old, deep groundwater (more than 21,000 years) containing arsenic above the USEPA maximum contaminant level of 10 µg/L. The ternary mixing model was calibrated to tritium, chloroflorocarbon-113, and carbon-14 (14C) concentrations that were measured in water samples collected on multiple occasions. Variability in atmospheric 14C over the past 50,000 years was accounted for in the interpretation of (14) C as a tracer. Calibrated ternary models indicate the fraction of deep, very old groundwater entering the well varies substantially throughout the year and was highest following long periods of nonoperation or infrequent operation, which occured during the winter season when water demand was low. The fraction of young water entering the well was about 11% during the summer when pumping peaked to meet water demand and about 3% to 6% during the winter months. This paper demonstrates how collection of multiple tracers can be used in combination with simplified models of fluid flow to estimate the age distribution and thus fraction of contaminated groundwater reaching a supply well under different pumping conditions.

  5. Mechanical Characterization and Constitutive Modeling of Human Trachea: Age and Gender Dependency

    Directory of Open Access Journals (Sweden)

    Farzaneh Safshekan

    2016-06-01

    Full Text Available Tracheal disorders can usually reduce the free lumen diameter or wall stiffness, and hence limit airflow. Trachea tissue engineering seems a promising treatment for such disorders. The required mechanical compatibility of the prepared scaffold with native trachea necessitates investigation of the mechanical behavior of the human trachea. This study aimed at mechanical characterization of human tracheas and comparing the results based on age and gender. After isolating 30 human tracheas, samples of tracheal cartilage, smooth muscle, and connective tissue were subjected to uniaxial tension to obtain force-displacement curves and calculate stress-stretch data. Among several models, the Yeoh and Mooney-Rivlin hyperelastic functions were best able to describe hyperelastic behavior of all three tracheal components. The mean value of the elastic modulus of human tracheal cartilage was calculated to be 16.92 ± 8.76 MPa. An overall tracheal stiffening with age was observed, with the most considerable difference in the case of cartilage. Consistently, we noticed some histological alterations in cartilage and connective tissue with aging, which may play a role in age-related tracheal stiffening. No considerable effect of gender on the mechanical behavior of tracheal components was observed. The results of this study can be applied in the design and fabrication of trachea tissue engineering scaffolds.

  6. Transit times and age distributions for reservoir models represented as nonlinear non-autonomuous systems

    Science.gov (United States)

    Müller, Markus; Meztler, Holger; Glatt, Anna; Sierra, Carlos

    2016-04-01

    We present theoretical methods to compute dynamic residence and transit time distributions for non-autonomous systems of pools governed by coupled nonlinear differential equations. Although transit time and age distributions have been used to describe reservoir models for a long time, a closer look to their assumptions reveals two major restrictions of generality in previous studies. First, the systems are assumed to be in equilibrium; and second, the equations under consideration are assumed to be linear. While both these assumptions greatly ease the computation and interpretation of transit time and age distributions they are not applicable to a wide range of problems. Moreover, the transfer of previous results learned from linear systems in steady state to the more complex nonlinear non-autonomous systems that do not even need to have equilibria, can be dangerously misleading. Fortunately the topic of time dependent age and transit time distributions has received some attention recently in hydrology, we aim to compute these distributions for systems of multiple reservoirs. We will discuss how storage selection functions can augment the information represented in an ODE system describing a system of reservoirs. We will present analytical and numerical algorithms and a Monte Carlo simulator to compute solutions for system transit time and age distributions for system-wide storage selection functions including the most simple, but important case of well mixed pools.

  7. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model.

    Science.gov (United States)

    Sinha, Indranil; Sinha-Hikim, Amiya P; Wagers, Amy J; Sinha-Hikim, Indrani

    2014-09-01

    As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. The surgical joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factors required for the improvement seen in muscles in old mice in heterochronic parabiosis with young mice. To test this hypothesis, we established the following heterochronic parabioses between young (Y; 5 months old) and old (O; 22-23 months old) C57BL6 male mice: (1) Y:O; (2) castrated Y:O (ØY:O); (3) castrated + testosterone-treated Y:O (ØY + T:O). A group of normal young mice received empty implants, and old mice were used as controls. Parabiotic pairings were maintained for 4 weeks prior to analysis. Serum testosterone levels were three-fold higher in young than in old mice. The ØY + T:O pairing demonstrated significantly elevated levels of serum testosterone and an improvement in gastrocnemius muscle weight, muscle ultrastructure, muscle fiber cross-sectional area, and Notch-1 expression in old mice. These changes were not present in aged mice in the ØY:O pairing. These data indicate that testosterone has a critical role in mediating the improved muscle mass and ultrastructure seen in an experimental model of heterochronic parabiosis.

  8. Asteroid age distributions determined by space weathering and collisional evolution models

    Science.gov (United States)

    Willman, Mark; Jedicke, Robert

    2011-01-01

    We provide evidence of consistency between the dynamical evolution of main belt asteroids and their color evolution due to space weathering. The dynamical age of an asteroid's surface (Bottke, W.F., Durda, D.D., Nesvorný, D., Jedicke, R., Morbidelli, A., Vokrouhlický, D., Levison, H. [2005]. Icarus 175 (1), 111-140; Nesvorný, D., Jedicke, R., Whiteley, R.J., Ivezić, Ž. [2005]. Icarus 173, 132-152) is the time since its last catastrophic disruption event which is a function of the object's diameter. The age of an S-complex asteroid's surface may also be determined from its color using a space weathering model (e.g. Willman, M., Jedicke, R., Moskovitz, N., Nesvorný, D., Vokrouhlický, D., Mothé-Diniz, T. [2010]. Icarus 208, 758-772; Jedicke, R., Nesvorný, D., Whiteley, R.J., Ivezić, Ž., Jurić, M. [2004]. Nature 429, 275-277; Willman, M., Jedicke, R., Nesvorny, D., Moskovitz, N., Ivezić, Ž., Fevig, R. [2008]. Icarus 195, 663-673. We used a sample of 95 S-complex asteroids from SMASS and obtained their absolute magnitudes and u, g, r, i, z filter magnitudes from SDSS. The absolute magnitudes yield a size-derived age distribution. The u, g, r, i, z filter magnitudes lead to the principal component color which yields a color-derived age distribution by inverting our color-age relationship, an enhanced version of the 'dual τ' space weathering model of Willman et al. (2010). We fit the size-age distribution to the enhanced dual τ model and found characteristic weathering and gardening times of τw = 2050 ± 80 Myr and τg=4400-500+700Myr respectively. The fit also suggests an initial principal component color of -0.05 ± 0.01 for fresh asteroid surface with a maximum possible change of the probable color due to weathering of Δ PC = 1.34 ± 0.04. Our predicted color of fresh asteroid surface matches the color of fresh ordinary chondritic surface of PC1 = 0.17 ± 0.39.

  9. Anti-ageing effects of a new Dimethylaminoethanol-based formulation on D-Galactose induced skin ageing model of rat

    Institute of Scientific and Technical Information of China (English)

    YAN Bing-jian; YUAN Feng; ZHAO Cai-ling; LIU Su

    2015-01-01

    Background Dimethylaminoethanol has been widely used to fight against wrinkles, in the field of aesthetic medicine there is an increasing demand for safe and effective Dimethylaminoethanol-based products to counteract the ageing process. Objective To evaluate the anti-ageing effects of a new DMAE-based formulation. Methods 30 male rats were randomly allocated into treatment,D-gal ageing modeland control groups, each of which contained ten rats. Treatment group and D-gal ageing model group were subcutaneously injected with D- galactose prepared in normal saline 125mg·kg-1·d-1 for 42d. Control groups were injected with normal saline for 42 d with same method and dose. From the 18th day,after shaving their hair,the treatment grouprats were injected thisnew DMAE-based formulation at a dose of 1ml per week for 4 weeks in the Dermis of two sides hip skin mark zone.Meanwhile,D-gal ageing model group rats were administrated the same volume of normal saline with same method. Skin specimens were obtained 3days after the last treatment. Dermal collagen density and dermal thickness were evaluated by H&E and Masson-trichrome staining. And mRNA expressions of TGFβ1, Smad3, Type I,Type III Pro-collagen,TIMP-1, MMP-1,were assessed by Real-time quantitative polymerase chain reaction. Results Dermal thickness, dermal collagen density and hydroxyproline content in treatment group increased significantly comparing with D-gal ageing model group. No differences were found in mRNA expression of MMP-1 and Type III Pro-collagen between the treatment group and D-gal ageing model group. In addition, mRNA expression of TGFβ1, Type I Pre-collagen , TIMP1 and smad3 in treatment group were significantly up-regulated in contrast with D-gal ageing model and control group. Conclusion This new DMAE-based formulationcould generate anti-ageing effects by activating collagen synthesisthrough TGF-β1/Smads signaling pathway.

  10. The Grateful Aging Program: A Naturalistic Model of Transformation and Healing into the Second Half of Life

    Science.gov (United States)

    Schlitz, Marilyn

    2017-01-01

    Objectives: Understanding and managing the process of aging is a central issue in modern society. This is a critical factor given the demographic shift toward an aging population and the negative stereotypes around aging that can limit people’s worldview on aging with gratitude and well-being. Methods: Building on three decades of qualitative and quantitative studies on positive worldview transformation at the California-based Institute of Noetic Sciences, this article applies an empirically derived naturalistic model of transformation to aging. The Grateful Aging Program is introduced as a set of transformative steps to promote well-being and to shift fear of aging into inspiration for living well. Results: Nine steps to Grateful Aging are identified: 1) answer the call to transformation, 2) cultivate curiosity, 3) formalize a Grateful Aging practice, 4) set intention for Grateful Aging, 5) pay attention to the gifts of aging, 6) build Grateful Aging habits, 7) find guidance, 8) move to acceptance, and 9) transform self and society. Educational programs are described for elderly patients and for the health care professionals who serve them. Conclusion: The Grateful Aging Program is designed to expand awareness of healthy, mindful, and meaningful aging; to promote individual and social well-being; and to facilitate a supportive atmosphere for personal enrichment and shared learning.

  11. Testing intermediate-age stellar evolution models with VLT photometry of LMC clusters. I. The data

    CERN Document Server

    Gallart, C; Bertelli, G; Chiosi, C; Demarque, P; Girardi, L; Nasi, E; Woo, J H; Yi, S

    2003-01-01

    This is the first of a series of three papers devoted to the calibration of a few parameters of crucial importance in the modeling of the evolution of intermediate-mass stars, with special attention to the amount of convective core overshoot. To this end we acquired deep V and R photometry for three globular clusters of the Large Magellanic Cloud (LMC), namely NGC 2173, SL 556 and NGC 2155, in the age interval 1-3 Gyr. In this first paper, we describe the aim of the project, the VLT observations and data reduction, and we make preliminary comparisons of the color-magnitude diagrams with both Padova and Yonsei-Yale isochrones. Two following papers in this series present the results of a detailed analysis of these data, independently carried out by members of the Yale and Padova stellar evolution groups. This allows us to compare both sets of models and discuss their main differences, as well as the systematic effects that they would have to the determination of the ages and metallicities of intermediate-age si...

  12. Testing intermediate-age stellar evolution models with VLT photometry of LMC clusters. III. Padova results

    CERN Document Server

    Bertelli, G; Girardi, L; Chiosi, C; Zoccali, M; Gallart, C

    2002-01-01

    The color-magnitude diagrams (CMDs) of three intermediate-age LMC clusters, NGC 2173, SL556 and NGC2155 are analyzed to determine their age and metallicity basing on Padova stellar models. Synthetic CMDs are compared with cluster data. The best match is obtained using two fitting functions based on star counts in the different bins of the cluster CMD. Two different criteria are used. One of them takes into account the uncertainties in the color of the red clump stars. Given the uncertainties on the experimental values of the clusters metallicity, we provide a set of acceptable solutions. They define the correspondent values of metallicity, age, reddening and distance modulus (for the assumed IMF). The comparison with Padova models suggests for NGC 2173 a prolonged star formation (spanning a period of about 0.3 Gyr), beginning 1.7 Gyr and ending 1.4 Gyr ago. The metallicity Z is in the range 0.0016 $-$ 0.003. Contrary to what suggested for NGC 2173 a period of extended star formation was not required to fit th...

  13. Age-period-cohort modelling of breast cancer incidence in the Nordic countries

    DEFF Research Database (Denmark)

    Rostgaard, K; Vaeth, M; Holst, H;

    2001-01-01

    The Nordic countries have experienced a steady increase in breast cancer incidence throughout the past 35 years. We analysed the incidence in Denmark, Finland, Norway and Sweden during the period 1958 to 1992 using age-period-cohort models and taking the systematic mammography screening into acco...... exposed to an increasing load of cohort borne breast cancer risk factors not experienced to the same extent by Norwegian women, whereas they were seemingly subjected to the same period effects.......The Nordic countries have experienced a steady increase in breast cancer incidence throughout the past 35 years. We analysed the incidence in Denmark, Finland, Norway and Sweden during the period 1958 to 1992 using age-period-cohort models and taking the systematic mammography screening...... in breast cancer incidence seen in the Nordic countries. The widespread practice of neglecting the period effects in age-period-cohort analysis of time trends in breast cancer incidence therefore probably needs reconsideration. A key finding was that Danish women born in the 20th century seem to have been...

  14. Sizes and ages of SDSS ellipticals: Comparison with hierarchical galaxy formation models

    CERN Document Server

    Shankar, Francesco; Bernardi, Mariangela; Dai, Xinyu; Hyde, Joseph B; Sheth, Ravi K

    2009-01-01

    In a sample of about 45,700 early-type galaxies extracted from SDSS, we find that the shape, normalization, and dispersion around the mean size-stellar mass relation is the same for young and old systems, provided the stellar mass is greater than 3*10^10 Msun. This is difficult to reproduce in pure passive evolution models, which generically predict older galaxies to be much more compact than younger ones of the same stellar mass. However, this aspect of our measurements is well reproduced by hierarchical models of galaxy formation. Whereas the models predict more compact galaxies at high redshifts, subsequent minor, dry mergers increase the sizes of the more massive objects, resulting in a flat size-age relation at the present time. At lower masses, the models predict that mergers are less frequent, so that the expected anti-correlation between age and size is not completely erased. This is in good agreement with our data: below 3*10^10 Msun, the effective radius R_e is a factor of ~2 lower for older galaxie...

  15. A functional group oxidation model (FGOM for SOA formation and aging

    Directory of Open Access Journals (Sweden)

    X. Zhang

    2013-06-01

    Full Text Available Secondary organic aerosol (SOA formation from a volatile organic compound (VOC involves multiple generations of oxidation that include functionalization and fragmentation of the parent carbon backbone and likely particle-phase oxidation and/or accretion reactions. Despite the typical complexity of the detailed molecular mechanism of SOA formation and aging, a relatively small number of functional groups characterize the oxidized molecules that constitute SOA. Given the carbon number and set of functional groups, the volatility of the molecule can be estimated. We present here a functional group oxidation model (FGOM that represents the process of SOA formation and aging. The FGOM contains a set of parameters that are to be determined by fitting of the model to laboratory chamber data: total organic aerosol concentration, and O : C and H : C atomic ratios. The sensitivity of the model prediction to variation of the adjustable parameters allows one to assess the relative importance of various pathways involved in SOA formation. An analysis of SOA formation from the high- and low-NOx photooxidation of four C12 alkanes (n-dodecane, 2-methylundecane, hexylcyclohexane, and cyclododecane using the FGOM is presented, and comparison with the statistical oxidation model (SOM of Cappa et al. (2013 is discussed.

  16. A Functional Group Oxidation Model (FGOM for SOA formation and aging

    Directory of Open Access Journals (Sweden)

    X. Zhang

    2012-12-01

    Full Text Available Secondary organic aerosol (SOA formation from a volatile organic compound (VOC involves multiple generations of oxidation that include functionalization and fragmentation of the parent carbon backbone and, likely, particle-phase oxidation and/or accretion reactions. Despite the typical complexity of the detailed molecular mechanism of SOA formation and aging, a relatively small number of functional groups characterize the oxidized molecules that constitute SOA. Given the carbon number and set of functional groups, the volatility of the molecule can be estimated. We present here a Functional Group Oxidation Model (FGOM that represents the process of SOA formation and aging. The FGOM contains a set of parameters that are to be determined by fitting of the model to laboratory chamber data: total organic aerosol concentration, and O:C and H:C atomic ratios. The sensitivity of the model prediction to variation of the adjustable parameters allows one to assess the relative importance of various pathways involved in SOA formation. An analysis of SOA formation from the high- and low-NOx photooxidation of four C12 alkanes (n-dodecane, 2-methylundecane, hexylcyclohexane, and cyclododecane using the FGOM is presented, and comparison with the Statistical Oxidation Model (SOM of Cappa et al. (2012 is discussed.

  17. Optimizing a Male Reproductive Aging Mouse Model by d-Galactose Injection

    Directory of Open Access Journals (Sweden)

    Chun-Hou Liao

    2016-01-01

    Full Text Available The d-galactose (d-gal-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8–10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks. First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1 that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm

  18. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Mariarita Romanucci

    2015-01-01

    Full Text Available Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS and Heat Shock Proteins (HSPs, in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  19. Methodology for the Incorporation of Passive Component Aging Modeling into the RAVEN/ RELAP-7 Environment

    Energy Technology Data Exchange (ETDEWEB)

    Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua; Alfonsi, Andrea; Askin Guler; Tunc Aldemir

    2014-11-01

    Passive system, structure and components (SSCs) will degrade over their operation life and this degradation may cause to reduction in the safety margins of a nuclear power plant. In traditional probabilistic risk assessment (PRA) using the event-tree/fault-tree methodology, passive SSC failure rates are generally based on generic plant failure data and the true state of a specific plant is not reflected realistically. To address aging effects of passive SSCs in the traditional PRA methodology [1] does consider physics based models that account for the operating conditions in the plant, however, [1] does not include effects of surveillance/inspection. This paper represents an overall methodology for the incorporation of aging modeling of passive components into the RAVEN/RELAP-7 environment which provides a framework for performing dynamic PRA. Dynamic PRA allows consideration of both epistemic and aleatory uncertainties (including those associated with maintenance activities) in a consistent phenomenological and probabilistic framework and is often needed when there is complex process/hardware/software/firmware/ human interaction [2]. Dynamic PRA has gained attention recently due to difficulties in the traditional PRA modeling of aging effects of passive components using physics based models and also in the modeling of digital instrumentation and control systems. RAVEN (Reactor Analysis and Virtual control Environment) [3] is a software package under development at the Idaho National Laboratory (INL) as an online control logic driver and post-processing tool. It is coupled to the plant transient code RELAP-7 (Reactor Excursion and Leak Analysis Program) also currently under development at INL [3], as well as RELAP 5 [4]. The overall methodology aims to: • Address multiple aging mechanisms involving large number of components in a computational feasible manner where sequencing of events is conditioned on the physical conditions predicted in a simulation

  20. Age models for peat deposits on the basis of coupled lead-210 and radiocarbon data.

    Science.gov (United States)

    Piotrowska, Natalia; de Vleeschouwer, François; Sikorski, Jarosław; Sensuła, Barbara; Michczyński, Adam; Fiałkiewicz-Kozieł, Barbara; Palowski, Bernard

    2010-05-01

    The study presents three examples of age-model construction based on the results of 210Pb and 14C dating methods applied to peat deposits. The three sites are ombrotrophic peat bogs: the Misten (Belgium), Slowinskie Bloto (N Poland) and Puscizna Mala (S Poland). All sites have been subjected to multiproxy studies aimed at reconstructing paleoenvironment and human activity, covering the last 1500, 1300 and 1800 years, respectively (De Vleeschouwer et al. 2009A, 2009B, in prep., Fialkiewicz-Koziel, ongoing PhD). A detailed comparison between 210Pb and post-bomb 14C results in the Misten bog has also been carried out by Piotrowska et al. (2009). In all cores, the 210Pb activity was calculated using 210Po and 208Po activities after acid-extraction from bulk samples, subsequent deposition on silver discs and measurements by alpha spectrometry. Unsupported 210Pb was detected until 35cm in Slowinskie Bloto, 15cm in the Misten and 19cm in Puscizna Mala. Constant Rate of Supply (CRS) model was then applied to compute ages of each 1-cm core interval. For the Misten and Slowinskie Bloto, radiocarbon measurements were performed on selected aboveground plant macrofossils, mainly Sphagnum spp. or Calluna vulgaris, Erica tetralix, and Andromeda polyfolia. Radiocarbon ages were determined using accelerator mass spectrometry (AMS) after acid-alkali-acid wash, combustion, purification of carbon dioxide and graphitisation. For Puscizna Mala bulk samples were dated after chemical preparation of benzene for liquid scintillation counting (LSC) or CO2 for gas proportional counting (GPC). Radiocarbon calibration was undertaken using the Intcal04 calibration curve and OxCal 4 software. As a priori information the 210Pb-derived ages were used in a P_Sequence model (Bronk Ramsey, 2008). A number of dates characterized by low agreement with stratigraphical order had to be considered as outliers and rejected from the final age model. For building a continuous age models a non-linear approach

  1. Modelling the Effects of Ageing Time of Starch on the Enzymatic Activity of Three Amylolytic Enzymes

    Directory of Open Access Journals (Sweden)

    Nelson P. Guerra

    2012-01-01

    Full Text Available The effect of increasing ageing time (t of starch on the activity of three amylolytic enzymes (Termamyl, San Super, and BAN was investigated. Although all the enzymatic reactions follow michaelian kinetics, vmax decreased significantly (P<0.05 and KM increased (although not always significantly with the increase in t. The conformational changes produced in the starch chains as a consequence of the ageing seemed to affect negatively the diffusivity of the starch to the active site of the enzymes and the release of the reaction products to the medium. A similar effect was observed when the enzymatic reactions were carried out with unaged starches supplemented with different concentrations of gelatine [G]. The inhibition in the amylolytic activities was best mathematically described by using three modified forms of the Michaelis-Menten model, which included a term to consider, respectively, the linear, exponential, and hyperbolic inhibitory effects of t and [G].

  2. Constraining stellar population models - I. Age, metallicity, and abundance pattern compilation for Galactic globular clusters

    CERN Document Server

    Roediger, Joel C; Graves, Genevieve; Schiavon, Ricardo

    2013-01-01

    We present an extenstive literature compilation of age, metallicity, and chemical abundance pattern information for the 41 Galactic globular clusters (GGCs) studied by Schiavon et al. (2005). Our compilation constitutes a notable improvement over previous similar work, particularly in terms of chemical abundances. Its primary purpose is to enable detailed evaluations of and refinements to stellar population synthesis models designed to recover the above information for unresolved stellar systems based on their integrated spectra. However, since the Schiavon sample spans a wide range of the known GGC parameter space, our compilation may also benefit investigations related to a variety of astrophysical endeavours, such as the early formation of the Milky Way, the chemical evolution of GGCs, and stellar evolution and nucleosynthesis. For instance, we confirm with our compiled data that the GGC system has a bimodal metallicity distribution and is uniformly enhanced in the alpha-elements. When paired with the ages...

  3. An additional planet as a model for the Pleistocene Ice Age

    CERN Document Server

    Wölfli, W; Nufer, R

    2002-01-01

    We propose a model for the Pleistocene Ice Age, assuming the following scenario: Between 3 Myr and 11.5 kyr BP a Mars-sized object existed which moved in a highly eccentric orbit. Originating from this object, gas clouds with a complex dynamics reduced Earth's insolation and caused a drop in the global temperature. In a close encounter, 11.5 kyr ago, tidal forces deformed the Earth. While the shape of the gyroscope Earth relaxed, the North Pole moved geographically from Greenland to its present position. During this close encounter, the object was torn to pieces, each of which subsequently evaporated or plunged into the sun. These events terminated the Ice Age Epoch.

  4. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

    Science.gov (United States)

    Forman, Katherine; Vara, Elena; García, Cruz; Kireev, Roman; Cuesta, Sara; Acuña-Castroviejo, Darío; Tresguerres, J A F

    2010-10-01

    This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.

  5. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's disease

    Science.gov (United States)

    Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

    2014-01-01

    Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019

  6. Calculation models for prediction of Liquefied Natural Gas (LNG) ageing during ship transportation

    Energy Technology Data Exchange (ETDEWEB)

    Miana, Mario; Hoyo, Rafael del; Rodrigalvarez, Vega; Valdes, Jose Ramon [Instituto Tecnologico de Aragon, Area de Investigacion, Desarrollo y Servicios Tecnologicos, Maria de Luna 7, 50018 Zaragoza (Spain); Llorens, Raul [ENAGAS SA, Direccion de Ingenieria y Tecnologia del Gas, Autovia A - 2, km. 306.4, 50012 Zaragoza (Spain)

    2010-05-15

    A group of European gas transportation companies within the European Gas Research Group launched in 2007 the 'MOLAS' Project to provide a software program for the analysis of the Liquefied Natural Gas (LNG) ageing process during ship transportation. This program contains two different modeling approaches: a physical algorithm and an 'intelligent' model. Both models are fed with the same input data, which is composed of the ship characteristics (BOR and capacity), voyage duration, LNG composition, temperature, pressure, and volume occupied by liquid phase at the port of origin, together with pressure at the port of destination. The results obtained are the LNG composition, temperature and liquid volume at the port of destination. Furthermore, the physical model obtains the evolution over time of such variables en route as it is based on unsteady mass balances over the system, while the i-model applies neural networks to obtain regression coefficients from historical data composed only of origin and destination measurements. This paper describes both models and validates them from previous published models and experimental data measured in ENAGAS LNG regasification plants. (author)

  7. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling.

    Science.gov (United States)

    González, Oscar C; Krishnan, Giri P; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence; Bazhenov, Maxim

    2015-09-30

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. Significance statement: Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy.

  8. Reliability of some ageing nuclear power plant system: a simple stochastic model

    Energy Technology Data Exchange (ETDEWEB)

    Suarez-Antola, Roberto [Catholic University of Uruguay, Montevideo (Uruguay). School of Engineering and Technologies; Ministerio de Industria, Energia y Mineria, Montevideo (Uruguay). Direccion Nacional de Energia y Tecnologia Nuclear; E-mail: rsuarez@ucu.edu.uy

    2007-07-01

    The random number of failure-related events in certain repairable ageing systems, like certain nuclear power plant components, during a given time interval, may be often modelled by a compound Poisson distribution. One of these is the Polya-Aeppli distribution. The derivation of a stationary Polya-Aeppli distribution as a limiting distribution of rare events for stationary Bernouilli trials with first order Markov dependence is considered. But if the parameters of the Polya-Aeppli distribution are suitable time functions, we could expect that the resulting distribution would allow us to take into account the distribution of failure-related events in an ageing system. Assuming that a critical number of damages produce an emergent failure, the above mentioned results can be applied in a reliability analysis. It is natural to ask under what conditions a Polya-Aeppli distribution could be a limiting distribution for non-homogeneous Bernouilli trials with first order Markov dependence. In this paper this problem is analyzed and possible applications of the obtained results to ageing or deteriorating nuclear power plant components are considered. The two traditional ways of modelling repairable systems in reliability theory: the 'as bad as old' concept, that assumes that the replaced component is exactly under the same conditions as was the aged component before failure, and the 'as good as new' concept, that assumes that the new component is under the same conditions of the replaced component when it was new, are briefly discussed in relation with the findings of the present work. (author)

  9. Relationship between the complement system, risk factors and prediction models in age-related macular degeneration.

    Science.gov (United States)

    Bora, Nalini S; Matta, Bharati; Lyzogubov, Valeriy V; Bora, Puran S

    2015-02-01

    Studies performed over the past decade in humans and experimental animals have been a major source of information and improved our understanding of how dysregulation of the complement system contributes to age-related macular degeneration (AMD) pathology. Drusen, the hall-mark of dry-type AMD are reported to be the by-product of complement mediated inflammatory processes. In wet AMD, unregulated complement activation results in increased production of angiogenic growth factors leading to choroidal neovascularization both in humans and in animal models. In this review article we have linked the complement system with modifiable and non-modifiable AMD risk factors as well as with prediction models of AMD. Understanding the association between the complement system, risk factors and prediction models will help improve our understanding of AMD pathology and management of this disease.

  10. Parametric optimization of friction stir welding process of age hardenable aluminum alloys-ANFIS modeling

    Institute of Scientific and Technical Information of China (English)

    D Vijayan; V Seshagiri Rao

    2016-01-01

    A comparative approach was performed between the response surface method (RSM) and the adaptive neuro-fuzzy inference system (ANFIS) to enhance the tensile properties, including the ultimate tensile strength and the tensile elongation, of friction stir welded age hardenable AA6061 and AA2024 aluminum alloys. The effects of the welding parameters, namely the tool rotational speed, welding speed, axial load and pin profile, on the ultimate tensile strength and the tensile elongation were analyzed using a three-level, four-factor Box-Behnken experimental design. The developed design was utilized to train the ANFIS models. The predictive capabilities of RSM and ANFIS were compared based on the root mean square error, the mean absolute error, and the correlation coefficient based on the obtained data set. The results demonstrate that the developed ANFIS models are more effective than the RSM model.

  11. Fourth-Order Method for Numerical Integration of Age- and Size-Structured Population Models

    Energy Technology Data Exchange (ETDEWEB)

    Iannelli, M; Kostova, T; Milner, F A

    2008-01-08

    In many applications of age- and size-structured population models, there is an interest in obtaining good approximations of total population numbers rather than of their densities. Therefore, it is reasonable in such cases to solve numerically not the PDE model equations themselves, but rather their integral equivalents. For this purpose quadrature formulae are used in place of the integrals. Because quadratures can be designed with any order of accuracy, one can obtain numerical approximations of the solutions with very fast convergence. In this article, we present a general framework and a specific example of a fourth-order method based on composite Newton-Cotes quadratures for a size-structured population model.

  12. Modeling and prediction of HIV in China: transmission rates structured by infection ages.

    Science.gov (United States)

    Zhou, Yican; Shao, Yiming; Ruan, Yuhua; Xu, Jianqing; Ma, Zhien; Mei, Changlin; Wu, Jianhong

    2008-04-01

    HIV transmission process involves a long incubation and infection period, and the transmission rate varies greatly with infection stage. Consequently, modeling analysis based on the assumption of a constant transmission rate during the entire infection period yields an inaccurate description of HIV transmission dynamics and long-term projections. Here we develop a general framework of mathematical modeling that takes into account this heterogeneity of transmission rate and permits rigorous estimation of important parameters using a regression analysis of the twenty-year reported HIV infection data in China. Despite the large variation in this statistical data attributable to the knowledge of HIV, surveillance efforts, and uncertain events, and although the reported data counts individuals who might have been infected many years ago, our analysis shows that the model structured on infection age can assist us in extracting from this data set very useful information about transmission trends and about effectiveness of various control measures.

  13. Anti-Skin-Aging Effect of Epigallocatechin Gallate by Regulating Epidermal Growth Factor Receptor Pathway on Aging Mouse Model Induced by D-Galactose.

    Science.gov (United States)

    Chen, Jiming; Li, Yifan; Zhu, Qiangqiang; Li, Tong; Lu, Hao; Wei, Nan; Huang, Yewei; Shi, Ruoyu; Ma, Xiao; Wang, Xuanjun; Sheng, Jun

    2017-03-23

    Epigallocatechin gallate(EGCG) is a monomer separated from tea catechins, as an well-known antioxidant, which helps fight wrinkles and rejuvenate skin cells. In this study, we investigated the anti-aging effect of EGCG, and to clarify underlying mechanism of skin aging in a D-galactose-induced aging mouse model. Forty-five male mice were divided into 5 groups and treated with different dose of EGCG, Vitamin C (VitC) to mice as a positive control. All groups except vehicle were established aging model induced by D-galactose (200mg/kg/day) that was subcutaneously injected to mice for 8 weeks. Two weeks after injection of D-galactose, EGCG and Vit C groups were simultaneously administered once a day by subcutaneously inject after 5hours for injecting D-galactose. The results show that EGCG can be absorbed by the skin. Overall, the conditions of the skin of EGCG-treatment groups were improved, the whole structure of skin were better than control groups, and the levels of oxidative stress and the expression of relate with EGFR proteins were significantly higher than control group after EGCG treatment. All these findings suggest that EGCG can resist skin senility effectively. And the EGFR with relate of downstream proteins are implicated in the skin aging.

  14. Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

    Science.gov (United States)

    Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

    2014-11-01

    Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

  15. Models for estimating the metabolic syndrome biological age as the new index for evaluation and management of metabolic syndrome

    Science.gov (United States)

    Kang, Young Gon; Suh, Eunkyung; Chun, Hyejin; Kim, Sun-Hyun; Kim, Deog Ki; Bae, Chul-Young

    2017-01-01

    Purpose This study aims to propose a metabolic syndrome (MS) biological age model, through which overall evaluation and management of the health status and aging state in MS can be done easily. Through this model, we hope to provide a novel evaluation and management health index that can be utilized in various health care fields. Patient and methods MS parameters from American Heart Association/National Heart, Lung, and Blood Institute guidelines in 2005 were used as biomarkers for the estimation of MS biological age. MS biological age model development was done by analyzing data of 263,828 participants and clinical application of the developed MS biological age was assessed by analyzing the data of 188,886 subjects. Results The principal component accounted for 36.1% in male and 38.9% in female of the total variance in the battery of five variables. The correlation coefficient between corrected biological age and chronological age in males and females were 0.711 and 0.737, respectively. Significant difference for mean MS biological age and chronological age between the three groups, normal, at risk and MS, was seen (P<0.001). Conclusion For the comprehensive approach in MS management, MS biological age is expected to be additionally utilized as a novel evaluation and management index along with the traditional MS diagnosis. PMID:28203066

  16. Classifying human audiometric phenotypes of age-related hearing loss from animal models.

    Science.gov (United States)

    Dubno, Judy R; Eckert, Mark A; Lee, Fu-Shing; Matthews, Lois J; Schmiedt, Richard A

    2013-10-01

    Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations ("audiometric phenotypes"). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for "exemplars" (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.

  17. The integrate model of emotion, thinking and self regulation: an application to the "paradox of aging".

    Science.gov (United States)

    Williams, Leanne M; Gatt, Justine M; Hatch, Ainslie; Palmer, Donna M; Nagy, Marie; Rennie, Christopher; Cooper, Nicholas J; Morris, Charlotte; Grieve, Stuart; Dobson-Stone, Carol; Schofield, Peter; Clark, C Richard; Gordon, Evian; Arns, Martijn; Paul, Robert H

    2008-09-01

    This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.

  18. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Directory of Open Access Journals (Sweden)

    Lingling Zeng

    Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  19. Development of a lifetime prediction model for lithium-ion batteries based on extended accelerated aging test data

    Science.gov (United States)

    Ecker, Madeleine; Gerschler, Jochen B.; Vogel, Jan; Käbitz, Stefan; Hust, Friedrich; Dechent, Philipp; Sauer, Dirk Uwe

    2012-10-01

    Battery lifetime prognosis is a key requirement for successful market introduction of electric and hybrid vehicles. This work aims at the development of a lifetime prediction approach based on an aging model for lithium-ion batteries. A multivariable analysis of a detailed series of accelerated lifetime experiments representing typical operating conditions in hybrid electric vehicle is presented. The impact of temperature and state of charge on impedance rise and capacity loss is quantified. The investigations are based on a high-power NMC/graphite lithium-ion battery with good cycle lifetime. The resulting mathematical functions are physically motivated by the occurring aging effects and are used for the parameterization of a semi-empirical aging model. An impedance-based electric-thermal model is coupled to the aging model to simulate the dynamic interaction between aging of the battery and the thermal as well as electric behavior. Based on these models different drive cycles and management strategies can be analyzed with regard to their impact on lifetime. It is an important tool for vehicle designers and for the implementation of business models. A key contribution of the paper is the parameterization of the aging model by experimental data, while aging simulation in the literature usually lacks a robust empirical foundation.

  20. Aging and orthopedics: how a lifespan development model can inform practice and research.

    Science.gov (United States)

    Gautreau, Sylvia; Gould, Odette N; Forsythe, Michael E

    2016-08-01

    Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses that need to be managed over the lifespan. The result is an ongoing shift from curing acute illnesses to the management and care of chronic illness and conditions. Theoretical models that provide a useful and feasible vision for the future of health care and health care research are needed. This review discusses how the lifespan development model used in some disciplines within the behavioural sciences can be seen as an extension of the biopsychosocial model. We posit that the lifespan development model provides useful perspectives for both orthopedic care and research. We present key concepts and recommendations, and we discuss how the lifespan development model can contribute to new and evolving perspectives on orthopedic outcomes and to new directions for research. We also offer practical guidelines on how to implement the model in orthopedic practice.

  1. Testing models of psychopathology in preschool-aged children using a structured interview-based assessment.

    Science.gov (United States)

    Olino, Thomas M; Dougherty, Lea R; Bufferd, Sara J; Carlson, Gabrielle A; Klein, Daniel N

    2014-10-01

    A number of studies have found that broadband internalizing and externalizing factors provide a parsimonious framework for understanding the structure of psychopathology across childhood, adolescence, and adulthood. However, few of these studies have examined psychopathology in young children, and several recent studies have found support for alternative models, including a bi-factor model with common and specific factors. The present study used parents' (typically mothers') reports on a diagnostic interview in a community sample of 3-year old children (n = 541; 53.9 % male) to compare the internalizing-externalizing latent factor model with a bi-factor model. The bi-factor model provided a better fit to the data. To test the concurrent validity of this solution, we examined associations between this model and paternal reports and laboratory observations of child temperament. The internalizing factor was associated with low levels of surgency and high levels of fear; the externalizing factor was associated with high levels of surgency and disinhibition and low levels of effortful control; and the common factor was associated with high levels of surgency and negative affect and low levels of effortful control. These results suggest that psychopathology in preschool-aged children may be explained by a single, common factor influencing nearly all disorders and unique internalizing and externalizing factors. These findings indicate that shared variance across internalizing and externalizing domains is substantial and are consistent with recent suggestions that emotion regulation difficulties may be a common vulnerability for a wide array of psychopathology.

  2. Two cosmological models, the age of the Universe, and dark energy

    CERN Document Server

    Chaliasos, E

    2004-01-01

    The prevailing cosmological model with the lambda-term, in which the space is flat, is studied (section 1). The corresponding age of the Universe (t0) is calculated (assuming a Hubble constant consistent with the measurements of the Hubble telescope), as well as the deceleration parameter (q0). The latter is found negative, showing an accelerating Universe, but the former is insufficient to account for the actually estimated value. Nevertheless, with more recent values of the parameters involved, this model actually gives a result consistent with the estimated value. But there is a severe defect in the prevailing model, concerning the so-called dark energy, necessary to be introduced. Then, another model without the lambda-term, and based on the time-symmetric theory of the author, is studied (section 3), after an introduction to this theory (section 2). In this model the space is open, but the overall space-time is flat. It is not accelerating (it retains a constant rate of expansion). In this model, with q0...

  3. An endogenous retrovirus and exogenous scrapie in a mouse model of aging.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Kozlowski, I; Sersen, E A

    2000-01-01

    As we enter the post-genomic era, there is an increasing need for accurate methods of identifying host and pathogen factors that contribute to bacterial, viral and fungal disease. In addition, there is a requirement for fast and precise techniques to evaluate potential therapies for the prevention of infectious diseases. The development of useful and cost-effective model systems will be crucial in advancing our knowledge of all aspects of microbial pathogenesis. In this series, we will learn of animal models used to investigate diseases caused by a wide variety of pathogens, including HIV, Vibrio cholerae and Pseudomonas aeruginosa. A description of a model system specifically designed to study intracellular pathogens will be presented, as will a variety of the techniques currently used to exploit other useful models of infection. Additionally, a description of the mathematical models used to analyse the population biology of human onchocerciasis will be discussed. The series begins with an intriguing look at the possible connections between an endogenous retrovirus, the infectious agent of scrapie and accelerated senescence in a mouse model of early aging.

  4. Structurally functional model of socially valuable behavior of children at the stage of transition from the senior preschool age to primary school age

    Directory of Open Access Journals (Sweden)

    Elvira Bakhteeva

    2013-11-01

    Full Text Available The author analyses the transition period from the senior preschool age to primary school age as optimum for development of preconditions of stable social behavior of the child. Special attention is given to the background of leading value of children's subculture in formation of experience of social behavior of 5–7 year old children. On the basis of the research, carried out by the author, the essence of the concept “socially-valuable behavior” is revealed. The components and structurally functional model of socially-valuable behavior are presented.

  5. Modeling of Late Blooming Phases and Precipitation Kinetics in Aging Reactor Pressure Vessel (RPV) Steels

    Energy Technology Data Exchange (ETDEWEB)

    Yongfeng Zhang; Pritam Chakraborty; S. Bulent Biner

    2013-09-01

    The principle work at the atomic scale is to develop a predictive quantitative model for the microstructure evolution of RPV steels under thermal aging and neutron radiation. We have developed an AKMC method for the precipitation kinetics in bcc-Fe, with Cu, Ni, Mn and Si being the alloying elements. In addition, we used MD simulations to provide input parameters (if not available in literature). MMC simulations were also carried out to explore the possible segregation/precipitation morphologies at the lattice defects. First we briefly describe each of the simulation algorithms, then will present our results.

  6. Latency-aged children with attachment disturbances: a conjoint treatment model.

    Science.gov (United States)

    Shiller, Virginia M

    2011-01-01

    Psychoanalytic theory and practice has increasingly accepted the importance of attachment relationships in psychic development. However, there have been only very limited efforts to develop psychoanalytically informed interventions for older adopted and foster children who show significant disturbances in attachment. This paper reviews theory and research that lays groundwork for a framework for conceptualizing treatment needs for attachment disordered children. Two cases of conjoint work with parents and their latency age sons are presented. The treatment cases highlight the importance of work to increase parents' reflective functioning capacities and the need to challenge children's defensively excluded early internal working models of self and caregivers.

  7. Measurement and modeling of engineered nanoparticle transport and aging dynamics in a reactive porous medium

    Science.gov (United States)

    Naftaly, Aviv; Dror, Ishai; Berkowitz, Brian

    2016-07-01

    A continuous time random walk particle tracking (CTRW-PT) method was employed to model flow cell experiments that measured transport of engineered nanoparticles (ENPs) in a reactive porous medium. The experiments involved a water-saturated medium containing negatively charged, polyacrylamide beads, resembling many natural soils and aquifer materials, and having the same refraction index as water. Negatively and positively charged ENPs were injected into a uniform flow field in a 3-D horizontal flow cell, and the spatial and temporal concentrations of the evolving ENP plumes were obtained via image analysis. As a benchmark, and to calibrate the model, Congo red tracer was employed in 1-D column and 3-D flow cell experiments, containing the same beads. Negatively charged Au and Ag ENPs demonstrated migration patterns resembling those of the tracer but were slightly more dispersive; the transport was well represented by the CTRW-PT model. In contrast, positively charged AgNPs displayed an unusual behavior: establishment of an initial plume of essentially immobilized ENPs, followed by development of a secondary, freely migrating plume. The mobile plume was found to contain ENPs that, with aging, exhibited aggregation and charge inversion, becoming negatively charged and mobile. In this case, the CTRW-PT model was modified to include a probabilistic law for particle immobilization, to account for the decreasing tendency (over distance and time) of the positively charged AgNPs to attach to the porous medium. The agreement between experimental results and modeling suggests that the CTRW-PT framework can account for the non-Fickian and surface-charge-dependent transport and aging exhibited by ENPs in porous media.

  8. Modelling realistic horizontal branch morphologies and their impact on spectroscopic ages of unresolved stellar systems

    Science.gov (United States)

    Percival, Susan M.; Salaris, Maurizio

    2011-04-01

    The presence of an extended blue horizontal branch (HB) in a stellar population is known to affect the age inferred from spectral fitting to stellar population synthesis models. This is due to the hot blue component which increases the strength of the Balmer lines and can make an old population look spuriously young. However, most population synthesis models still rely on theoretical isochrones, which do not include realistic modelling of extended HBs. In this work, we create detailed models for a range of old simple stellar populations (SSPs), with metallicities ranging from [Fe/H]=-1.3 to solar, to create a variety of realistic HB morphologies, from extended red clumps, to extreme blue HBs. We achieve this by utilizing stellar tracks from the BaSTI data base and implementing a different mass-loss prescription for each SSP created. This includes setting an average mass and a Gaussian spread in masses of individual stars coming on to the zero-age HB for each model, and hence resulting in different HB morphologies. We find that, for each metallicity, there is some HB morphology which maximizes Hβ, making an underlying 14-Gyr population look ˜5-6 Gyr old for the low- and intermediate-metallicity cases, and as young as 2 Gyr in the case of the solar metallicity SSP. We explore whether there are any spectral indices capable of breaking the degeneracy between an old SSP with extended blue HB and a truly young or intermediate-age SSP, and find that the Ca II index of Rose and the strength of the Mg II doublet at 2800 Å are promising candidates, in combination with Hβ and other metallicity indicators, such as Mgb and Fe5406. We also run Monte Carlo simulations to investigate the level of statistical fluctuations in the spectra of typical stellar clusters. We find that fluctuations in spectral indices are significant even for average to large globular clusters and that various spectral indices are affected in different ways, which has implications for full

  9. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging.

    Directory of Open Access Journals (Sweden)

    Tjakko J van Ham

    2008-03-01

    Full Text Available Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders.

  10. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model

    Directory of Open Access Journals (Sweden)

    Christopher P. Ardeljan

    2014-12-01

    Full Text Available The etiology of Age-related Macular Degeneration (AMD remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope—particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death.

  11. Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model.

    Science.gov (United States)

    Du, Heng; Guo, Lan; Zhang, Wensheng; Rydzewska, Monika; Yan, Shidu

    2011-03-01

    Mitochondrial stress is one of the early features of Alzheimer disease (AD). Mitochondrial Aβ has been linked to mitochondrial toxicity. Our recent study demonstrated that cyclophilin D (CypD) mediated mitochondrial permeability transition pore (mPTP) is an important mechanism for neuronal and synaptic stress induced by both Aβ and oxidative stress. In transgenic AD-type mice overexpressing mutant amyloid precursor protein (APP) and Aβ (mAPP), CypD deficiency improves mitochondrial and synaptic function and learning/memory up to 12 months old. Here we provide evidence of the protective effects of CypD deficiency in aged AD mice (22-24 months). Cyp D deficient mAPP mice demonstrate less calcium-induced mitochondrial swelling, increased mitochondrial calcium uptake capacity, preserved mitochondrial respiratory function and improved spatial learning/memory even in old age (known to be the age for late stage AD pathology and synaptic dysfunction). These data demonstrate that abrogation of CypD results in persistent life-long protection against Aβ toxicity in an Alzheimer's disease mouse model, thereby suggesting that blockade of CypD may be of benefit for Alzheimer disease treatment.

  12. Age-dependent diastolic heart failure in an in vivo Drosophila model

    Science.gov (United States)

    Klassen, Matthew P; Peters, Christian J; Zhou, Shiwei; Williams, Hannah H; Jan, Lily Yeh; Jan, Yuh Nung

    2017-01-01

    While the signals and complexes that coordinate the heartbeat are well established, how the heart maintains its electromechanical rhythm over a lifetime remains an open question with significant implications to human health. Reasoning that this homeostatic challenge confronts all pulsatile organs, we developed a high resolution imaging and analysis toolset for measuring cardiac function in intact, unanesthetized Drosophila melanogaster. We demonstrate that, as in humans, normal aging primarily manifests as defects in relaxation (diastole) while preserving contractile performance. Using this approach, we discovered that a pair of two-pore potassium channel (K2P) subunits, largely dispensable early in life, are necessary for terminating contraction (systole) in aged animals, where their loss culminates in fibrillatory cardiac arrest. As the pumping function of its heart is acutely dispensable for survival, Drosophila represents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging. DOI: http://dx.doi.org/10.7554/eLife.20851.001 PMID:28328397

  13. Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

    Science.gov (United States)

    Chollet, François

    2013-03-01

    Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

  14. Thermal characterization and model free kinetics of aged epoxies and foams using TGA and DSC methods.

    Energy Technology Data Exchange (ETDEWEB)

    Cordaro, Joseph Gabriel; Kruizenga, Alan Michael; Nissen, April

    2013-10-01

    Two classes of materials, poly(methylene diphenyl diisocyanate) or PMDI foam, and cross-linked epoxy resins, were characterized using thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC), to help understand the effects of aging and %E2%80%9Cbake-out%E2%80%9D. The materials were evaluated for mass loss and the onset of decomposition. In some experiments, volatile materials released during heating were analyzed via mass spectroscopy. In all, over twenty materials were evaluated to compare the mass loss and onset temperature for decomposition. Model free kinetic (MFK) measurements, acquired using variable heating rate TGA experiments, were used to calculate the apparent activation energy of thermal decomposition. From these compiled data the effects of aging, bake-out, and sample history on the thermal stability of materials were compared. No significant differences between aged and unaged materials were detected. Bake-out did slightly affect the onset temperature of decomposition but only at the highest bake-out temperatures. Finally, some recommendations for future handling are made.

  15. The structure of optimal time- and age-dependent harvesting in the Lotka-McKendrik population model.

    Science.gov (United States)

    Hritonenko, Natali; Yatsenko, Yuri

    2007-07-01

    The paper analyzes optimal harvesting of age-structured populations described by the Lotka-McKendrik model. It is shown that the optimal time- and age-dependent harvesting control involves only one age at natural conditions. This result leads to a new optimization problem with the time-dependent harvesting age as an unknown control. The integral Lotka model is employed to explicitly describe the time-varying age of harvesting. It is proven that in the case of the exponential discounting and infinite horizon the optimal strategy is a stationary solution with a constant harvesting age. A numeric example on optimal forest management illustrates the theoretical findings. Discussion and interpretation of the results are provided.

  16. The Gene Expression Profile of D-galactose Induced Aging Model Rat Using cDNA Microarray

    Institute of Scientific and Technical Information of China (English)

    Li Min(李珉); Wang Gang; Zhang Wei; Wang Miqu; Zhang Yizheng

    2004-01-01

    In order to study the molecular mechanism of D-galactose induced aging model, cDNA microarray is used to analyze gene expression profiles of both normal and D-galactose induced aging model rats. D-galactose induced aging model rats are injected with D-galactose, while normal rats are injected with physiological saline as control. After 7 weeks, the two groups of rats are killed simultaneously. Their livers are harvested for genome-wide expression analysis. D-galactose treated rats showed changes in gene expression associated with increase or decrease in xenobiotic metabolism, protein metabolism and energy metabolism.

  17. Self-organized Criticality in an Integrate-and-Fire Neuron Model Based on Modified Aging Networks

    Institute of Scientific and Technical Information of China (English)

    LIN Min; WANG Gang; CHEN Tian-Lun

    2007-01-01

    Based on an integrate-and-fire mechanism,we investigate self-organized criticality of a simple neuron model on a modified BA scale-free network with aging nodes.In our model,we find that the distribution of avalanche size follows power-law behavior.The critical exponent (τ) depends on the aging exponent α.The structures of the network with aging of nodes change with an increase of α.The different topological structures lead to different behaviors in models of integrate-and-fire neurons.

  18. The functional age of hearing loss in a mouse model of presbycusis. I. Behavioral assessments.

    Science.gov (United States)

    Prosen, Cynthia A; Dore, Dawn J; May, Bradford J

    2003-09-01

    Presbycusis is a common form of hearing loss that progresses from high to low frequencies with advancing age. C57BL/6J mice experience a rapid progression of presbycusis-like hearing deficits and thus provide a convenient animal model for evaluating behavioral, physiological and anatomical correlates of the disorder. Previous studies of C57BL/6J mice have relied on short-term observations of age-matched subject groups to reconstruct a time course for auditory pathologies. Such statistical approaches are weakened by the variability of hearing thresholds in young mice and the inconsistent timing of degenerative effects in older mice. The present study was designed to resolve these ambiguities by tracking the hearing abilities of individual C57BL/6J mice from age 16 weeks until the onset of hearing loss in specific listening conditions. Testing at frequencies of 8 and 16 kHz in quiet confirmed the high-to-low frequency progression that is characteristic of presbycusis. Often the hearing loss developed in two phases, one gradual and the other abrupt. Testing in noise revealed deficits that were first manifested as threshold instability and then an increased susceptibility to masking. These changes occurred before hearing loss in quiet. CBA/CaJ mice did not show significant loss during a similar period of observation. Our findings provide a well-ordered chronology for isolating the functional consequences of multiple cochlear pathologies that arise during the time course of presbycusis. This neurobehavioral assessment is termed the functional age of hearing loss. Neuroanatomical assessments of behaviorally characterized C57BL/6J mice are presented in the companion paper [Hear. Res. 183 (2003) 29-36].

  19. Carcinogenically relevant split dose repair increased with age in rat skin model.

    Science.gov (United States)

    Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng; Uddin, Ahmed

    2012-07-01

    These experiments utilize cancer induction to evaluate cancer-relevant repair during the interval between dose fractions. Low LET electron radiation(LET ~ 0.34 keV/u) were utilized in experiments that involved exposing rat dorsal skin to 2 equal 8 Gy dose fractions separated at various intervals from 0.25 h to 24 h. Cancer onset was established for 80 weeks after the exposures and only histologically verified cancers were included in the analysis. This experiment involved a total of 540 rats and 880 induced cancers. In the youngest rats (irradiated at 28 days of age) the cancer yield declined with a halftime of approximately 3.5 hrs. In 113 day old rats the cancer yield halftime was shortened to 1.3 hrs. In the oldest rats (182 days of age), the halftime could not be established quantitatively, because it was less than the shortest interval (15 min) utilized in the protocol (best estimate ~5 min). In the oldest rats the cancer yields for all fractionated exposures dropped essentially to the expected level of 2 single fractions, below which theoretically no further reduction is possible. The follow-up times for obtaining cancer yields were the same for all exposure groups in spite of the differing ages at exposure. These results indicate that repair of carcinogenically-relevant damage accelerates with age of the rat. No information is available on the possible mechanistic basis for this finding, although the model might be useful for delineating which of the many postulated split dose repair pathways is the correct one. The finding indicates that older rats should be less susceptible to the carcinogenic action of single doses of low LET radiation in comparison to younger rats, which has been verified in separate studies.

  20. Age-structured mark-recapture analysis: A virtual-population-analysis-based model for analyzing age-structured capture-recapture data

    Science.gov (United States)

    Coggins, L.G.; Pine, William E.; Walters, C.J.; Martell, S.J.D.

    2006-01-01

    We present a new model to estimate capture probabilities, survival, abundance, and recruitment using traditional Jolly-Seber capture-recapture methods within a standard fisheries virtual population analysis framework. This approach compares the numbers of marked and unmarked fish at age captured in each year of sampling with predictions based on estimated vulnerabilities and abundance in a likelihood function. Recruitment to the earliest age at which fish can be tagged is estimated by using a virtual population analysis method to back-calculate the expected numbers of unmarked fish at risk of capture. By using information from both marked and unmarked animals in a standard fisheries age structure framework, this approach is well suited to the sparse data situations common in long-term capture-recapture programs with variable sampling effort. ?? Copyright by the American Fisheries Society 2006.

  1. A Dengue Vaccination Model for Immigrants in a Two-Age-Class Population

    Directory of Open Access Journals (Sweden)

    Hengki Tasman

    2012-01-01

    Full Text Available We develop a model of dengue transmission with some vaccination programs for immigrants. We classify the host population into child and adult classes, in regards to age structure, and into susceptible, infected and recovered compartments, in regards to disease status. Since migration plays important role in disease transmission, we include immigration and emigration factors into the model which are distributed in each compartment. Meanwhile, the vector population is divided into susceptible, exposed, and infectious compartments. In the case when there is no incoming infected immigrant, we obtain the basic reproduction ratio as a threshold parameter for existence and stability of disease-free and endemic equilibria. Meanwhile, in the case when there are some incoming infected immigrants, we obtain only endemic equilibrium. This indicates that screening for the immigrants is important to ensure the effectiveness of the disease control.

  2. Little Ice Age glaciers in Britain: Glacier–climate modelling in the Cairngorm Mountains

    Energy Technology Data Exchange (ETDEWEB)

    Stephan Harrison; Ann V. Rowan; Neil F. Glasser; Jasper Knight; Mitchell A. Plummer; Stephanie C. Mills

    2014-02-01

    It is widely believed that the last glaciers in the British Isles disappeared at the end of the Younger Dryas stadial (12.9–11.7 cal. kyr BP). Here, we use a glacier–climate model driven by data from local weather stations to show for the first time that glaciers developed during the Little Ice Age (LIA) in the Cairngorm Mountains. Our model is forced from contemporary conditions by a realistic difference in mean annual air temperature of -1.5 degrees C and an increase in annual precipitation of 10%, and confirmed by sensitivity analyses. These results are supported by the presence of small boulder moraines well within Younger Dryas ice limits, and by a dating programme on a moraine in one cirque. As a result, we argue that the last glaciers in the Cairngorm Mountains (and perhaps elsewhere in upland Britain) existed in the LIA within the last few hundred years, rather than during the Younger Dryas.

  3. Numerical Modeling of the Last Glacial Maximum Yellowstone Ice Cap Captures Asymmetry in Moraine Ages

    Science.gov (United States)

    Anderson, L. S.; Wickert, A. D.; Colgan, W. T.; Anderson, R. S.

    2014-12-01

    The Last Glacial Maximum (LGM) Yellowstone Ice Cap was the largest continuous ice body in the US Rocky Mountains. Terminal moraine ages derived from cosmogenic radionuclide dating (e.g., Licciardi and Pierce, 2008) constrain the timing of maximum Ice Cap extent. Importantly, the moraine ages vary by several thousand years around the Ice Cap; ages on the eastern outlet glaciers are significantly younger than their western counterparts. In order to interpret these observations within the context of LGM climate in North America, we perform two numerical glacier modeling experiments: 1) We model the initiation and growth of the Ice Cap to steady state; and 2) We estimate the range of LGM climate states which led to the formation of the Ice Cap. We use an efficient semi-implicit 2-D glacier model coupled to a fully implicit solution for flexural isostasy, allowing for transient links between climatic forcing, ice thickness, and earth surface deflection. Independent of parameter selection, the Ice Cap initiates in the Absaroka and Beartooth mountains and then advances across the Yellowstone plateau to the west. The Ice Cap advances to its maximum extent first to the older eastern moraines and last to the younger western and northwestern moraines. This suggests that the moraine ages may reflect the timescale required for the Ice Cap to advance across the high elevation Yellowstone plateau rather than the timing of local LGM climate. With no change in annual precipitation from the present, a mean summer temperature drop of 8-9° C is required to form the Ice Cap. Further parameter searches provide the full range of LGM paleoclimate states that led to the Yellowstone Ice Cap. Using our preferred parameter set, we find that the timescale for the growth of the complete Ice Cap is roughly 10,000 years. Isostatic subsidence helps explain the long timescale of Ice Cap growth. The Yellowstone Ice Cap caused a maximum surface deflection of 300 m (using a constant effective elastic

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

    Directory of Open Access Journals (Sweden)

    Maxim Nikolaievich Shokhirev

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

  5. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model.

    Science.gov (United States)

    Nikolaidis, Michalis G; Kyparos, Antonios; Spanou, Chrysa; Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Grivas, Gerasimos V; Zafeiridis, Andreas; Dipla, Konstantina; Vrabas, Ioannis S

    2013-08-01

    Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6±0.5 years) and ten elderly men (64.6±1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F2-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans.

  6. Immune response in virus model structured by cell infection-age.

    Science.gov (United States)

    Browne, Cameron

    2016-10-01

    This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production. The kinetics of epitope presentation and immune recognition can impact the efficacy of the immune response. We extend previous virus models to include cell infection-age structure in the infected cell compartment and immune response killing/activation rates of a PDE-ODE system. We characterize solutions to our system utilizing semigroup theory, determine equilibria and reproduction numbers, and prove stability and persistence results. Numerical simulations show that ' early immune recognition' precipitates both enhanced viral control and sustained oscillations via a Hopf bifurcation. In addition to inducing oscillatory dynamics, considering immune process rates to be functions of cell infection-age can also lead to coexistence of multiple distinct immune effector populations.

  7. Using synthetic models to simulate aging of Cu contamination in soils.

    Science.gov (United States)

    Proffit, S; Marin, B; Cances, B; Ponthieu, M; Sayen, S; Guillon, E

    2015-05-01

    The Bureau Commun de Référence (BCR) sequential extraction scheme and micro-synchrotron-based X-ray fluorescence (μ-SXRF) analysis were used to determine the Cu fractionation in a calcareous vineyard soil and a synthetic soil (mixture of seven constituents: calcite, birnessite, ferrihydrite, goethite, lignocellulosic residue, kaolinite, and quartz) at different Cu contamination rates (190, 1270, and 6350 mg kg(-1) of Cu) and aging times (1, 30, 92, and 181 days). The Cu distribution in the spiked vineyard and synthetic soils was different from the original vineyard one and was influenced by the loading level. The newly added Cu was preferentially present in the acid soluble fraction. Aging of the contaminated vineyard and synthetic soils during 6 months led to the redistribution of Cu from the weakly bound acid soluble fraction to the strongly bound reducible one. The evolution with time could satisfactorily be simulated by the Elovich diffusion model for the synthetic soils. It was less significant as less marked in the contaminated vineyard soil than in the synthetic one, even though the trends observed in both were similar. This study supported the hypothesis that "simple" synthetic models could be used to approach the Cu fractionation and its evolution with time in vineyard soils.

  8. The effects of aging on the speed-accuracy compromise: Boundary optimality in the diffusion model.

    Science.gov (United States)

    Starns, Jeffrey J; Ratcliff, Roger

    2010-06-01

    We evaluated age-related differences in the optimality of decision boundary settings in a diffusion model analysis. In the model, the width of the decision boundary represents the amount of evidence that must accumulate in favor of a response alternative before a decision is made. Wide boundaries lead to slow but accurate responding, and narrow boundaries lead to fast but inaccurate responding. There is a single value of boundary separation that produces the most correct answers in a given period of time, and we refer to this value as the reward rate optimal boundary (RROB). We consistently found across a variety of decision tasks that older adults used boundaries that were much wider than the RROB value. Young adults used boundaries that were closer to the RROB value, although age differences in optimality were smaller with instructions emphasizing speed than with instructions emphasizing accuracy. Young adults adjusted their boundary settings to more closely approach the RROB value when they were provided with accuracy feedback and extensive practice. Older participants showed no evidence of making boundary adjustments in response to feedback or task practice, and they consistently used boundary separation values that produced accuracy levels that were near asymptote. Our results suggest that young adults attempt to balance speed and accuracy to achieve the most correct answers per unit time, whereas older adultts attempt to minimize errors even if they must respond quite slowly to do so.

  9. Crust evolution in Southeast China:evidence from Nd model ages of granitoids

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Nd isotopic compositions of 58 granitoids in South China have been reported in this paper.These data together with other published data reveal that granites with Nd model ages (tDM) greater than 1.8 Ga are distributed mainly in three areas:southwestern Zhejiang-northwestern Fujian,two sides of the Wuyi Mountain and Wanyangshan-Zhuguangshan.These granites are believed to be derived from partial melting of old crust in these areas.The Mesozoic granites with tDM<1.6 Ga are distributed in three zones:the Gangang structural zone,Nanling latitudinal structural zone and Fujian-Zhejiang coastal zone.These zones may have been an extensional tectonic setting and mantle-derived components or magmas may have been involved to different extents in the granite formation.Based on Nd model ages of granites and published chronological data of mafic and ultramafic rocks,it is believed that the crust in South China experienced episodic accretions,among which the early-middle Proterozoic is the most important period of crustal accretion.

  10. Crust evolution in Southeast China: evidence from Nd model ages of granitoids

    Institute of Scientific and Technical Information of China (English)

    沈渭洲; 凌洪飞; 李武显; 王德滋

    2000-01-01

    Nd isotopic compositions of 58 granitoids in South China have been reported in this paper; These data together with other published data reveal that granites with Nd model ages (tDM) greater than 1.8 Ga are distributed mainly in three areas: southwestern Zhejiang-northwestern Fujian, two sides of the Wuyi Mountain and Wanyangshan-Zhuguangshan. These granites are believed to be derived from partial melting of old crust in these areas. The Mesozoic granites with (DM < 1.6 Ga are distributed in three zones: the Gangang structural zone, Nanling latitudinal structural zone and Fujian-Zhejiang coastal zone. These zones may have been an extensional tectonic setting and mantle-derived components or magmas may have been involved to different extents in the granite formation. Based on Nd model ages of granites and published chronological data of mafic and ultramafic rocks, it is believed that the crust in South China experienced episodic accretions, among which the early-middle Proterozoic is the most important p

  11. Circadian typology, age, and the alternative five-factor personality model in an adult women sample.

    Science.gov (United States)

    Muro, Anna; Gomà-i-Freixanet, Montserrat; Adan, Ana; Cladellas, Ramon

    2011-10-01

    Research on personality and circadian typology indicates evening-type women are more impulsive and novelty seeking, neither types are more anxious, and morning types tend to be more active, conscientious, and persistent. The purpose of this study is to examine the differences between circadian typologies in the light of the Zuckerman's Alternative Five-Factor Model (AFFM) of personality, which has a strong biological basis, in an adult sample of 412 women 18 to 55 yrs of age. The authors found morning-type women had significant higher scores than evening-type and neither-type women on Activity, and its subscales General Activity and Work Activity. In contrast, evening-type women scored significantly higher than morning-type women on Aggression-Hostility, Impulsive Sensation Seeking, and its subscale Sensation Seeking. In all groups, results were independent of age. These findings are in accordance with those previously obtained in female student samples and add new data on the AFFM. The need of using personality models that are biologically based in the study of circadian rhythms is discussed.

  12. Faculties of Education in Traditional Universities and Universities of the Third Age: A Partnership Model in Gerontagogy

    Science.gov (United States)

    Lemieux, Andre; Boutin, Gerald; Riendeau, Jean

    2007-01-01

    This article discusses "Universities of the Third Age", whose function is quite distinct from established universities' traditional role in teaching, research, and community services. Consequently, there is an urgent need to develop a model of partnership between traditional universities and Universities of the Third Age, ensuring better training…

  13. Diagnosis of hepatic fibrosis in hepatitis B patients by logistic regression modeling based on plasma amino acid ratio and age

    Institute of Scientific and Technical Information of China (English)

    张占卿

    2013-01-01

    Objective To explore the efficacy of logistic regression modeling based on plasma amino acid profile and patient age,for diagnosing hepatic fibrosis in patients with chronic hepatitis B (CHB) .Methods One-hundredand-forty-eight patients (108 males;mean age:38.1±11.9 years,range:16—72 years) histologically

  14. Removing the age restrictions for rotavirus vaccination: a benefit-risk modeling analysis.

    Directory of Open Access Journals (Sweden)

    Manish M Patel

    Full Text Available BACKGROUND: To minimize potential risk of intussusception, the World Health Organization (WHO recommended in 2009 that rotavirus immunization should be initiated by age 15 weeks and completed before 32 weeks. These restrictions could adversely impact vaccination coverage and thereby its health impact, particularly in developing countries where delays in vaccination often occur. METHODS AND FINDINGS: We conducted a modeling study to estimate the number of rotavirus deaths prevented and the number of intussusception deaths caused by vaccination when administered on the restricted schedule versus an unrestricted schedule whereby rotavirus vaccine would be administered with DTP vaccine up to age 3 years. Countries were grouped on the basis of child mortality rates, using WHO data. Inputs were estimates of WHO rotavirus mortality by week of age from a recent study, intussusception mortality based on a literature review, predicted vaccination rates by week of age from USAID Demographic and Health Surveys, the United Nations Children's Fund (UNICEF Multiple Indicator Cluster Surveys (MICS, and WHO-UNICEF 2010 country-specific coverage estimates, and published estimates of vaccine efficacy and vaccine-associated intussusception risk. On the basis of the error estimates and distributions for model inputs, we conducted 2,000 simulations to obtain median estimates of deaths averted and caused as well as the uncertainty ranges, defined as the 5th-95th percentile, to provide an indication of the uncertainty in the estimates. We estimated that in low and low-middle income countries a restricted schedule would prevent 155,800 rotavirus deaths (5th-95th centiles, 83,300-217,700 while causing potentially 253 intussusception deaths (76-689. In contrast, vaccination without age restrictions would prevent 203,000 rotavirus deaths (102,000-281,500 while potentially causing 547 intussusception deaths (237-1,160. Thus, removing the age restrictions would avert an

  15. The Development and Evaluation of a Professional Development Model to Build Meaningful and Effective IEPs for Transition-Aged Students

    Science.gov (United States)

    Doren, Bonnie; Flannery, K. Brigid; Lombardi, Allison

    2012-01-01

    The purpose of the study was to examine the potential efficacy of a professional development training model targeting IEP case managers of transition-age students. A training model was developed and a pilot study conducted to understand the promise of the model to improve the development of critical components within the IEP document that support…

  16. The Changing Nature of Adult Education in the Age of Transnational Migration: Toward a Model of Recognitive Adult Education

    Science.gov (United States)

    Guo, Shibao

    2015-01-01

    This chapter examines the changing nature of adult education in the age of transnational migration and proposes recognitive adult education as an inclusive model that acknowledges and affirms cultural difference and diversity as positive and desirable assets.

  17. Modelling of intermediate-age stellar populations III Effects of dust-shells around AGB stars

    CERN Document Server

    Mouhcine, M

    2002-01-01

    In this paper,we present single stellar population models of intermediate age stellar populations where dust-enshrouded AGB stars are introduced. The formation of carbon stars is also accounted for, and is taken to be a function of both initial mass and metallicity. The effect of the dusty envelopes around AGB stars on the optical/near-infrared spectral energy distribution were introduced using semi-emipirical models where the mass-loss and the photospheric chemistry determine the spectral properties of a star along the AGB sequence. The spectral dichotomy between O-rich stars and C-rich stars is taken into account in the modelling. We have investigated the AGB sequence morphology in he near-infrared CMD as a function of time and metallicity. We show that this diaggram is characterized by three morphological features, occupied by optically bright O-rich stars, optically bright C-rich stars, and dust-enshrouded O-rich and C-rich stars respectively. Our models are able to reproduce the distribution of the three...

  18. The Use of Mouse Models for Understanding the Biology of Down Syndrome and Aging

    Directory of Open Access Journals (Sweden)

    Guido N. Vacano

    2012-01-01

    Full Text Available Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress in their production and analysis has been remarkable. Here, we describe various mouse models that have been used to study Down syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to human chromosome 21, mice in which individual genes have been introduced, or mice in which genes have been silenced by targeted mutagenesis. We selected a limited number of genes for which considerable evidence links them to aspects of Down syndrome, and about which much is known regarding their function. We focused on genes important for brain and cognitive function, and for the altered cancer spectrum seen in individuals with Down syndrome. We conclude with observations on the usefulness of mouse models and speculation on future directions.

  19. The use of mouse models for understanding the biology of down syndrome and aging.

    Science.gov (United States)

    Vacano, Guido N; Duval, Nathan; Patterson, David

    2012-01-01

    Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress in their production and analysis has been remarkable. Here, we describe various mouse models that have been used to study Down syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to human chromosome 21, mice in which individual genes have been introduced, or mice in which genes have been silenced by targeted mutagenesis. We selected a limited number of genes for which considerable evidence links them to aspects of Down syndrome, and about which much is known regarding their function. We focused on genes important for brain and cognitive function, and for the altered cancer spectrum seen in individuals with Down syndrome. We conclude with observations on the usefulness of mouse models and speculation on future directions.

  20. Modelling realistic horizontal branch morphologies and their impact on spectroscopic ages of unresolved stellar systems

    CERN Document Server

    Percival, Susan M

    2010-01-01

    The presence of an extended blue horizontal branch (HB) in a stellar population is known to affect the age inferred from spectral fitting to stellar population synthesis models. However, most population synthesis models still rely on theoretical isochrones which do not include realistic modelling of extended HBs. In this work, we create detailed models for a range of old simple stellar populations (SSPs), to create a variety of realistic HB morphologies, from extended red clumps, to extreme blue HBs. We achieve this by utilising stellar tracks from the BaSTI database and implementing a different mass loss prescription for each SSP created, resulting in different HB morphologies. We find that, for each metallicity, there is some HB morphology which maximises Hbeta, making an underlying 14Gyr population look ~5-6Gyr old for the low and intermediate metallicity cases, and as young as 2Gyr for a solar metallicity SSP. We explore whether there are any spectral indices capable of breaking the degeneracy between an ...

  1. Geologic constraints on kinematic models and age of formation of the Amerasia Basin of the Arctic

    Science.gov (United States)

    Miller, E. L.

    2015-12-01

    A wealth of new geologic and geophysical data now exist for the Amerasia Basin, but the details of its age and the nature/kinematics of events that resulted in its formation remain elusive. Basement rock ages, detrital zircon signatures of sedimentary rocks, and sediment dispersal systems have been used to show how parts of the southern margin(s) of the Amerasia Basin (Arctic Alaska-Chukotka, AAC) match their rifted margin counterparts on the Eurasia and Canada side of the Amerasia Basin. Thus we know the approximate finite translations needed to restore the paleogeography of the Arctic, but not the kinematics involved. Important features of the Amerasia Basin that need to be explained in a model for its opening are the age and extent of the high Arctic LIP, the linearity of the strip of continental crust represented by the Lomonosov Ridge, its right angle intersection with the Canadian Arctic margin, and the directional fault patterns mapped bathymetrically and seismically across the Alpha-Lomonosov Ridge and surrounding seafloor. Across AAC, post-Early Cretaceous oroclinal bends provide insight into strike-slip components of deformation involved in opening of the Amerasia Basin: The Chukchi syntax offsets the Brooks Range in a right-lateral sense from Wrangel Island along the Herald Arch; right-lateral motion of Arctic Alaska with respect to the Chukchi Borderland during opening of the Canada Basin; right-lateral shear in Chukotka during 100 Ma magmatism; the tight bend in the northern Verkhoyansk, result of Cretaceous right-lateral shear. The land-based relationships imply a post-Early Cretaceous, younger than Barremian (~130 Ma) age for onset of magmatism and extension related to rifting and formation of the Amerasia Basin. At least two stages of extension are documented, with older E-W extension characterizing the longitude of the New Siberian Islands to Pevek, Russian Arctic, (ca.125 Ma to 100 Ma), with younger N-S extension superimposed on this system (ca

  2. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    Science.gov (United States)

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  3. Intercomparison of radiocarbon bomb pulse and 210Pb age models. A study in a peat bog core from North Poland

    Science.gov (United States)

    Piotrowska, Natalia; De Vleeschouwer, François; Sikorski, Jarosław; Pawlyta, Jacek; Fagel, Nathalie; Le Roux, Gaël; Pazdur, Anna

    2010-04-01

    Radiocarbon and 210Pb were measured on the uppermost 40 cm of a Wardenaar peat core retrieved from a Baltic raised bog at Słowińskie Błota (Pomerania, North Poland). This site is the subject of ongoing multiproxy studies covering the last 1300 years. Radiocarbon age model was constructed on the basis of 14 AMS dates obtained on selected Sphagnum spp. fragments, with use of P_Sequence tool. We present here a comparison of this model with the age model obtained using CRS model classically applied to 210Pb measurements.

  4. Nonvibrating granular model for a glass-forming liquid: Equilibration and aging

    Science.gov (United States)

    Tapia-Ignacio, C.; Garcia-Serrano, J.; Donado, F.

    2016-12-01

    We studied experimentally a model of a glass-forming liquid on the basis of a nonvibrating magnetic granular system under an unsteady magnetic field. A sudden quenching was produced that drove the system from a liquid state to a different final state with lower temperature; the latter could be a liquid state or a solid state. We determined the mean-squared displacement in temporal windows to obtain the dynamic evolution of the system, and we determined the radial distribution function to obtain its structural characteristics. The results were analyzed using the intermediate scattering function and the effective potential between two particles. We observed that when quenching drives the system to a final state in the liquid phase far from the glass-transition temperature, equilibration occurs very quickly. When the final state has a temperature far below the glass-transition temperature, the system reaches its equilibrium state very quickly. In contrast, when the final state has an intermediate temperature but is below that corresponding to the glass transition, the system falls into a state that evolves slowly, presenting aging. The system evolves by an aging process toward more ordered states. However, after a waiting time, the dynamic behavior changes. It was observed that some particles get close enough to overpass the repulsive interactions and form small stable aggregates. In the effective potential curves, it was observed that the emergence of a second effective well due to the attraction quickly evolves and results in a deeper well than the initial effective well due to the repulsion. With the increase in time, more particles fall in the attractive well forming inhomogeneities, which produce a frustration in the aging process.

  5. Cardiological aging in SAM model: effect of chronic treatment with growth hormone.

    Science.gov (United States)

    Forman, K; Vara, E; García, C; Ariznavarreta, C; Escames, G; Tresguerres, J A F

    2010-06-01

    The purpose of this study was to investigate the effect of aging on different parameters related to inflammation, oxidative stress and apoptosis in hearts from two types of male mice models: senescence-accelerated mice (SAM-P8) and senescence-accelerated-resistant (SAM-R1), and the influence of chronic administration of Growth Hormone (GH) on old SAM-P8 mice. Forty male mice were used. Animals were divided into five experimental groups: two 10 month old untreated groups (SAM-P8/SAM-R1), two 2 month old young groups (SAM-P8/SAM-R1) and one 10 month old group (SAM-P8) treated with GH for 30 days. The expression of tumor necrosis factor-alpha, interleukin 1, interleukin 10, heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases, NFkB, Bad, Bax and Bcl-2 were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Results were submitted to a two way ANOVA statistical evaluation using the Statgraphics program. Inflammation, as well as, oxidative stress and apoptosis markers were increased in the heart of old SAM-P8 males, as compared to young controls and this situation was not observed in the old SAM-R1 mice. Exogenous GH administration reverted the effect of aging in the described parameters of old SAM-P8 mice. Our results suggest that inflammation, apoptosis and oxidative stress could play an important role in the observed cardiovascular alterations related to aging of SAM-P8 mice and that GH may play a potential protective effect on the cardiovascular system of these animals.

  6. Ultrastructural features of skeletal muscle in adult and aging Ts65Dn mice, a murine model of Down syndrome.

    Science.gov (United States)

    Cisterna, Barbara; Costanzo, Manuela; Scherini, Elda; Zancanaro, Carlo; Malatesta, Manuela

    2013-10-01

    Patients with Down syndrome (DS) suffer from muscle hypotonia and an altered motor coordination whose basic mechanisms are still largely unknown. Interestingly, they show muscle weakness like healthy aged subjects, suggesting possible similarity with sarcopenia: to test this hypothesis, the Ts65Dn mouse, a suitable animal model of DS, was employed. The fine structure of skeletal fibres of the quadriceps femoris muscle was analysed in adult (12 months) and aging (19 months) animals and their age-matched euploid controls by combining morphometry and immunocytochemistry at transmission electron microscopy. Results demonstrated structural alterations of mitochondria and myonuclei reminiscent of those observed in age-related sarcopenia, supporting the hypothesis that trisomy leads to an early aging of skeletal muscle consistent with the multi-systemic premature aging typical of DS.

  7. A holistic aging model for Li(NiMnCo)O2 based 18650 lithium-ion batteries

    Science.gov (United States)

    Schmalstieg, Johannes; Käbitz, Stefan; Ecker, Madeleine; Sauer, Dirk Uwe

    2014-07-01

    Knowledge on lithium-ion battery aging and lifetime estimation is a fundamental aspect for successful market introduction in high-priced goods like electric mobility. This paper illustrates the parameterization of a holistic aging model from accelerated aging tests. More than 60 cells of the same type are tested to analyze different impact factors. In calendar aging tests three temperatures and various SOC are applied to the batteries. For cycle aging tests especially different cycle depths and mean SOC are taken into account. Capacity loss and resistance increase are monitored as functions of time and charge throughput during the tests. From these data physical based functions are obtained, giving a mathematical description of aging. To calculate the stress factors like temperature or voltage, an impedance based electric-thermal model is coupled to the aging model. The model accepts power and current profiles as input, furthermore an ambient air temperature profile can be applied. Various drive cycles and battery management strategies can be tested and optimized using the lifetime prognosis of this tool. With the validation based on different realistic driving profiles and temperatures, a robust foundation is provided.

  8. A partial exponential lumped parameter model to evaluate groundwater age distributions and nitrate trends in long-screened wells

    Science.gov (United States)

    Jurgens, Bryant C.; Böhlke, J. K.; Kauffman, Leon J.; Belitz, Kenneth; Esser, Bradley K.

    2016-12-01

    A partial exponential lumped parameter model (PEM) was derived to determine age distributions and nitrate trends in long-screened production wells. The PEM can simulate age distributions for wells screened over any finite interval of an aquifer that has an exponential distribution of age with depth. The PEM has 3 parameters - the ratio of saturated thickness to the top and bottom of the screen and mean age, but these can be reduced to 1 parameter (mean age) by using well construction information and estimates of the saturated thickness. The PEM was tested with data from 30 production wells in a heterogeneous alluvial fan aquifer in California, USA. Well construction data were used to guide parameterization of a PEM for each well and mean age was calibrated to measured environmental tracer data (3H, 3He, CFC-113, and 14C). Results were compared to age distributions generated for individual wells using advective particle tracking models (PTMs). Age distributions from PTMs were more complex than PEM distributions, but PEMs provided better fits to tracer data, partly because the PTMs did not simulate 14C accurately in wells that captured varying amounts of old groundwater recharged at lower rates prior to groundwater development and irrigation. Nitrate trends were simulated independently of the calibration process and the PEM provided good fits for at least 11 of 24 wells. This work shows that the PEM, and lumped parameter models (LPMs) in general, can often identify critical features of the age distributions in wells that are needed to explain observed tracer data and nonpoint source contaminant trends, even in systems where aquifer heterogeneity and water-use complicate distributions of age. While accurate PTMs are preferable for understanding and predicting aquifer-scale responses to water use and contaminant transport, LPMs can be sensitive to local conditions near individual wells that may be inaccurately represented or missing in an aquifer-scale flow model.

  9. A partial exponential lumped parameter model to evaluate groundwater age distributions and nitrate trends in long-screened wells

    Science.gov (United States)

    Jurgens, Bryant; Bohlke, John Karl; Kauffman, Leon J.; Belitz, Kenneth; Esser, Bradley K.

    2016-01-01

    A partial exponential lumped parameter model (PEM) was derived to determine age distributions and nitrate trends in long-screened production wells. The PEM can simulate age distributions for wells screened over any finite interval of an aquifer that has an exponential distribution of age with depth. The PEM has 3 parameters – the ratio of saturated thickness to the top and bottom of the screen and mean age, but these can be reduced to 1 parameter (mean age) by using well construction information and estimates of the saturated thickness. The PEM was tested with data from 30 production wells in a heterogeneous alluvial fan aquifer in California, USA. Well construction data were used to guide parameterization of a PEM for each well and mean age was calibrated to measured environmental tracer data (3H, 3He, CFC-113, and 14C). Results were compared to age distributions generated for individual wells using advective particle tracking models (PTMs). Age distributions from PTMs were more complex than PEM distributions, but PEMs provided better fits to tracer data, partly because the PTMs did not simulate 14C accurately in wells that captured varying amounts of old groundwater recharged at lower rates prior to groundwater development and irrigation. Nitrate trends were simulated independently of the calibration process and the PEM provided good fits for at least 11 of 24 wells. This work shows that the PEM, and lumped parameter models (LPMs) in general, can often identify critical features of the age distributions in wells that are needed to explain observed tracer data and nonpoint source contaminant trends, even in systems where aquifer heterogeneity and water-use complicate distributions of age. While accurate PTMs are preferable for understanding and predicting aquifer-scale responses to water use and contaminant transport, LPMs can be sensitive to local conditions near individual wells that may be inaccurately represented or missing in an aquifer-scale flow model.

  10. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    Directory of Open Access Journals (Sweden)

    Chatchada Sutalangka

    2013-01-01

    Full Text Available To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s are still required.

  11. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    Science.gov (United States)

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

  12. A clinical practice model for treatment of college-aged incest survivors.

    Science.gov (United States)

    Barney, E E

    1990-05-01

    Adult incest survivors frequently exhibit signs and symptoms of posttraumatic stress disorder. Many clinicians have geared their group treatment of incest survivors to address these manifestations. Given the nature of the sexual abuse, the early developmental periods in which some trauma occurs, the past and current relationship between the victim and the perpetrator, and the dynamics inherent in this violation and betrayal of trust, love, and power within the family unit, additional clinical concerns and safeguards must be considered. In addition, the struggles of college-aged incest survivors to come to terms with their history of sexual abuse often mirror the developmental tasks faced by their peers--autonomy, intimacy, sexuality, and formation of personal values and ethics. To focus solely on the incest without also considering these developmental issues may solidify a gridlock between inadequate resolution of the developmental issues and the continued victimization of the student incest survivor. The author discusses a time-limited group treatment for college-aged incest survivors that uses a modified posttraumatic stress disorder model as a conceptual framework and addresses both sets of concerns.

  13. Longitudinal examination of the exercise and self-esteem model in middle-aged women.

    Science.gov (United States)

    Elavsky, Steriani

    2010-12-01

    This 2-year prospective study examined the exercise and self-esteem model in middle-aged women (N = 143) previously enrolled in a randomized controlled exercise trial. Across the 2-year period, increases in physical activity (PA) and self-efficacy and reductions in body mass index (BMI) were associated with improved subdomain self-perceptions relative to physical condition, and reductions in BMI were associated with improved subdomain self-perceptions relative to physical condition and body attractiveness. The effects of PA, self-efficacy, and BMI on changes in physical self-worth and global self-esteem were mediated by changes in self-perceptions relative to physical condition and body attractiveness. The results of this longitudinal analysis support the hierarchical and multidimensional structure of self-esteem and indicate that middle-aged women can enhance how they perceive their condition and body attractiveness by continued participation in physical activity, increasing their self-efficacy, and maintaining healthy BMI levels.

  14. Immune responses accelerate ageing: proof-of-principle in an insect model.

    Directory of Open Access Journals (Sweden)

    E Rhiannon Pursall

    Full Text Available The pathology of many of the world's most important infectious diseases is caused by the immune response. Additionally age-related disease is often attributed to inflammatory responses. Consequently a reduction in infections and hence inflammation early in life has been hypothesized to explain the rise in lifespan in industrialized societies. Here we demonstrate experimentally for the first time that eliciting an immune response early in life accelerates ageing. We use the beetle Tenebrio molitor as an inflammation model. We provide a proof of principle for the effects of early infection on morbidity late in life and demonstrate a long-lasting cost of immunopathology. Along with presenting a proof-of-principle study, we discuss a mechanism for the apparently counter-adaptive persistence of immunopathology in natural populations. If immunopathology from early immune response only becomes costly later in life, natural selection on reducing self-harm would be relaxed, which could explain the presence of immune self-harm in nature.

  15. Deposition times in the northeastern United States during the Holocene: establishing valid priors for Bayesian age models

    Science.gov (United States)

    Goring, S.; Williams, J. W.; Blois, J. L.; Jackson, S. T.; Paciorek, C. J.; Booth, R. K.; Marlon, J. R.; Blaauw, M.; Christen, J. A.

    2012-08-01

    Age-depth relationships in sedimentary archives such as lakes, wetlands and bogs are non-linear with irregular probability distributions associated with calibrated radiocarbon dates. Bayesian approaches are thus well-suited to understanding relationships between age and depth for use in paleoecological studies. Bayesian models for the accumulation of sediment and organic matter within basins combine dated material from one or more records with prior information about the behavior of deposition times (yr/cm) based on expert knowledge. Well-informed priors are essential to good modeling of the age-depth relationship, but are particularly important in cases where data may be sparse (e.g., few radiocarbon dates), or unclear (e.g., age-reversals, coincident dates, age offsets, outliers and dates within a radiocarbon plateau). Here we assessed Holocene deposition times using 204 age-depth models obtained from the Neotoma Paleoecology Database (www.neotomadb.org) for both lacustrine and palustrine environments across the northeastern United States. These age-depth models were augmented using biostratigraphic events identifiable within pollen records from the northeastern United States during the Holocene and late-Pleistocene. Deposition times are significantly related to depositional environment (palustrine and lacustrine), sediment age, and sediment depth. Spatial variables had non-significant relationships with deposition time when site effects were considered. The best-fit model was a generalized additive mixed model that relates deposition time to age, stratified by depositional environment with site as a random factor. The best-fit model accounts for 63.3% of the total deviance in deposition times. The strongly increasing accumulation rates of the last 500-1000 years indicate that gamma distributions describing lacustrine deposition times (α = 1.08, β = 18.28) and palustrine deposition times (α = 1.23, β = 22.32) for the entire Holocene may be insufficient for

  16. Channel selection in e-commerce age: A strategic analysis of co-op advertising models

    Directory of Open Access Journals (Sweden)

    Yongmei Liu

    2013-03-01

    , such as service and price. We can do some researches from the point of these factors. Third, how demand uncertainty affects the channel selection and co-op advertising strategy is another interesting research item.Practical implications: The manufacturer and the retailer know that the impact of co-op adverting on the demands of traditional channel and direct channel, both would like to choose reasonable strategies to improve the channel coordination. Therefore, it would be best if business managers conduct market survey before they start their co-op advertising campaign.Originality/value: Two new co-op advertising models in E-commerce age are developed, and the impact of product web-fit on these optimal strategies are analyzed and illustrate by some numeral examples. In addition, optimal channel structure in E-commerce age are selected for manufacturer and the retailer.

  17. Application Server Aging Model and Multi-Level Rejuvenation Strategy Using Semi-Markov Process

    Institute of Scientific and Technical Information of China (English)

    ZHAO Tianhai; QI Yong; SHEN Junyi; HOU Di; ZHENG Xiaomei; LIU Liang

    2006-01-01

    Aiming at the characteristic of the dependency between the application components and the application server platform, a rejuvenation strategy with two different levels of rejuvenation granularities is put forward in this paper including the application component rejuvenation and the application server system rejuvenation. The availability and maintenance cost functions are obtained by means of establishing the application server aging model and the boundary condition of the optimal rejuvenation time is analyzed. Theory analysis indicates that the two-level rejuvenation strategy is superior to the traditional single level one. Finally, evaluation experiments are carried out and numerical result shows that compared with the traditional rejuvenation policy, the rejuvenation strategy proposed in this paper can further increase availability of the application server and reduce maintenance cost.

  18. Modelling the chemically aged and mixed aerosols over the eastern central Atlantic Ocean – potential impacts

    Directory of Open Access Journals (Sweden)

    M. Astitha

    2010-07-01

    Full Text Available Detailed information on the chemical and physical properties of aerosols is important for assessing their role in air quality and climate. This work explores the origin and fate of continental aerosols transported over the Central Atlantic Ocean, in terms of chemical composition, number and size distribution, using chemistry-transport models, satellite data and in situ measurements. We focus on August 2005, a period with intense hurricane and tropical storm activity over the Atlantic Ocean. A mixture of anthropogenic (sulphates, nitrates, natural (desert dust, sea salt and chemically aged (sulphate and nitrate on dust aerosols is found entering the hurricane genesis region, most likely interacting with clouds in the area. Results from our modelling study suggest rather small amounts of accumulation mode desert dust, sea salt and chemically aged dust aerosols in this Atlantic Ocean region. Aerosols of smaller size (Aitken mode are more abundant in the area and in some occasions sulphates of anthropogenic origin and desert dust are of the same magnitude in terms of number concentrations. Typical aerosol number concentrations are derived for the vertical layers near shallow cloud formation regimes, indicating that the aerosol number concentration can reach several thousand particles per cubic centimetre. The vertical distribution of the aerosols shows that the desert dust particles are often transported near the top of the marine cloud layer as they enter into the region where deep convection is initiated. The anthropogenic sulphate aerosol can be transported within a thick layer and enter the cloud deck through multiple ways (from the top, the base of the cloud, and by entrainment. The sodium (sea salt related aerosol is mostly found below the cloud base. The results of this work may provide insights relevant for studies that consider aerosol influences on cloud processes and storm development in the Central Atlantic region.

  19. Modelling the chemically aged and mixed aerosols over the eastern central Atlantic Ocean - potential impacts

    Science.gov (United States)

    Astitha, M.; Kallos, G.; Spyrou, C.; O'Hirok, W.; Lelieveld, J.; Denier van der Gon, H. A. C.

    2010-07-01

    Detailed information on the chemical and physical properties of aerosols is important for assessing their role in air quality and climate. This work explores the origin and fate of continental aerosols transported over the Central Atlantic Ocean, in terms of chemical composition, number and size distribution, using chemistry-transport models, satellite data and in situ measurements. We focus on August 2005, a period with intense hurricane and tropical storm activity over the Atlantic Ocean. A mixture of anthropogenic (sulphates, nitrates), natural (desert dust, sea salt) and chemically aged (sulphate and nitrate on dust) aerosols is found entering the hurricane genesis region, most likely interacting with clouds in the area. Results from our modelling study suggest rather small amounts of accumulation mode desert dust, sea salt and chemically aged dust aerosols in this Atlantic Ocean region. Aerosols of smaller size (Aitken mode) are more abundant in the area and in some occasions sulphates of anthropogenic origin and desert dust are of the same magnitude in terms of number concentrations. Typical aerosol number concentrations are derived for the vertical layers near shallow cloud formation regimes, indicating that the aerosol number concentration can reach several thousand particles per cubic centimetre. The vertical distribution of the aerosols shows that the desert dust particles are often transported near the top of the marine cloud layer as they enter into the region where deep convection is initiated. The anthropogenic sulphate aerosol can be transported within a thick layer and enter the cloud deck through multiple ways (from the top, the base of the cloud, and by entrainment). The sodium (sea salt related) aerosol is mostly found below the cloud base. The results of this work may provide insights relevant for studies that consider aerosol influences on cloud processes and storm development in the Central Atlantic region.

  20. Uranium isotopes and dissolved organic carbon in loess permafrost: Modeling the age of ancient ice

    Science.gov (United States)

    Ewing, Stephanie A.; Paces, James B.; O'Donnell, J.A.; Jorgenson, M.T.; Kanevskiy, M.Z.; Aiken, George R.; Shur, Y.; Harden, Jennifer W.; Striegl, Robert G.

    2015-01-01

    The residence time of ice in permafrost is an indicator of past climate history, and of the resilience and vulnerability of high-latitude ecosystems to global change. Development of geochemical indicators of ground-ice residence times in permafrost will advance understanding of the circumstances and evidence of permafrost formation, preservation, and thaw in response to climate warming and other disturbance. We used uranium isotopes to evaluate the residence time of segregated ground ice from ice-rich loess permafrost cores in central Alaska. Activity ratios of 234U vs. 238U (234U/238U) in water from thawed core sections ranged between 1.163 and 1.904 due to contact of ice and associated liquid water with mineral surfaces over time. Measured (234U/238U) values in ground ice showed an overall increase with depth in a series of five neighboring cores up to 21 m deep. This is consistent with increasing residence time of ice with depth as a result of accumulation of loess over time, as well as characteristic ice morphologies, high segregated ice content, and wedge ice, all of which support an interpretation of syngenetic permafrost formation associated with loess deposition. At the same time, stratigraphic evidence indicates some past sediment redistribution and possibly shallow thaw among cores, with local mixing of aged thaw waters. Using measures of surface area and a leaching experiment to determine U distribution, a geometric model of (234U/238U) evolution suggests mean ages of up to ∼200 ky BP in the deepest core, with estimated uncertainties of up to an order of magnitude. Evidence of secondary coatings on loess grains with elevated (234U/238U) values and U concentrations suggests that refinement of the geometric model to account for weathering processes is needed to reduce uncertainty. We suggest that in this area of deep ice-rich loess permafrost, ice bodies have been preserved from the last glacial period (10–100 ky BP), despite subsequent

  1. Application of third molar development and eruption models in estimating dental age in Malay sub-adults.

    Science.gov (United States)

    Mohd Yusof, Mohd Yusmiaidil Putera; Cauwels, Rita; Deschepper, Ellen; Martens, Luc

    2015-08-01

    The third molar development (TMD) has been widely utilized as one of the radiographic method for dental age estimation. By using the same radiograph of the same individual, third molar eruption (TME) information can be incorporated to the TMD regression model. This study aims to evaluate the performance of dental age estimation in individual method models and the combined model (TMD and TME) based on the classic regressions of multiple linear and principal component analysis. A sample of 705 digital panoramic radiographs of Malay sub-adults aged between 14.1 and 23.8 years was collected. The techniques described by Gleiser and Hunt (modified by Kohler) and Olze were employed to stage the TMD and TME, respectively. The data was divided to develop three respective models based on the two regressions of multiple linear and principal component analysis. The trained models were then validated on the test sample and the accuracy of age prediction was compared between each model. The coefficient of determination (R²) and root mean square error (RMSE) were calculated. In both genders, adjusted R² yielded an increment in the linear regressions of combined model as compared to the individual models. The overall decrease in RMSE was detected in combined model as compared to TMD (0.03-0.06) and TME (0.2-0.8). In principal component regression, low value of adjusted R(2) and high RMSE except in male were exhibited in combined model. Dental age estimation is better predicted using combined model in multiple linear regression models.

  2. Modelling of leaching and geochemical processes in an aged MSWIBA subbase layer

    Energy Technology Data Exchange (ETDEWEB)

    Bendz, David; Suer, Pascal; Sloot, Hans van der; Kosson, David; Flyhammar, Peter

    2009-07-15

    In a previous project, the accumulated effects of leaching and aging in a subbase layer of bottom ash in a test road were investigated. The test road were constructed in 1987 in Linkoeping, Sweden, and was in use until the start of the Vaendoera Q4-241 study in September 2003. The overall objective of the present study is to bring the evaluation of the previous project (Q4-241) further by taking advantage of the existing data, perform complementary laboratory experiments on four composite samples reflecting different degree of exposure to atmosphere and leaching. The specific objectives were to investigate: (i) what processes and mineral phases that govern leaching of macro- and trace elements and DOC in the bottom ash after 16 years (1987- 2003) of aging under field conditions. (ii) how the hydrologic conditions, infiltration of water and leachate production has evolved with time. The following tests were performed on the composite samples: pH-stat test, column test, Fe/Al oxide extraction and TOC fractioning. Geochemical and hydrological modelling where performed with LeachXS/Orchestra and Hydrus 2-D. Daily precipitation data from the Swedish Meteorological and Hydrological Institute (SMHI) from the Malmslaett (Linkoeping) measurement station was used in the hydrological modelling of January 1988 to the 1st of september 2003. The hydraulic modeling results show that the bottom ash subbase layer endure seasonal wet and dry cycles. The results confirm that, depending on the boundary conditions along the shoulders the capillary potential may drive moisture either in or out of the road body. The water retention parameters for bottom ash were crucial in the hydraulic modeling and the capillary forces in bottom ash were found to be significant with a water retention curve close to silt. This explains the observed depletion of easily soluble salts in the test road. The results showed that the accumulated LS ratio for the bottom ash subbase layer reached about LS:10 in

  3. Application of artificial neural networks for modelling correlations in age hardenable aluminium alloys

    Directory of Open Access Journals (Sweden)

    F. Musharavati

    2010-07-01

    Full Text Available Purpose: This paper discusses some of the preliminary results of an ongoing research on the applications of artificial neural networks (ANNs in modelling, predicting and simulating correlations between mechanical properties of age hardenable aluminium alloys as a function of alloy composition.Design/methodology/approach: Appropriate combinations of inputs and outputs were selected for neural network modelling. Multilayer feedforward networks were created and trained using datasets from public literature. Influences of alloying elements, alloy composition and processing parameters on mechanical properties of aluminium alloys were predicted and simulated using ANNs models.Two sample t-tests were used to analyze the prediction accuracy of the trained ANNs.Findings: Good performances of the neural network models were achieved. The models were able to predict mechanical properties within acceptable margins of error and were able to provide relevant simulated data for correlating alloy composition and processing parameters with mechanical properties. Therefore, ANNs models are convenient and powerful tools that can provide useful information which can be used to identify desired properties in new aluminium alloys for practical applications in new and/or improved aluminium products.Research limitations/implications: Few public data bases are available for modelling properties. Minor contradictions on the experimental values of properties and alloy compositions were also observed. Future work will include further development of simulated data into property charts.Practical implications: Correlations between mechanical properties and alloy compositions can help in identifying a suitable alloy for a new or improved aluminum product application. In addition, availability of simulated structure-process-property data or charts assists in reducing the time and costs of trial and error experimental approaches by providing near-optimal values that can be used

  4. A model for damage load and its implications for the evolution of bacterial aging.

    Directory of Open Access Journals (Sweden)

    Lin Chao

    2010-08-01

    Full Text Available Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry.

  5. Prediction of aged red wine aroma properties from aroma chemical composition. Partial least squares regression models.

    Science.gov (United States)

    Aznar, Margarita; López, Ricardo; Cacho, Juan; Ferreira, Vicente

    2003-04-23

    Partial least squares regression (PLSR) models able to predict some of the wine aroma nuances from its chemical composition have been developed. The aromatic sensory characteristics of 57 Spanish aged red wines were determined by 51 experts from the wine industry. The individual descriptions given by the experts were recorded, and the frequency with which a sensory term was used to define a given wine was taken as a measurement of its intensity. The aromatic chemical composition of the wines was determined by already published gas chromatography (GC)-flame ionization detector and GC-mass spectrometry methods. In the whole, 69 odorants were analyzed. Both matrixes, the sensory and chemical data, were simplified by grouping and rearranging correlated sensory terms or chemical compounds and by the exclusion of secondary aroma terms or of weak aroma chemicals. Finally, models were developed for 18 sensory terms and 27 chemicals or groups of chemicals. Satisfactory models, explaining more than 45% of the original variance, could be found for nine of the most important sensory terms (wood-vanillin-cinnamon, animal-leather-phenolic, toasted-coffee, old wood-reduction, vegetal-pepper, raisin-flowery, sweet-candy-cacao, fruity, and berry fruit). For this set of terms, the correlation coefficients between the measured and predicted Y (determined by cross-validation) ranged from 0.62 to 0.81. Models confirmed the existence of complex multivariate relationships between chemicals and odors. In general, pleasant descriptors were positively correlated to chemicals with pleasant aroma, such as vanillin, beta damascenone, or (E)-beta-methyl-gamma-octalactone, and negatively correlated to compounds showing less favorable odor properties, such as 4-ethyl and vinyl phenols, 3-(methylthio)-1-propanol, or phenylacetaldehyde.

  6. Variance components models for physical activity with age as modifier: a comparative twin study in seven countries

    DEFF Research Database (Denmark)

    Vink, Jacqueline M; Boomsma, Dorret I; Medland, Sarah E;

    2011-01-01

    Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self-reported ......Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self......-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease...... into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts....

  7. Existence and uniqueness of endemic states for the age-structured S-I-R epidemic model.

    Science.gov (United States)

    Cha, Y; Iannelli, M; Milner, F A

    1998-06-15

    The existence and uniqueness of positive steady states for the age structured S-I-R epidemic model with intercohort transmission is considered. Threshold results for the existence of endemic states are established for most cases. Uniqueness is shown in each case. Threshold used are explicitly computable in terms of demographic and epidemiological parameters of the model.

  8. A note on the global properties of an age-structured viral dynamic model with multiple target cell populations.

    Science.gov (United States)

    Wang, Shaoli; Wu, Jianhong; Rong, Libin

    2017-06-01

    Some viruses can infect different classes of cells. The age of infection can affect the dynamics of infected cells and viral production. Here we develop a viral dynamic model with the age of infection and multiple target cell populations. Using the methods of semigroup and Lyapunov function, we study the global asymptotic property of the steady states of the model. The results show that when the basic reproductive number falls below 1, the infection is predicted to die out. When the basic reproductive number exceeds 1, there exists a unique infected steady state which is globally asymptotically stable. The model can be extended to study virus dynamics with multiple compartments or coinfection by multiple types of viruses. We also show that under some scenarios the age-structured model can be reduced to an ordinary differential equation system with or without time delays.

  9. Effects of Eurycoma longifolia on Testosterone Level and Bone Structure in an Aged Orchidectomised Rat Model

    Directory of Open Access Journals (Sweden)

    Abdul Shukor Tajul Ariff

    2012-01-01

    Full Text Available Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.

  10. Animal models for small for gestational age and fetal programming of adult disease.

    Science.gov (United States)

    Vuguin, Patricia M

    2007-01-01

    Fetal growth retardation is a fetal adaptation in response to inadequate supply of oxygen and/or nutrients. Animal models of intrauterine growth retardation are an invaluable tool to question the genetic, molecular and cellular events that determine fetal growth and development. Rodent and non-litter bearing animals are mammalian system with similar embryology,anatomy and physiology to humans. Utilization of these systems has led to a greater understanding of the pathophysiology and consequences of intrauterine growth retardation. These observations are comparable to that observed in humans born small for gestational age, and are of interest because of the known association between poor fetal growth and development of adult disease. All the experimental manipulations described here have altered a number of metabolic and physiological variables, but the pattern of alterations seems to vary with the procedure and species employed. This review describes animal models for intrauterine growth retardation and assesses their potentials and limitations at aiming to improve strategies for the prevention of adult disease.

  11. Pattern, growth, and aging in aggregation kinetics of a Vicsek-like active matter model

    Science.gov (United States)

    Das, Subir K.

    2017-01-01

    Via molecular dynamics simulations, we study kinetics in a Vicsek-like phase-separating active matter model. Quantitative results, for isotropic bicontinuous pattern, are presented on the structure, growth, and aging. These are obtained via the two-point equal-time density-density correlation function, the average domain length, and the two-time density autocorrelation function. Both the correlation functions exhibit basic scaling properties, implying self-similarity in the pattern dynamics, for which the average domain size exhibits a power-law growth in time. The equal-time correlation has a short distance behavior that provides reasonable agreement between the corresponding structure factor tail and the Porod law. The autocorrelation decay is a power-law in the average domain size. Apart from these basic similarities, the overall quantitative behavior of the above-mentioned observables is found to be vastly different from those of the corresponding passive limit of the model which also undergoes phase separation. The functional forms of these have been quantified. An exceptionally rapid growth in the active system occurs due to fast coherent motion of the particles, mean-squared-displacements of which exhibit multiple scaling regimes, including a long time ballistic one.

  12. Lithium prevents parkinsonian behavioral and striatal phenotypes in an aged parkin mutant transgenic mouse model.

    Science.gov (United States)

    Lieu, Christopher A; Dewey, Colleen M; Chinta, Shankar J; Rane, Anand; Rajagopalan, Subramanian; Batir, Sean; Kim, Yong-Hwan; Andersen, Julie K

    2014-12-03

    Lithium has long been used as a treatment for the psychiatric disease bipolar disorder. However, previous studies suggest that lithium provides neuroprotective effects in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease. The exact mechanism by which lithium exerts these effects still remains unclear. In the present study, we evaluated the effects of low-dose lithium treatment in an aged mouse model expressing a parkin mutation within dopaminergic neurons. We found that low-dose lithium treatment prevented motor impairment as demonstrated by the open field test, pole test, and rearing behavior. Furthermore, lithium prevented dopaminergic striatal degeneration in parkin animals. We also found that parkin-induced striatal astrogliosis and microglial activation were prevented by lithium treatment. Our results further corroborate the use of this parkin mutant transgenic mouse line as a model for PD for testing novel therapeutics. The findings of the present study also provide further validation that lithium could be re-purposed as a therapy for PD and suggest that anti-inflammatory effects may contribute to its neuroprotective mechanisms.

  13. Geological Characteristics and Model Ages of Marius Hills on the Moon

    Institute of Scientific and Technical Information of China (English)

    Jun Huang; Long Xiao; Xinxing He; Le Qiao; Jiannan Zhao; Hui Li

    2011-01-01

    Marius Hills is a volcanic plateau on the nearside of the Moon.It is of great interest for its high concentration of volcanic features,including domes,cones,ridges,and rilles.However,the morphological and chronological characteristics of this plateau were not well studied due to the low resolution of early mission data.This study describes the detailed morphology of the volcanic features using the latest high spatial resolution images of the Terrain Camera (TC) onboard Selene-1 (10 m/pix)and Narrow Angle Camera (NAC) onboard the Lunar Reconnaissance Orbiter (LRO) (0.5 m/pix).We report here some new structures such as skylights and remnants of lava tubes.We have divided spectrally homogenous areas with Clementine UVVIS data and did crater size frequency distribution (CSFD) measurements with Lunar Orbiter (LO) IV and TC images in every spectral unit.We first report absolute model ages of 1.10 Ga for Marius basalt 1,1.49 Ga for Flamsteed basalt,and 1.46 Ga for Schiaparelli Basalt.In addition,we have identified several younger lava events:they are Marius basalt 2 (814 Ma),medium to low titanium basalt (949 Ma),and undifferentiated medium titanium basalt (687 Ma).Finally,we propose a mantle plume scenario for the formation of Marius Hills,which could solve the inconsistency of previous models.

  14. Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Cemil, Berker; Gokce, Emre Cemal; Kahveci, Ramazan; Gokce, Aysun; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Erdogan, Bulent; Kosem, Bahadir

    2016-06-01

    Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury.

  15. A review of successful aging models: Proposing proactive coping as an important additional strategy

    NARCIS (Netherlands)

    Ouwehand, C.; Ridder, D.T.D. de; Bensing, J.

    2007-01-01

    Successful aging is an important concept, and one that has been the subject of much research. During the last 15 years, the emphasis of this research has shifted from formulating criteria for successful aging to describing the processes involved in successful aging. The main purpose of the present a

  16. A review of successful aging models: proposing proactive coping as an important additional strategy.

    NARCIS (Netherlands)

    Ouwehand, C.; Ridder, D.T.D. de; Bensing, J.M.

    2007-01-01

    Successful aging is an important concept, and one that has been the subject of much research. During the last 15 years, the emphasis of this research has shifted from formulating criteria for successful aging to describing the processes involved in successful aging. The main purpose of the present a

  17. Priming of microglia in a DNA-repair deficient model of accelerated aging

    NARCIS (Netherlands)

    Raj, Divya D. A.; Jaarsma, Dick; Holtman, Inge R.; Olah, Marta; Ferreira, Filipa M.; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M.; de Waard, Monique C.; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L.; Laman, Jon D.; de Haan, Gerald; Biber, Knut P. H.; Hoeijmakers, Jan H. J.; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    2014-01-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microgli

  18. Measurement and modeling of rainfall interception by two differently aged secondary forests in upland eastern Madagascar

    Science.gov (United States)

    Prasad Ghimire, Chandra; Adrian Bruijnzeel, L.; Lubczynski, Maciek W.; Ravelona, Maafaka; Zwartendijk, Bob W.; van Meerveld, H. J. (Ilja)

    2017-02-01

    Secondary forests occupy a larger area than old-growth rain forests in many tropical regions but their hydrological functioning is still poorly understood. In particular, little is known about the various components of evapotranspiration in these possibly vigorously regenerating forests. This paper reports on a comparison of measured and modeled canopy interception losses (I) from a semi-mature (ca. 20 years) and a young (5-7 years) secondary forest in the lower montane rain forest zone of eastern Madagascar. Measurements of gross rainfall (P), throughfall (Tf), and stemflow (Sf) were made in both forests for one year (October 2014-September 2015) and the revised analytical model of Gash et al. (1995) was tested for the first time in a tropical secondary forest setting. Overall measured Tf, Sf and derived I in the semi-mature forest were 71.0%, 1.7% and 27.3% of incident P, respectively. Corresponding values for the young forest were 75.8%, 6.2% and 18.0%. The high Sf for the young forest reflects the strongly upward thrusting habit of the branches of the dominant species (Psiadia altissima), which favours funneling of P. The value of I for the semi-mature forest is similar to values reported for old-growth tropical lower montane rain forests elsewhere but I for the younger forest is higher than reported for similarly aged tropical lowland forests. These findings can be explained largely by the prevailing low rainfall intensities and the frequent occurrence of small rainfall events. The revised analytical model was able to reproduce measured cumulative I at the two sites accurately and succeeded in capturing the variability in I associated with the seasonal variability in rainfall intensity, provided that Tf-based values for the average wet-canopy evaporation rates were used instead of values derived with the Penman-Monteith equation.

  19. AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats.

    Science.gov (United States)

    Yang, Shengzu; Litchfield, John E; Baynes, John W

    2003-04-01

    Advanced glycation end products (AGE), formed by nonenzymatic Maillard reactions between carbohydrate and protein, contribute to the increase in chemical modification and crosslinking of tissue proteins with age. Acceleration of AGE formation in collagen during hyperglycemia, with resultant effects on vascular elasticity and basement membrane permeability, is implicated in the pathogenesis of diabetic complications. AGE-breakers, such as N-phenacylthiazolium (PTB) and N-phenacyl-4,5-dimethylthiazolium (PMT) halides, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in aging and diabetes. We have confirmed that these compounds, as well as the AGE-inhibitor pyridoxamine (PM), cleave the model AGE crosslink, phenylpropanedione, and have studied the effects of these compounds in reversing the increased crosslinking of skin and tail collagen isolated from diabetic rats. Crosslinking of skin collagen, measured as the half-time for solubilization of collagen by pepsin in 0.5M acetic acid, was increased approximately 5-fold in diabetic, compared to nondiabetic rats. Crosslinking of tail tendon collagen, measured as insolubility in 0.05 N acetic acid, was increased approximately 10-fold. Collagen preparations were incubated in the presence or absence of AGE-breakers or PM in phosphate buffer, pH 7.4, for 24h at 37 degrees C. These treatments did not decrease the half-time for solubilization of diabetic skin collagen by pepsin or increase the acid solubility of diabetic tail tendon collagen. We conclude that, although AGE-breakers and PM cleave model crosslinks, they do not significantly cleave AGE crosslinks formed in vivo in skin collagen of diabetic rats.

  20. Existence, multiplicity and stability of endemic states for an age-structured S-I epidemic model.

    Science.gov (United States)

    Breda, D; Visetti, D

    2012-01-01

    We study an S-I type epidemic model in an age-structured population, with mortality due to the disease. A threshold quantity is found that controls the stability of the disease-free equilibrium and guarantees the existence of an endemic equilibrium. We obtain conditions on the age-dependence of the susceptibility to infection that imply the uniqueness of the endemic equilibrium. An example with two endemic equilibria is shown. Finally, we analyse numerically how the stability of the endemic equilibrium is affected by the extra-mortality and by the possible periodicities induced by the demographic age-structure.

  1. Age-related differences of neutrophil activation in a skeletal muscle ischemia-reperfusion model.

    Science.gov (United States)

    Mowlavi, Arian; Reynolds, Christopher; Neumeister, Michael W; Wilhelmi, Bradon J; Song, Yao-Hua; Naffziger, Ryan; Glatz, Frank R; Russell, Robert C

    2003-04-01

    Free tissue transfers and replantation of amputated limbs are better tolerated by young adolescents than mature adults. The authors hypothesized that this observation may be, in part, because of an attenuated ischemia-reperfusion (IR) injury in younger patients. Because neutrophils have been identified as a critical cell line responsible for IR injury, the authors investigated the effects of animal age on the degree of neutrophil activation in a rat model. Activation was evaluated by monitoring expression of integrin surface markers (mean fluorescence intensity [MFI] of CD11b) and oxidative burst potential (MFI of dihydrorhodamine [DHR] oxidation) by flow cytometry in neutrophils analyzed after 4 hours of ischemia and 1, 4, and 16 hours of reperfusion in a gracilis muscle flap model in mature adult and young adolescent rats. Neutrophil activation was also evaluated in control sham-operated animals, which underwent elevation of gracilis muscle flaps without exposure to an ischemic insult. Muscle edema, determined by wet-to-dry muscle weight ratio, and muscle viability, determined by nitro blue tetrazolium (NBT) staining, were completed for gracilis muscles exposed to ischemia after 24 hours of reperfusion for each of the groups. Integrin expression, assessed by MFI of CD11b, was increased significantly in ischemic muscles of mature adult rats at 4 hours of reperfusion (71.10+/-3.53 MFI vs. 54.88+/-12.73 MFI, p=0.025). Neutrophil oxidative potential, assessed by MFI of DHR oxidation, was increased significantly in ischemic muscles of mature adult rats compared with young adolescent rats at 1 hour of reperfusion (78.10+/-9.53 MFI vs. 51.78+/-16.91 MFI, p=0.035) and 4 hours of reperfusion (83.69+/-15.29 MFI vs. 46.55+/-8.09 MFI, p=0.005). Increased edema formation was observed in the ischemic muscles of mature adult rats when compared with young adolescent rats (1.25+/-0.04 vs. 1.12+/-0.05, p=0.031) after 24 hours of reperfusion. A trend toward decreased muscle

  2. Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous

    DEFF Research Database (Denmark)

    Ding, Ming; Hvid, I

    2000-01-01

    Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has...... traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial......) cancellous bone. In this study, 160 human proximal tibial cancellous bone specimens from 40 normal donors, aged 16 to 85 years, were collected. These specimens were micro-computed tomography (micro-CT) scanned, then the micro-CT images were segmented using optimal thresholds. From accurate 3-D data sets...

  3. Proton exchange membrane fuel cell model for aging predictions: Simulated equivalent active surface area loss and comparisons with durability tests

    Science.gov (United States)

    Robin, C.; Gérard, M.; Quinaud, M.; d'Arbigny, J.; Bultel, Y.

    2016-09-01

    The prediction of Proton Exchange Membrane Fuel Cell (PEMFC) lifetime is one of the major challenges to optimize both material properties and dynamic control of the fuel cell system. In this study, by a multiscale modeling approach, a mechanistic catalyst dissolution model is coupled to a dynamic PEMFC cell model to predict the performance loss of the PEMFC. Results are compared to two 2000-h experimental aging tests. More precisely, an original approach is introduced to estimate the loss of an equivalent active surface area during an aging test. Indeed, when the computed Electrochemical Catalyst Surface Area profile is fitted on the experimental measures from Cyclic Voltammetry, the computed performance loss of the PEMFC is underestimated. To be able to predict the performance loss measured by polarization curves during the aging test, an equivalent active surface area is obtained by a model inversion. This methodology enables to successfully find back the experimental cell voltage decay during time. The model parameters are fitted from the polarization curves so that they include the global degradation. Moreover, the model captures the aging heterogeneities along the surface of the cell observed experimentally. Finally, a second 2000-h durability test in dynamic operating conditions validates the approach.

  4. Stochastic modeling indicates that aging and somatic evolution in the hematopoetic system are driven by non-cell-autonomous processes.

    Science.gov (United States)

    Rozhok, Andrii I; Salstrom, Jennifer L; DeGregori, James

    2014-12-01

    Age-dependent tissue decline and increased cancer incidence are widely accepted to be rate-limited by the accumulation of somatic mutations over time. Current models of carcinogenesis are dominated by the assumption that oncogenic mutations have defined advantageous fitness effects on recipient stem and progenitor cells, promoting and rate-limiting somatic evolution. However, this assumption is markedly discrepant with evolutionary theory, whereby fitness is a dynamic property of a phenotype imposed upon and widely modulated by environment. We computationally modeled dynamic microenvironment-dependent fitness alterations in hematopoietic stem cells (HSC) within the Sprengel-Liebig system known to govern evolution at the population level. Our model for the first time integrates real data on age-dependent dynamics of HSC division rates, pool size, and accumulation of genetic changes and demonstrates that somatic evolution is not rate-limited by the occurrence of mutations, but instead results from aged microenvironment-driven alterations in the selective/fitness value of previously accumulated genetic changes. Our results are also consistent with evolutionary models of aging and thus oppose both somatic mutation-centric paradigms of carcinogenesis and tissue functional decline. In total, we demonstrate that aging directly promotes HSC fitness decline and somatic evolution via non-cell-autonomous mechanisms.

  5. Assessment Of A Groundwater Flow Model Of The Bangkok Basin, Thailand, Using Carbon-14-Based Ages And Paleohydrology

    Science.gov (United States)

    Sanford, Ward E.; Buapeng, Somkid

    1996-04-01

    A study was undertaken to understand the groundwater flow conditions in the Bangkok Basin, Thailand, by comparing 14C-based and simulated groundwater ages. 14C measurements were made on about 50 water samples taken from wells throughout the basin. Simulated ages were obtained using 1) backward-pathline tracking based on the well locations, and 2) results from a three-dimensional groundwater flow model. Comparisons of ages at these locations reveal a large difference between 14C-based ages and ages predicted by the steady-state groundwater flow model. Mainly, 14C and 13C analyses indicate that groundwater in the Bangkok area is about 20,000 years old, whereas steady-state flow and transport simulations imply that groundwater in the Bangkok area is 50,000-100,000 years old. One potential reason for the discrepancy between simulated and 14C-based ages is the assumption in the model of steady-state flow. Groundwater velocities were probably greater in the region before about 10,000 years ago, during the last glacial maximum, because of the lower position of sea level and the absence of the surficial Bangkok Clay. Paleoflow conditions were estimated and then incorporated into a second set of simulations. The new assumption was that current steady-state flow conditions existed for the last 8,000 years but were preceded by steady-state conditions representative of flow during the last glacial maximum. This "transient" paleohydrologic simulation yielded a mean simulated age that more closely agrees with the mean 14C-based age, especially if the 14C-based age corrected for diffusion into clay layers. Although the uncertainties in both the simulated and 14C-based ages are nontrivial, the magnitude of the improved match in the mean age using a paleohydrologic simulation instead of a steady-state simulation suggests that flow conditions in the basin have changed significantly over the last 10,000-20,000 years. Given that the valid age range of 14C-dating methods and the timing

  6. Use of reflectance spectrophotometry and colorimetry in a general linear model for the determination of the age of bruises.

    Science.gov (United States)

    Hughes, Vanessa K; Langlois, Neil E I

    2010-12-01

    Bruises can have medicolegal significance such that the age of a bruise may be an important issue. This study sought to determine if colorimetry or reflectance spectrophotometry could be employed to objectively estimate the age of bruises. Based on a previously described method, reflectance spectrophotometric scans were obtained from bruises using a Cary 100 Bio spectrophotometer fitted with a fibre-optic reflectance probe. Measurements were taken from the bruise and a control area. Software was used to calculate the first derivative at 490 and 480 nm; the proportion of oxygenated hemoglobin was calculated using an isobestic point method and a software application converted the scan data into colorimetry data. In addition, data on factors that might be associated with the determination of the age of a bruise: subject age, subject sex, degree of trauma, bruise size, skin color, body build, and depth of bruise were recorded. From 147 subjects, 233 reflectance spectrophotometry scans were obtained for analysis. The age of the bruises ranged from 0.5 to 231.5 h. A General Linear Model analysis method was used. This revealed that colorimetric measurement of the yellowness of a bruise accounted for 13% of the bruise age. By incorporation of the other recorded data (as above), yellowness could predict up to 32% of the age of a bruise-implying that 68% of the variation was dependent on other factors. However, critical appraisal of the model revealed that the colorimetry method of determining the age of a bruise was affected by skin tone and required a measure of the proportion of oxygenated hemoglobin, which is obtained by spectrophotometric methods. Using spectrophotometry, the first derivative at 490 nm alone accounted for 18% of the bruise age estimate. When additional factors (subject sex, bruise depth and oxygenation of hemoglobin) were included in the General Linear Model this increased to 31%-implying that 69% of the variation was dependent on other factors. This

  7. Modeling the Impact of Uganda’s Safe Male Circumcision Program: Implications for Age and Regional Targeting

    Science.gov (United States)

    Kripke, Katharine; Vazzano, Andrea; Kirungi, William; Musinguzi, Joshua; Opio, Alex; Ssempebwa, Rhobbinah; Nakawunde, Susan; Kyobutungi, Sheila; Akao, Juliet N.; Magala, Fred; Mwidu, George; Castor, Delivette

    2016-01-01

    Background Uganda aims to provide safe male circumcision (SMC) to 80% of men ages 15–49 by 2016. To date, only 2 million men have received SMC of the 4.2 million men required. In response to age and regional trends in SMC uptake, the country sought to re-examine its targets with respect to age and subnational region, to assess the program’s progress, and to refine the implementation approach. Methods and Findings The Decision Makers’ Program Planning Tool, Version 2.0 (DMPPT 2.0), was used in conjunction with incidence projections from the Spectrum/AIDS Impact Module (AIM) to conduct this analysis. Population, births, deaths, and HIV incidence and prevalence were used to populate the model. Baseline male circumcision prevalence was derived from the 2011 AIDS Indicator Survey. Uganda can achieve the most immediate impact on HIV incidence by circumcising men ages 20–34. This group will also require the fewest circumcisions for each HIV infection averted. Focusing on men ages 10–19 will offer the greatest impact over a 15-year period, while focusing on men ages 15–34 offers the most cost-effective strategy over the same period. A regional analysis showed little variation in cost-effectiveness of scaling up SMC across eight regions. Scale-up is cost-saving in all regions. There is geographic variability in program progress, highlighting two regions with low baseline rates of circumcision where additional efforts will be needed. Conclusion Focusing SMC efforts on specific age groups and regions may help to accelerate Uganda’s SMC program progress. Policy makers in Uganda have already used model outputs in planning efforts, proposing males ages 10–34 as a priority group for SMC in the 2014 application to the Global Fund’s new funding model. As scale-up continues, the country should also consider a greater effort to expand SMC in regions with low MC prevalence. PMID:27410234

  8. Thermal aging modeling and validation on the Mo containing Fe-Cr-Ni alloys

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ying [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tan, Lizhen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Busby, Jeremy T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-04-01

    Thermodynamics of intermetallic phases in Fe-rich Fe-Cr-Ni-Mo alloys is critical knowledge to understand thermal aging effect on the phase stability of Mo-containing austenitic steels, which subsequently facilitates alloy design/improvement and degradation mitigation of these materials for reactor applications. Among the intermetallic phases, Chi (χ), Laves, and Sigma (σ) are often of concern because of their tendency to cause embrittlement of the materials. The focus of this study is thermal stability of the Chi and Laves phases as they were less studied compared to the Sigma phase. Coupled with thermodynamic modeling, thermal stability of intermetallic phases in Mo containing Fe-Cr-Ni alloys was investigated at 1000, 850 and 700 C for different annealing times. The morphologies, compositions and crystal structures of the precipitates of the intermetallic phases were carefully examined by scanning electron microscopy, electron probe microanalysis, X-ray diffraction, and transmission electron microscopy. Three key findings resulted from this study. First, the Chi phase is stable at high temperature, and with decreasing temperature it transforms into the Laves phase that is stable at low temperature. Secondly, Cr, Mo, Ni are soluble in both the Chi and Laves phases, with the solubility of Mo playing a major role in the relative stability of the intermetallic phases. Thirdly, in situ transformation from Chi phase to Laves phase was directly observed, which increased the local strain field, generated dislocations in the intermetallic phases, and altered the precipitate phase orientation relationship with the austenitic matrix. The thermodynamic models that were developed and validated were then applied to evaluating the effect of Mo on the thermal stability of intermetallic phases in type 316 and NF709 stainless steels.

  9. Evaluation of histological changes after tracheal occlusion at different gestational ages in a fetal rat model

    Directory of Open Access Journals (Sweden)

    Rodrigo Melo Gallindo

    2013-01-01

    Full Text Available OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a External control, composed of non-operated rats, and b Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days, divided into triads: 1 Tracheal occlusion, 2 Internal control and 3 Sham (manipulated but not operated. Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001. Histologically, this group had a thicker epithelial thickness (p<0.05 and thinner chondral (p<0.05 and total tracheal thicknesses (p<0.001. These differences were more prominent on gestational days 20.5 and 21.5. CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.

  10. Altered regulation of tau phosphorylation in a mouse model of down syndrome aging.

    Science.gov (United States)

    Sheppard, Olivia; Plattner, Florian; Rubin, Anna; Slender, Amy; Linehan, Jacqueline M; Brandner, Sebastian; Tybulewicz, Victor L J; Fisher, Elizabeth M C; Wiseman, Frances K

    2012-04-01

    Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is associated with an increased risk of Alzheimer's disease (AD). Here, using the unique transchromosomic Tc1 mouse model of DS we investigate the influence of trisomy of Hsa21 on the protein tau, which is hyperphosphorylated in Alzheimer's disease. We show that in old, but not young, Tc1 mice increased phosphorylation of tau occurs at a site suggested to be targeted by the Hsa21 encoded kinase, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A). We show that DYRK1A is upregulated in young and old Tc1 mice, but that young trisomic mice may be protected from accumulating aberrantly phosphorylated tau. We observe that the key tau kinase, glycogen synthase kinase3-β (GSK-3β) is aberrantly phosphorylated at an inhibitory site in the aged Tc1 brain which may reduce total glycogen synthase kinase3-β activity. It is possible that a similar mechanism may also occur in people with DS.

  11. What is the relationship between age and deprivation in influencing emergency hospital admissions? A model using data from a defined, comprehensive, all-age cohort in East Devon, UK

    Science.gov (United States)

    Pereira Gray, Denis; Henley, William; Chenore, Todd; Sidaway-Lee, Kate; Evans, Philip

    2017-01-01

    Objectives To clarify the relationship between social deprivation and age as two factors associated with emergency admissions to hospital. Design Emergency admissions for 12 months were analysed for patients in the NHS NEW Devon CCG. Social deprivation was measured by the Index of Multiple Deprivation (IMD). Logistic regression models estimated the separate and combined effects of social deprivation and age on the risk of emergency admissions for people aged under and over 65. Setting East Devon, UK—area of the NEW Devon CCG. Population 765 861 patients in the CCG database. Main outcome measure Emergency admission to any English hospital. Results Age (p<0.001) and social deprivation (p<0.001) were significantly associated with emergency admission to hospital, but there was a significant interaction between age and social deprivation (p<0.001). From the third quintile of age upwards, age progressively overtakes deprivation and age has a dominant effect on emergency admissions over the age of 65. The effect of age was J-shaped in all deprivation groups, increasing exponentially after age 40. For patients under 65, age and social deprivation had similar risks for emergency admissions, the differences in risk between the top and bottom quintiles of IMD and age being ∼1.5 and 0.9 percentage points. In patients over 65, age had a much greater effect on the risk of admissions than social deprivation, the differences in risk between the top and bottom quintiles of IMD and age being ∼2.8 and 18.7 percentage points. Conclusions Risk curves for all social groups have similar shapes, implying a common biological pattern for ageing in any social group. Over age 65, the biological effects of ageing outweigh the social effects of deprivation. Our model enables CCGs to anticipate and plan for emergency admissions to hospital. These findings provide a new logic for allocating resources to different populations. PMID:28196950

  12. Age Dimension Homeostasis of Physiological Systems, a Slow Dynamics Model in Biology

    Science.gov (United States)

    Kurachi, K.; Yasui, M.; Isobe, T.; Suenaga, E.; Kurachi, S.

    2006-05-01

    Throughout the life span, complex physiological systems are regulated by specific age related mechanisms, thus maintaining the age axis homeostasis. Our efforts for understanding the underlying mechanisms began about a decade ago, successfully discovering the very fist such a mechanism, we called the ASE/AIE-mediated age-related regulatory mechanism of gene expression. This mechanism can explain the major feature of the age-related increase profile of blood coagulation activity. Global analyses of the mouse liver genes and proteins revealed heir highly dynamic and complex age-related regulation, suggesting the existence of several major phases over the life span. These studies facilitate a systematic investigation into the regulatory mechanisms of age-axis homeostasis, a slow dynamics system of the complex biological systems.

  13. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model

    OpenAIRE

    2014-01-01

    As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. Joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factor required for the improvement seen in muscles in old mice in heterochronic parabiosis with young ...

  14. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds.

  15. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    Directory of Open Access Journals (Sweden)

    Caroline eMenard

    2014-05-01

    Full Text Available The LOU/C/Jall (LOU rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn, an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non obese aging

  16. A dynamic model of the marriage market-part 1: matching algorithm based on age preference and availability.

    Science.gov (United States)

    Matthews, A P; Garenne, M L

    2013-09-01

    The matching algorithm in a dynamic marriage market model is described in this first of two companion papers. Iterative Proportional Fitting is used to find a marriage function (an age distribution of new marriages for both sexes), in a stable reference population, that is consistent with the one-sex age distributions of new marriages, and includes age preference. The one-sex age distributions (which are the marginals of the two-sex distribution) are based on the Picrate model, and age preference on a normal distribution, both of which may be adjusted by choice of parameter values. For a population that is perturbed from the reference state, the total number of new marriages is found as the harmonic mean of target totals for men and women obtained by applying reference population marriage rates to the perturbed population. The marriage function uses the age preference function, assumed to be the same for the reference and the perturbed populations, to distribute the total number of new marriages. The marriage function also has an availability factor that varies as the population changes with time, where availability depends on the supply of unmarried men and women. To simplify exposition, only first marriage is treated, and the algorithm is illustrated by application to Zambia. In the second paper, remarriage and dissolution are included.

  17. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease.

    Science.gov (United States)

    Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A; Stevnsner, Tinna

    2012-04-01

    Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of presymptomatic and symptomatic AD mice harboring mutated amyolid precursor protein (APP), Tau, and presinilin-1 (PS1) (3xTgAD). Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed.

  18. Microstructural white matter changes in normal aging: a diffusion tensor imaging study with higher-order polynomial regression models.

    Science.gov (United States)

    Hsu, Jung-Lung; Van Hecke, Wim; Bai, Chyi-Huey; Lee, Cheng-Hui; Tsai, Yuh-Feng; Chiu, Hou-Chang; Jaw, Fu-Shan; Hsu, Chien-Yeh; Leu, Jyu-Gang; Chen, Wei-Hung; Leemans, Alexander

    2010-01-01

    Diffusion tensor imaging (DTI) has already proven to be a valuable tool when investigating both global and regional microstructural white matter (WM) brain changes in the human aging process. Although subject to many criticisms, voxel-based analysis is currently one of the most common and preferred approaches in such DTI aging studies. In this context, voxel-based DTI analyses have assumed a 'linear' correlation when finding the significant brain regions that relate age with a particular diffusion measure of interest. Recent literature, however, has clearly demonstrated 'non-linear' relationships between age and diffusion metrics by using region-of-interest and tractography-based approaches. In this work, we incorporated polynomial regression models in the voxel-based DTI analysis framework to assess age-related changes in WM diffusion properties (fractional anisotropy and axial, transverse, and mean diffusivity) in a large cohort of 346 subjects (25 to 81 years old). Our novel approach clearly demonstrates that voxel-based DTI analyses can greatly benefit from incorporating higher-order regression models when investigating potential relationships between aging and diffusion properties.

  19. Profiling of Age-Related Changes in the Tibialis Anterior Muscle Proteome of the mdx Mouse Model of Dystrophinopathy

    Directory of Open Access Journals (Sweden)

    Steven Carberry

    2012-01-01

    Full Text Available X-linked muscular dystrophy is a highly progressive disease of childhood and characterized by primary genetic abnormalities in the dystrophin gene. Senescent mdx specimens were used for a large-scale survey of potential age-related alterations in the dystrophic phenotype, because the established mdx animal model of dystrophinopathy exhibits progressive deterioration of muscle tissue with age. Since the mdx tibialis anterior muscle is a frequently used model system in muscular dystrophy research, we employed this particular muscle to determine global changes in the dystrophic skeletal muscle proteome. The comparison of mdx mice aged 8 weeks versus 22 months by mass-spectrometry-based proteomics revealed altered expression levels in 8 distinct protein species. Increased levels were shown for carbonic anhydrase, aldolase, and electron transferring flavoprotein, while the expressions of pyruvate kinase, myosin, tropomyosin, and the small heat shock protein Hsp27 were found to be reduced in aged muscle. Immunoblotting confirmed age-dependent changes in the density of key muscle proteins in mdx muscle. Thus, segmental necrosis in mdx tibialis anterior muscle appears to trigger age-related protein perturbations due to dystrophin deficiency. The identification of novel indicators of progressive muscular dystrophy might be useful for the establishment of a muscle subtype-specific biomarker signature of dystrophinopathy.

  20. Current methods in quantifying ROS and oxidative damage in Caenorhabditis elegans and other model organism of aging.

    Science.gov (United States)

    Labuschagne, Christiaan F; Brenkman, Arjan B

    2013-09-01

    Accumulation of oxidative damage has been proposed to be causal to aging as defined by the Free radical Theory of Aging, which has been subject to recent debate. However, a major hurdle in understanding the biological roles of reactive oxygen species (ROS) signaling and their oxidative damage has been the widely recognized methodological difficulties to measure oxidative damage and ROS in vivo. In this review we describe the various novel approaches that have recently been developed to overcome this challenge in the nematode Caenorhabditis elegans, which is a paradigm invertebrate model organism for studying aging and age-related disease given its short lifespan, easy genetics and transparency. In addition, we also discuss these methods in other important model organisms of aging, including the budding yeast Saccharomyces cerevisiae, the fruitfly Drosophila melanogaster and the mouse Mus musculus. After an introduction on the various ROS that can be encountered, we discuss approaches for the detection and quantification of ROS and ROS damage of DNA, lipids and proteins, highlighting examples from literature to demonstrate the applicability and caveats of each method. As will become clear, combinations of approaches have now become possible and will prove essential for thoroughly understanding the involvement of ROS and ROS damage in the biology of aging and disease.

  1. Construction of mass-age curves for the continental crust: An empirical model and an example from the western US

    Science.gov (United States)

    Depaolo, D. J.; Schubert, G. S.; Linn, Ann

    1988-01-01

    The methodology of determining crustal mass-age curves is discussed. Problems in doing this include determination of model ages and accounting for mixing of materials of different ages during crust forming processes. These difficulties can be overcome with some reasonable assumptions and estimates of rock volumes based on areal proportions. This technique was used to construct a reasonably well constrained mass-age curve for the southwestern U.S. based on isotopic measurements on over 100 samples. The results imply that the crust in this area grew episodically at 2.8, 1.8, and 0.1 Ga. It is estimated that it would take on the order of 10000 to 100000 individual Sm-Nd isotopic measurements to carry out a similar exercise for continental crust world wide.

  2. Simulation of Tritium Transport and Groundwater Age in a Variably Saturated 3D Model, Lake Rotorua Catchment, New Zealand

    Science.gov (United States)

    Daughney, C.; Toews, M. W.; Morgenstern, U.; Cornaton, F. J.; Jackson, B. M.

    2013-12-01

    Lake Rotorua is a focus of culture and tourism in New Zealand. The lake's water quality has declined since the 1970s, partly due to nutrient inputs that reach the lake via the groundwater system. Improved land use management within the catchment requires prediction of the spatial variations of groundwater transit time from land surface to the lake, and from this the prediction of current and future nutrient inflows to the lake. This study combines the two main methods currently available for determination of water age: numerical groundwater models and hydrological tracers. A steady-state 3D finite element model was constructed to simulate groundwater flow and transport of tritium and age at the catchment scale (555 km2). The model materials were defined using a 3D geologic model and included ignimbrites, rhyolites, alluvial and lake bottom sediments. The steady-state saturated groundwater flow model was calibrated using observed groundwater levels in boreholes (111 locations) and stream flow measurements from groundwater-fed streams and springs (61 locations). Hydraulic conductivities and Cauchy boundary conditions associated with the streams, springs and lake were parameterized. The transport parameters for the model were calibrated using 191 tritium samples from 105 locations (springs, streams and boreholes), with most locations having two sample dates. The transport model used steady-state flow, but simulated the transient transport and decay of tritium from rainfall recharge between 1945 and 2012. An additional 1D unsaturated sub-model was added to account for tritium decay from the ground surface to the water table. The sub-model is linked on top of the 3D model, and uses the water table depths and material properties from the 3D model. The adjustable calibration parameters for the transport model were porosity and van Genuchten parameters related to the unsaturated sub-models. Calibration of the flow model was achieved using a combination of automated least

  3. Synaptic proteome changes in a DNA repair deficient Ercc1 mouse model of accelerated aging

    NARCIS (Netherlands)

    M.J. Végh (Marlene); M.C. de Waard (Monique); I. van der Pluijm (Ingrid); Y. Ridwan (Yanto); M.J.M. Sassen (Marion J.); P. van Nierop (Pim); R.C. van der Schors (Roel); K.W. Li (Ka Wan); J.H.J. Hoeijmakers (Jan); A.B. Smit (August); R.E. van Kesteren (Ronald)

    2012-01-01

    textabstractCognitive decline is one of the earliest hallmarks of both normal and pathological brain aging. Here we used Ercc1 mutant mice, which are impaired in multiple DNA repair systems and consequently show accelerated aging and progressive memory deficits, to identify changes in the levels of

  4. Pension Funds' Asset Allocation and Participant Age : A Test of the Life-Cycle Model

    NARCIS (Netherlands)

    Bikker, J.A.; Broeders, D.W.G.A.; Hollanders, D.A.; Ponds, E.H.M.

    2009-01-01

    This paper examines the impact of participants’ age distribution on the asset allocation of Dutch pension funds, using a unique data set of pension fund investment plans for 2007. Theory predicts a negative effect of age on (strategic) equity exposures. We observe that pension funds do indeed take t

  5. Research on the Healthy Lifestyle Model, Active Ageing, and Loneliness of Senior Learners

    Science.gov (United States)

    Hung, Jui-Ying; Lu, Kuo-Song

    2014-01-01

    Taiwan has the fastest ageing population in the world. Thus, the government and local policy makers need to formulate policies not just for the nursing and care needs of the aged. They also need to actively promote the need for lifelong learning among seniors in order to achieve elderly-friendly objectives, such as health promotion and delays in…

  6. Age-distribution estimation for karst groundwater: Issues of parameterization and complexity in inverse modeling by convolution

    Science.gov (United States)

    Long, A.J.; Putnam, L.D.

    2009-01-01

    Convolution modeling is useful for investigating the temporal distribution of groundwater age based on environmental tracers. The framework of a quasi-transient convolution model that is applicable to two-domain flow in karst aquifers is presented. The model was designed to provide an acceptable level of statistical confidence in parameter estimates when only chlorofluorocarbon (CFC) and tritium (3H) data are available. We show how inverse modeling and uncertainty assessment can be used to constrain model parameterization to a level warranted by available data while allowing major aspects of the flow system to be examined. As an example, the model was applied to water from a pumped well open to the Madison aquifer in central USA with input functions of CFC-11, CFC-12, CFC-113, and 3H, and was calibrated to several samples collected during a 16-year period. A bimodal age distribution was modeled to represent quick and slow flow less than 50 years old. The effects of pumping and hydraulic head on the relative volumetric fractions of these domains were found to be influential factors for transient flow. Quick flow and slow flow were estimated to be distributed mainly within the age ranges of 0-2 and 26-41 years, respectively. The fraction of long-term flow (>50 years) was estimated but was not dateable. The different tracers had different degrees of influence on parameter estimation and uncertainty assessments, where 3H was the most critical, and CFC-113 was least influential.

  7. demogR: A Package for the Construction and Analysis of Age-structured Demographic Models in R

    Directory of Open Access Journals (Sweden)

    James Holland Jones

    2007-08-01

    Full Text Available The analysis of matrix population models has become a fundamental tool in ecology, conservation biology, and life history theory. In this paper, I present demogR, a package for analyzing age-structured population models in R. The package includes tools for the construction and analysis of matrix population models. In addition to the standard analyses commonly used in evolutionary demography and conservation biology, demogR contains a variety of tools from classical demography. This includes the construction of period life tables, and the generation of model mortality and fertility schedules for human populations. The tools in demogR are generally applicable to age-structured populations but are particularly useful for analyzing problems in human ecology. I illustrate some of the capabilities of the package by doing an evolutionary demographic analysis of several human populations.

  8. Application of IEUBK model in lead risk assessment of children aged 61–84 months old in central China

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan [MOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Hu, Jia [Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu (China); Wu, Wei [MOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Liu, Shuyun [Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Li, Mei [Hanyang Center for Disease Prevention and Control, Wuhan, Hubei (China); Yao, Na; Chen, Jianwei [MOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Ye, Linxiang [Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Wang, Qi, E-mail: lwq95@126.com [MOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China); Zhou, Yikai, E-mail: zhouyk@mails.tjmu.edu.cn [MOE Key Lab of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei (China)

    2016-01-15

    Few studies have focused on the accuracy of using the Integrated Exposure Uptake Biokinetic (IEUBK) model in Chinese children with site- and age-specific exposure data. This study aimed to validate the accuracy and sensitivity of the IEUBK model in lead risk assessment of Chinese children aged 61–84 months old. A total of 760 children were enrolled from two respective counties in Central China by using random cluster sampling method. Blood lead levels (BLLs) of all subjects were determined using graphite furnace atomic absorption spectrometry, as well as that in the environmental media, such as air, drinking water, soil, dust and food. Age- and site-specific time-activity patterns and water consumption were evaluated by using questionnaires for children. Exposure parameters including outdoor and indoor activity time, ventilation rate and water consumption in this study were different from the default values of the IEUBK model. Statistical analysis revealed no significant differences between the predicted and observed BLLs. Diet and soil/dust lead intake contributed approximately 83.39% (57.40%–93.84% range) and 15.18% (3.25%–41.60% range) of total lead intake, respectively. These findings showed that the IEUBK model is suitable for lead risk assessment of Chinese children aged 61–84 months old and diet acts as an important lead source. - Highlights: • The first time to fit and discuss the IEUBK model in China based on comprehensive local children exposure parameters. • Two different exposure scenarios to apply the IEUBK model in different conditions. • The first time to report the ventilation rate in Chinese children aged 61 to 84 months. • Highlight the role of dietary to lead intake for Chinese children.

  9. A Novel Approach for Analysis of the Log-Linear Age-Period-Cohort Model: Application to Lung Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Tengiz Mdzinarishvili

    2009-12-01

    Full Text Available A simple, computationally efficient procedure for analyses of the time period and birth cohort effects on the distribution of the age-specific incidence rates of cancers is proposed. Assuming that cohort effects for neighboring cohorts are almost equal and using the Log-Linear Age-Period-Cohort Model, this procedure allows one to evaluate temporal trends and birth cohort variations of any type of cancer without prior knowledge of the hazard function. This procedure was used to estimate the influence of time period and birth cohort effects on the distribution of the age-specific incidence rates of first primary, microscopically confirmed lung cancer (LC cases from the SEER9 database. It was shown that since 1975, the time period effect coefficients for men increase up to 1980 and then decrease until 2004. For women, these coefficients increase from 1975 up to 1990 and then remain nearly constant. The LC birth cohort effect coefficients for men and women increase from the cohort of 1890–94 until the cohort of 1925–29, then decrease until the cohort of 1950–54 and then remain almost unchanged. Overall, LC incidence rates, adjusted by period and cohort effects, increase up to the age of about 72–75, turn over, and then fall after the age of 75–78. The peak of the adjusted rates in men is around the age of 77–78, while in women, it is around the age of 72–73. Therefore, these results suggest that the age distribution of the incidence rates in men and women fall at old ages.

  10. Modelling Cost Effectiveness in Neovascular Age-Related Macular Degeneration: The Impact of Using Contrast Sensitivity vs. Visual Acuity.

    OpenAIRE

    Butt, T.; Patel,P J; Tufail, A; Rubin, G. S.

    2014-01-01

    The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neov...

  11. Evidence-Based Systematic Review: Effects of Different Service Delivery Models on Communication Outcomes for Elementary School-Age Children

    Science.gov (United States)

    Cirrin, Frank M.; Schooling, Tracy L.; Nelson, Nickola W.; Diehl, Sylvia F.; Flynn, Perry F.; Staskowski, Maureen; Torrey, T. Zoann; Adamczyk, Deborah F.

    2010-01-01

    Purpose: The purpose of this investigation was to conduct an evidence-based systematic review (EBSR) of peer-reviewed articles from the last 30 years about the effect of different service delivery models on speech-language intervention outcomes for elementary school-age students. Method: A computer search of electronic databases was conducted to…

  12. Effects of Video Self-Modeling on Eliminating Public Undressing by Elementary-Aged Students with Developmental Disabilities during Urination

    Science.gov (United States)

    Ohtake, Yoshihisa; Takeuchi, Ai; Watanabe, Kentaro

    2014-01-01

    This study investigated the effectiveness of video self-modeling (VSM) for eliminating the public undressing of two elementary-aged students with developmental disabilities during urination. A multiple-probe design across participants revealed that the degree of exposed body parts decreased immediately after introduction of VSM. However, exposure…

  13. Age modelling for Pleistocene lake sediments : A comparison of methods from the Andean Fuquene Basin (Colombia) case study

    NARCIS (Netherlands)

    Groot, Mirella H. M.; van der Plicht, Johannes; Hooghiemstra, Henry; Lourens, Lucas J.; Rowe, Harold D.

    2014-01-01

    Challenges and pitfalls for developing age models for long lacustrine sedimentary records are discussed and a comparison is made between radiocarbon dating, visual curve matching, and frequency analysis in the depth domain in combination with cyclostratigraphy. A core section of the high resolution

  14. Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging.

    Directory of Open Access Journals (Sweden)

    W Edward Visser

    Full Text Available DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/- or intermediate (Ercc1-/Δ-7 progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging.

  15. Evaluation of unconstrained and constrained mathematical functions to model girth growth of rubber trees (Hevea brasiliensis) using young age measurements

    Institute of Scientific and Technical Information of China (English)

    T. R. Chandrasekhar

    2012-01-01

    No attempt has been made to date to model growth in girth of rubber tree (Hevea brasiliansis).We evaluated the few widely used growth functions to identify the most parsimonious and biologically reasonable model for describing the girth growth of young rubber trees based on an incomplete set of young age measurements.Monthly data for girth of immature trees (age 2 to 12 years) from two locations were subjected to modelling.Re-parameterized,unconstrained and constrained growth functions of Richards (RM),Gompertz (GM) and the monomolecular model (MM) were fitted to data.Duration of growth was the constraint introduced.In the first stage,we attempted a population average (PA) model to capture the trend in growth.The best PA model was fitted as a subject specific (SS) model.We used appropriate error variance-covariance structure to account for correlation due to repeated measurements over time.Unconstrained functions underestimated the asymptotic maximum that did not reflect the carrying capacity of the locations.Underestimations were attributed to the partial set of measurements made during the early growth phase of the trees.MM proved superior to RM and GM.In the random coefficient models,both Gf and G0 appeared to be influenced by tree level effects.Inclusion of diagonal definite positive matrix removed the correlation between random effects.The results were similar at both locations.In the overall assessment MM appeared as the candidate model for studying the girth-age relationships in Hevea trees.Based on the fitted model we conclude that,in Hevea trees,growth rate is maintained at maximum value at t0,then decreases until the final state at dG/dt ≥ 0,resulting in yield curve with no period of accelerating growth.One physiological explanation is that photosynthetic activity in Hevea trees decreases as girth increases and constructive metabolism is larger than destructive metabolism.

  16. Age-related decline in white matter tract integrity and cognitive performance: a DTI tractography and structural equation modeling study.

    Science.gov (United States)

    Voineskos, Aristotle N; Rajji, Tarek K; Lobaugh, Nancy J; Miranda, Dielle; Shenton, Martha E; Kennedy, James L; Pollock, Bruce G; Mulsant, Benoit H

    2012-01-01

    Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.

  17. Effects of Dimethylaminoethanol and Compound Amino Acid on D-Galactose Induced Skin Aging Model of Rat

    Directory of Open Access Journals (Sweden)

    Su Liu

    2014-01-01

    Full Text Available A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE and compound amino acid (AA in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat.

  18. Kinetic Model of Optical Characteristics of Banknote Paper During Artificial Aging

    Science.gov (United States)

    Kulak, M. I.; Kyrychok, T. Yu.; Miadziak, D. M.; Kyrychok, P. O.

    2016-09-01

    A phenomenological kinetic equation is obtained for the change in color difference and brightness of banknote paper during aging. A solution is obtained for the kinetic equation. The coefficients of the kinetic function are determined from experimental data. Kinetic functions are constructed for three samples of the banknote paper. By analysis of the coefficients of the kinetic function it is possible to compare the paper according to its resistance towards the aging process.

  19. Haemophilus influenzae LicB contributes to lung damage in an aged mice co-infection model.

    Science.gov (United States)

    Bondy, Jessica; Osharovich, Sofya; Storm, Julie; Durning, Graham; McAuliffe, Timothy; Fan, Xin

    2016-01-01

    Phosphorylcholine (ChoP) decoration of lipopolysaccharides is an important virulence strategy adopted by Haemophilus influenzae to establish a niche on the mucosal surface and to promote adherence to the host cells. The incorporation of ChoP on the LPS surface involves the lic1 operon, which consists of the licA, licB, licC, and licD genes. Among which, licB is a choline transporter gene required for acquisition of choline from environmental sources. In this study, we investigated the pathogenesis of the licB gene in an aged mice infection model. Due to immediate clearance of H. influenzae upon infection in mice, we employed influenza A virus and H. influenzae co-infection model. Our data showed that in the co-infection model, the secondary bacterial infection with a very low H. influenzae concentration of 100 colony forming unit is lethal to the aged mice. Although we did not observe any differences in weight loss between parent and licB mutant strains during the course of infection, a significant reduction of lung tissue damage was observed in the licB mutant infected aged mice. These results suggest that the licB gene is a virulence factor during H. influenzae infection in the lung in aged mice, possibly due to the increased binding to the host cell receptor via ChoP expression on the bacterial surface. In addition, when aged mice and mature mice were compared in the challenge experiments, we did not observe any protective immunity in the co-infection model suggesting the detrimental effects of the secondary bacterial infection on the aged mice in contrast to obvious immune-protections observed in the mature mice. The results of our experiments also implied that the co-infection model with influenza A virus and H. influenzae may be employed as a model system to study H. influenzae pathogenesis in vivo in aged mice.

  20. Stem cell therapies in preclinical models of stroke associated with aging

    Directory of Open Access Journals (Sweden)

    Aurel ePopa-Wagner

    2014-11-01

    Full Text Available Stroke has limited treatment options, demanding a vigorous search for new therapeutic strategies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments related to unfavorable environments that are in part related to aging processes. Since stroke afflicts mostly the elderly, it is highly desirable and clinically important to test the efficacy of cell therapies in aged brain microenvironments. Although widely believed to be refractory to regeneration, recent studies using both neural precursor cells and bone marrow-derived mesenchymal stem cells for stroke therapy suggest that the aged rat brain is not refractory to cell-based therapy, and that it also supports plasticity and remodeling. Yet, important differences exist in the aged compared with young brain, i.e., the accelerated progression of ischemic injury to brain infarction, the reduced rate of endogenous neurogenesis and the delayed initiation of neurological recovery. Pitfalls in the development of cell-based therapies may also be related to age-associated comorbidities, e.g., diabetes or hyperlipidemia, which may result in maladaptive or compromised brain remodeling, respectively. These age-related aspects should be carefully considered in the clinical translation of restorative therapies.

  1. Drifting through basic subprocesses of reading: A hierarchical diffusion model analysis of age effects on visual word recognition

    Directory of Open Access Journals (Sweden)

    Eva Froehlich

    2016-11-01

    Full Text Available Reading is one of the most popular leisure activities and it is routinely performed by most individuals even in old age. Successful reading enables older people to master and actively participate in everyday life and maintain functional independence. Yet, reading comprises a multitude of subprocesses and it is undoubtedly one of the most complex accomplishments of the human brain. Not surprisingly, findings of age-related effects on word recognition and reading have been partly contradictory and are often confined to only one of four central reading subprocesses, i.e., sublexical, orthographic, phonological and lexico-semantic processing. The aim of the present study was therefore to systematically investigate the impact of age on each of these subprocesses. A total of 1,807 participants (young, N = 384; old, N = 1,423 performed four decision tasks specifically designed to tap one of the subprocesses. To account for the behavioral heterogeneity in older adults, this subsample was split into high and low performing readers. Data were analyzed using a hierarchical diffusion modelling approach which provides more information than standard response times/accuracy analyses. Taking into account incorrect and correct response times, their distributions and accuracy data, hierarchical diffusion modelling allowed us to differentiate between age-related changes in decision threshold, non-decision time and the speed of information uptake. We observed longer non-decision times for older adults and a more conservative decision threshold. More importantly, high-performing older readers outperformed younger adults at the speed of information uptake in orthographic and lexico-semantic processing whereas a general age-disadvantage was observed at the sublexical and phonological levels. Low-performing older readers were slowest in information uptake in all four subprocesses. Discussing these results in terms of computational models of word recognition, we propose

  2. Drifting through Basic Subprocesses of Reading: A Hierarchical Diffusion Model Analysis of Age Effects on Visual Word Recognition

    Science.gov (United States)

    Froehlich, Eva; Liebig, Johanna; Ziegler, Johannes C.; Braun, Mario; Lindenberger, Ulman; Heekeren, Hauke R.; Jacobs, Arthur M.

    2016-01-01

    Reading is one of the most popular leisure activities and it is routinely performed by most individuals even in old age. Successful reading enables older people to master and actively participate in everyday life and maintain functional independence. Yet, reading comprises a multitude of subprocesses and it is undoubtedly one of the most complex accomplishments of the human brain. Not surprisingly, findings of age-related effects on word recognition and reading have been partly contradictory and are often confined to only one of four central reading subprocesses, i.e., sublexical, orthographic, phonological and lexico-semantic processing. The aim of the present study was therefore to systematically investigate the impact of age on each of these subprocesses. A total of 1,807 participants (young, N = 384; old, N = 1,423) performed four decision tasks specifically designed to tap one of the subprocesses. To account for the behavioral heterogeneity in older adults, this subsample was split into high and low performing readers. Data were analyzed using a hierarchical diffusion modeling approach, which provides more information than standard response time/accuracy analyses. Taking into account incorrect and correct response times, their distributions and accuracy data, hierarchical diffusion modeling allowed us to differentiate between age-related changes in decision threshold, non-decision time and the speed of information uptake. We observed longer non-decision times for older adults and a more conservative decision threshold. More importantly, high-performing older readers outperformed younger adults at the speed of information uptake in orthographic and lexico-semantic processing, whereas a general age-disadvantage was observed at the sublexical and phonological levels. Low-performing older readers were slowest in information uptake in all four subprocesses. Discussing these results in terms of computational models of word recognition, we propose age

  3. Evaluation of alternative age-based methods for estimating relative abundance from survey data in relation to assessment models

    DEFF Research Database (Denmark)

    Berg, Casper Willestofte; Nielsen, Anders; Kristensen, Kasper

    2014-01-01

    Indices of abundance from fishery-independent trawl surveys constitute an important source of information for many fish stock assessments. Indices are often calculated using area stratified sample means on age-disaggregated data, and finally treated in stock assessment models as independent...... observations. We evaluate a series of alternative methods for calculating indices of abundance from trawl survey data (delta-lognormal, delta-gamma, and Tweedie using Generalized Additive Models) as well as different error structures for these indices when used as input in an age-based stock assessment model...... the different indices produced. The stratified mean method is found much more imprecise than the alternatives based on GAMs, which are found to be similar. Having time-varying index variances is found to be of minor importance, whereas the independence assumption is not only violated but has significant impact...

  4. EXTINCTION AND WAVEFRONT IN AN AGE-STRUCTURED POPULATION MODEL ON INFINITE PATCHES WITH DISTRIBUTED MATURATION DELAY

    Institute of Scientific and Technical Information of China (English)

    LING Jiaoxiu; WENG Peixuan

    2005-01-01

    In this paper, we derive a lattice model for a single species on infinite patches of one-dimensional space with that the maturatio