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

Science.gov (United States)

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. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Cloning, sequencing, and transgenic expression of Podospora curvicolla and Sordaria macrospora eEF1A genes: relationship between cytosolic translation and longevity in filamentous fungi.

Science.gov (United States)

Gagny, B; Rossignol, M; Silar, P

1997-12-01

We have cloned and sequenced the gene encoding the translation elongation factor eEF1A from two filamentous fungi, Podospora curvicolla and Sordaria macrospora. These fungi are close relatives of Podospora anserina and also show senescence syndromes. Comparison of the sequences of the deduced proteins with that of P. anserina reveals that the three proteins differ in several positions. Replacement of the P. anserina gene by either of the two exogenous genes does not entail any modification in P. anserina physiology; the longevity of the fungus is not affected. No alteration of in vivo translational accuracy was detected; however, the exogenous proteins nonetheless promoted a modification of the resistance to the aminoglycoside antibiotic paromomycin. These data suggest that optimization of life span between these closely related fungi has likely not been performed during evolution through modifications of eEF1A activity, despite the fact that mutations in this factor can drastically affect longevity. Copyright 1997 Academic Press.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

Lalucque, Hervé; Silar, Philippe

2000-01-01

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. PMID:11112985

IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.

Science.gov (United States)

Lalucque, Hervé; Malagnac, Fabienne; Green, Kimberly; Gautier, Valérie; Grognet, Pierre; Chan Ho Tong, Laetitia; Scott, Barry; Silar, Philippe

2017-01-15

Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Inositol-phosphate signaling as mediator for growth and sexual reproduction in Podospora anserina.

Science.gov (United States)

Xie, Ning; Ruprich-Robert, Gwenaël; Chapeland-Leclerc, Florence; Coppin, Evelyne; Lalucque, Hervé; Brun, Sylvain; Debuchy, Robert; Silar, Philippe

2017-09-01

The molecular pathways involved in the development of multicellular fruiting bodies in fungi are still not well known. Especially, the interplay between the mycelium, the female tissues and the zygotic tissues of the fruiting bodies is poorly documented. Here, we describe PM154, a new strain of the model ascomycetes Podospora anserina able to mate with itself and that enabled the easy recovery of new mutants affected in fruiting body development. By complete genome sequencing of spod1, one of the new mutants, we identified an inositol phosphate polykinase gene as essential, especially for fruiting body development. A factor present in the wild type and diffusible in mutant hyphae was able to induce the development of the maternal tissues of the fruiting body in spod1, but failed to promote complete development of the zygotic ones. Addition of myo-inositol in the growth medium was able to increase the number of developing fruiting bodies in the wild type, but not in spod1. Overall, the data indicated that inositol and inositol polyphosphates were involved in promoting fruiting body maturation, but also in regulating the number of fruiting bodies that developed after fertilization. The same effect of inositol was seen in two other fungi, Sordaria macrospora and Chaetomium globosum. Key role of the inositol polyphosphate pathway during fruiting body maturation appears thus conserved during the evolution of Sordariales fungi. Copyright © 2017 Elsevier Inc. All rights reserved.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration▿ †

OpenAIRE

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-01-01

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 inv...

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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Wood Utilization Is Dependent on Catalase Activities in the Filamentous Fungus Podospora anserina

Science.gov (United States)

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 H2O2 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. PMID:22558065

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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.

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

Science.gov (United States)

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

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. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

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. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

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.

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

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

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

Science.gov (United States)

Bidard, Frédérique; Imbeaud, Sandrine; Reymond, Nancie; Lespinet, Olivier; Silar, Philippe; Clavé, Corinne; Delacroix, Hervé; Berteaux-Lecellier, Véronique; Debuchy, Robert

2010-06-18

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. 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. 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.

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.

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

2007-01-01

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. PMID:17933907

eEF1A Controls ascospore differentiation through elevated accuracy, but controls longevity and fruiting body formation through another mechanism in Podospora anserina.

Science.gov (United States)

Silar, P; Lalucque, H; Haedens, V; Zickler, D; Picard, M

2001-01-01

Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously shown to impair ascospore formation, to drastically increase life span, and to permit the development of the Crippled Growth degenerative process. Here, we show that eEF1A controls ascospore formation through accuracy level maintenance. Examination of antisuppressor mutant perithecia reveals two main cytological defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression levels are shown to be highly dependent upon both the mutation site and the suppressor used, precluding any correlation between antisuppression efficiency and severity of the sporulation impairment. Nevertheless, severity of ascospore differentiation defect is correlated with resistance to paromomycin. We also show that eEF1A controls fruiting body formation and longevity through a mechanism(s) different from accuracy control. In vivo, GFP tagging of the protein in a way that partly retains its function confirmed earlier cytological observation; i.e., this factor is mainly diffuse within the cytosol, but may transiently accumulate within nuclei or in defined regions of the cytoplasm. These data emphasize the fact that the translation apparatus exerts a global regulatory control over cell physiology and that eEF1A is one of the key factors involved in this monitoring. PMID:11514440

Heterologous production of cellobiose dehydrogenases from the basidiomycete Coprinopsis cinerea and the ascomycete Podospora anserina and their effect on saccharification of wheat straw.

Science.gov (United States)

Turbe-Doan, Annick; Arfi, Yonathan; Record, Eric; Estrada-Alvarado, Isabel; Levasseur, Anthony

2013-06-01

Cellobiose dehydrogenases (CDHs) are extracellular glycosylated haemoflavoenzymes produced by many different wood-degrading and phytopathogenic fungi. Putative cellobiose dehydrogenase genes are recurrently discovered by genome sequencing projects in various phylogenetically distinct fungi. The genomes from the basidiomycete Coprinopsis cinerea and the ascomycete Podospora anserina were screened for candidate cdh genes, and one and three putative gene models were evidenced, respectively. Two putative cdh genes were selected and successfully expressed for the first time in Aspergillus niger. CDH activity was measured for both constructions (CDHcc and CDHpa), and both recombinant CDHs were purified to homogeneity and subsequently characterised. Kinetic constants were determined for several carbohydrates including β-1,4-linked di- and oligosaccharides. Optimal temperature and pH were 60 °C and 5 for CDHcc and 65-70 °C and 6 for CDHpa. Both CDHs showed a broad range of pH stability between 4 and 8. The effect of both CDHs on saccharification of micronized wheat straw by an industrial Trichoderma reesei secretome was determined. The addition of each CDH systematically decreased the release of total reducing sugars, but to different extents and according to the CDH concentration. Analytical methods were carried out to quantify the release of glucose, xylose and gluconic acid. An increase of glucose and xylose was measured at a low CDHcc concentration. At moderated and high CDHcc and CDHpa concentrations, glucose was severely reduced with a concomitant increase of gluconic acid. In conclusion, these results give new insights into the physical and chemical parameters and diversity of basidiomycetous and ascomycetous CDHs. These findings also demonstrated that CDH drastically influenced the saccharification on a natural substrate, and thus, CDH origin, concentration and potential enzymatic partners should be carefully considered in future artificial secretomes for

Modeled ground water age distributions

Science.gov (United States)

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.

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.

Model galena ages from Karnataka and surrounding ages

Energy Technology Data Exchange (ETDEWEB)

Venkatasubramanian, V S [Indian Inst. of Science, Bangalore. Dept. of Physics; Radhakrishna, B P [Geological Society of India, Bangalore; Jayaram, S [Department of Mines and Geology, Bangalore

1977-02-01

Lead isotope ratios have been measured for selected samples from the Chitradurga and Kolar schist belts, the high-grade gneisses E of Karnataka (in Tamil Nadu) and Agnigundala of Cuddapah. Most of the isotope data approximately fit a single-stage model and yield model age at 3000 m.y., 2500 m.y., 1400 m.y. and 1100 m.y. The relations with other available age data are discussed.

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. Copyright © 2012 Elsevier Inc. All rights reserved.

C. elegans model of neuronal aging

OpenAIRE

Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

2011-01-01

Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

Risk evaluations of aging phenomena: the linear aging reliability model and its extensions

International Nuclear Information System (INIS)

Vesely, W.E.

1987-01-01

A model for component failure rates due to aging mechanisms has been developed from basic phenomenological considerations. In the treatment, the occurrences of deterioration are modeled as following a Poisson process. The severity of damage is allowed to have any distribution, however the damage is assumed to accumulate independently. Finally, the failure rate is modeled as being proportional to the accumulated damage. Using this treatment, the linear aging failure rate model is obtained. The applicability of the linear aging model to various mechanisms is discussed. The model can be extended to cover nonlinear and dependent aging phenomena. The implementability of the linear aging model is demonstrated by applying it to the aging data collected in NRC's Nuclear Plant Aging Research (NPAR) Program. The applications show that aging as observed in collected data have significant effects on the component failure probability and component reliability when aging is not effectively detected and controlled by testing and maintenance

Risk evaluations of aging phenomena: The linear aging reliability model and its extensions

International Nuclear Information System (INIS)

Vesely, W.E.

1986-01-01

A model for component failure rates due to aging mechanisms has been developed from basic phenomenological considerations. In the treatment, the occurrences of deterioration are modeled as following a Poisson process. The severity of damage is allowed to have any distribution, however the damage is assumed to accumulate independently. Finally, the failure rate is modeled as being proportional to the accumulated damage. Using this treatment, the linear aging failure rate model is obtained. The applicability of the linear aging model to various mechanisms is discussed. The model can be extended to cover nonlinear and dependent aging phenomena. The implementability of the linear aging model is demonstrated by applying it of the aging data collected in NRC's Nuclear Plant Aging Research (NPAR) Program. The applications show that aging as observed in collected data have significant effects on the component failure probability and component reliability when aging is not effectively detected and controlled by testing and maintenance

Risk evaluations of aging phenomena: The linear aging reliability model and its extensions

International Nuclear Information System (INIS)

Vesely, W.E.; Wolford, A.J.

1988-01-01

A model for component failure rates due to aging mechanisms is developed from basic phenomenological considerations. In the treatment, the occurrences of deterioration are modeled as following a Poisson process. The severity of damage is allowed to have any distribution, however the damage is assumed to accumulate independently. Finally, the failure rate is modeled as being proportional to the accumulated damage. Using this treatment, the linear aging failure rate model is obtained. The applicability of the linear aging model to various mechanisms is discussed. Extensions of the model to cover nonlinear and dependent aging phenomena are also described. The implementability of the linear aging model is demonstrated by applying it to the aging data collected in the U.S. NRC Nuclear Plant Aging Research (NPAR) Program. (orig./HP)

The ura5 gene of the ascomycete Sordaria macrospora: molecular cloning, characterization and expression in Escherichia coli.

Science.gov (United States)

Le Chevanton, L; Leblon, G

1989-04-15

We cloned the ura5 gene coding for the orotate phosphoribosyl transferase from the ascomycete Sordaria macrospora by heterologous probing of a Sordaria genomic DNA library with the corresponding Podospora anserina sequence. The Sordaria gene was expressed in an Escherichia coli pyrE mutant strain defective for the same enzyme, and expression was shown to be promoted by plasmid sequences. The nucleotide sequence of the 1246-bp DNA fragment encompassing the region of homology with the Podospora gene has been determined. This sequence contains an open reading frame of 699 nucleotides. The deduced amino acid sequence shows 72% similarity with the corresponding Podospora protein.

Characterization of three multicopper oxidases in the filamentous fungus Podospora anserina: A new role of an ABR1-like protein in fungal development?

Science.gov (United States)

Xie, Ning; Ruprich-Robert, Gwenaël; Silar, Philippe; Herbert, Eric; Ferrari, Roselyne; Chapeland-Leclerc, Florence

2018-07-01

The Podospora anserina genome contains a large family of 15 multicopper oxidases (MCOs), including three genes encoding a FET3-like protein, an ABR1-like protein and an ascorbate oxidase (AO)-like protein. FET3, ABR1 and AO1 are involved in global laccase-like activity since deletion of the relevant genes led to a decrease of activity when laccase substrate (ABTS) was used as substrate. However, contrary to the P. anserina MCO proteins previously characterized, none of these three MCOs seemed to be involved in lignocellulose degradation and in resistance to phenolic compounds and oxidative stress. We showed that the bulk of ferroxidase activity was clearly due to ABR1, and only in minor part to FET3, although ABR1 does not contain all the residues typical of FET3 proteins. Moreover, we showed that ABR1, related to the Aspergillus fumigatus ABR1 protein, was clearly and specifically involved in pigmentation of ascospores. Surprisingly, phenotypes were more severe in mutants lacking both abr1 and ao1. Deletion of the ao1 gene led to an almost total loss of AO activity. No direct involvement of AO1 in fungal developmental process in P. anserina was evidenced, except in a abr1 Δ background. Overall, unlike other previously characterized MCOs, we thus evidence a clear involvement of ABR1 protein in fungal development. Copyright © 2018 Elsevier Inc. All rights reserved.

Pavement Aging Model by Response Surface Modeling

Directory of Open Access Journals (Sweden)

Manzano-Ramírez A.

2011-10-01

Full Text Available In this work, surface course aging was modeled by Response Surface Methodology (RSM. The Marshall specimens were placed in a conventional oven for time and temperature conditions established on the basis of the environment factors of the region where the surface course is constructed by AC-20 from the Ing. Antonio M. Amor refinery. Volatilized material (VM, load resistance increment (ΔL and flow resistance increment (ΔF models were developed by the RSM. Cylindrical specimens with real aging were extracted from the surface course pilot to evaluate the error of the models. The VM model was adequate, in contrast (ΔL and (ΔF models were almost adequate with an error of 20 %, that was associated with the other environmental factors, which were not considered at the beginning of the research.

Mixed models, linear dependency, and identification in age-period-cohort models.

Science.gov (United States)

O'Brien, Robert M

2017-07-20

This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Mathematical Model of Age Aggression

OpenAIRE

Golovinski, P. A.

2013-01-01

We formulate a mathematical model of competition for resources between representatives of different age groups. A nonlinear kinetic integral-differential equation of the age aggression describes the process of redistribution of resources. It is shown that the equation of the age aggression has a stationary solution, in the absence of age-dependency in the interaction of different age groups. A numerical simulation of the evolution of resources for different initial distributions has done. It ...

D-galactose-induced brain ageing model

DEFF Research Database (Denmark)

Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

2017-01-01

Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

Exactly solvable models of growing interfaces and lattice gases: the Arcetri models, ageing and logarithmic sub-ageing

Science.gov (United States)

Durang, Xavier; Henkel, Malte

2017-12-01

Motivated by an analogy with the spherical model of a ferromagnet, the three Arcetri models are defined. They present new universality classes, either for the growth of interfaces, or else for lattice gases. They are distinct from the common Edwards-Wilkinson and Kardar-Parisi-Zhang universality classes. Their non-equilibrium evolution can be studied by the exact computation of their two-time correlators and responses. In both interpretations, the first model has a critical point in any dimension and shows simple ageing at and below criticality. The exact universal exponents are found. The second and third model are solved at zero temperature, in one dimension, where both show logarithmic sub-ageing, of which several distinct types are identified. Physically, the second model describes a lattice gas and the third model describes interface growth. A clear physical picture on the subsequent time and length scales of the sub-ageing process emerges.

System Models and Aging: A Driving Example.

Science.gov (United States)

Melichar, Joseph F.

Chronological age is a marker in time but it fails to measure accurately the performance or behavioral characteristics of individuals. This paper models the complexity of aging by using a system model and a human function paradigm. These models help facilitate representation of older adults, integrate research agendas, and enhance remediative…

Age-related changes in the mitochondrial proteome of the fungus Podospora anserina analyzed by 2D-DIGE and LC-MS/MS

NARCIS (Netherlands)

Chimi, M.A.; Drose, S.; Wittig, I.; Heide, H.; Steger, M.; Werner, A.; Hamann, A.; Osiewacz, H.D.; Brandt, U.

2013-01-01

Many questions concerning the molecular processes during biological aging remain unanswered. Since mitochondria are central players in aging, we applied quantitative two-dimensional difference gel electrophoresis (2D-DIGE) coupled to protein identification by mass spectrometry to study the

The potential of artificial aging for modelling of natural aging processes of ballpoint ink.

Science.gov (United States)

Weyermann, Céline; Spengler, Bernhard

2008-08-25

Artificial aging has been used to reproduce natural aging processes in an accelerated pace. Questioned documents were exposed to light or high temperature in a well-defined manner in order to simulate an increased age. This may be used to study the aging processes or to date documents by reproducing their aging curve. Ink was studied especially because it is deposited on the paper when a document, such as a contract, is produced. Once on the paper, aging processes start through degradation of dyes, solvents drying and resins polymerisation. Modelling of dye's and solvent's aging was attempted. These processes, however, follow complex pathways, influenced by many factors which can be classified as three major groups: ink composition, paper type and storage conditions. The influence of these factors is such that different aging states can be obtained for an identical point in time. Storage conditions in particular are difficult to simulate, as they are dependent on environmental conditions (e.g. intensity and dose of light, temperature, air flow, humidity) and cannot be controlled in the natural aging of questioned documents. The problem therefore lies more in the variety of different conditions a questioned document might be exposed to during its natural aging, rather than in the simulation of such conditions in the laboratory. Nevertheless, a precise modelling of natural aging curves based on artificial aging curves is obtained when performed on the same paper and ink. A standard model for aging processes of ink on paper is therefore presented that is based on a fit of aging curves to a power law of solvent concentrations as a function of time. A mathematical transformation of artificial aging curves into modelled natural aging curves results in excellent overlap with data from real natural aging processes.

Animal and human models to understand ageing.

Science.gov (United States)

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

The yeast replicative aging model.

Science.gov (United States)

He, Chong; Zhou, Chuankai; Kennedy, Brian K

2018-03-08

It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

[Active ageing and success: A brief history of conceptual models].

Science.gov (United States)

Petretto, Donatella Rita; Pili, Roberto; Gaviano, Luca; Matos López, Cristina; Zuddas, Carlo

2016-01-01

The aim of this paper is to analyse and describe different conceptual models of successful ageing, active and healthy ageing developed in Europe and in America in the 20° century, starting from Rowe and Kahn's original model (1987, 1997). A narrative review was conducted on the literature on successful ageing. Our review included definition of successful ageing from European and American scholars. Models were found that aimed to describe indexes of active and healthy ageing, models devoted to describe processes involved in successful ageing, and additional views that emphasise subjective and objective perception of successful ageing. A description is also given of critiques on previous models and remedies according to Martin et al. (2014) and strategies for successful ageing according to Jeste and Depp (2014). The need is discussed for the enhancement of Rowe and Kahn's model and other models with a more inclusive, universal description of ageing, incorporating scientific evidence regarding active ageing. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Re-evaluating neonatal-age models for ungulates: does model choice affect survival estimates?

Directory of Open Access Journals (Sweden)

Troy W Grovenburg

Full Text Available 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

A comprehensive approach to age-dependent dosimetric modeling

International Nuclear Information System (INIS)

Leggett, R.W.; Cristy, M.; Eckerman, K.F.

1986-01-01

In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks

A comprehensive approach to age-dependent dosimetric modeling

International Nuclear Information System (INIS)

Leggett, R.W.; Cristy, M.; Eckerman, K.F.

1987-01-01

In the absence of age-specific biokinetic models, current retention models of the International Commission of Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper a comprehensive approach to age-dependent dosimetric modeling is discussed in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates of risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks. 16 refs.; 3 figs.; 1 table

Modeling age-specific mortality for countries with generalized HIV epidemics.

Directory of Open Access Journals (Sweden)

David J Sharrow

Full Text Available In a given population the age pattern of mortality is an important determinant of total number of deaths, age structure, and through effects on age structure, the number of births and thereby growth. Good mortality models exist for most populations except those experiencing generalized HIV epidemics and some developing country populations. The large number of deaths concentrated at very young and adult ages in HIV-affected populations produce a unique 'humped' age pattern of mortality that is not reproduced by any existing mortality models. Both burden of disease reporting and population projection methods require age-specific mortality rates to estimate numbers of deaths and produce plausible age structures. For countries with generalized HIV epidemics these estimates should take into account the future trajectory of HIV prevalence and its effects on age-specific mortality. In this paper we present a parsimonious model of age-specific mortality for countries with generalized HIV/AIDS epidemics.The model represents a vector of age-specific mortality rates as the weighted sum of three independent age-varying components. We derive the age-varying components from a Singular Value Decomposition of the matrix of age-specific mortality rate schedules. The weights are modeled as a function of HIV prevalence and one of three possible sets of inputs: life expectancy at birth, a measure of child mortality, or child mortality with a measure of adult mortality. We calibrate the model with 320 five-year life tables for each sex from the World Population Prospects 2010 revision that come from the 40 countries of the world that have and are experiencing a generalized HIV epidemic. Cross validation shows that the model is able to outperform several existing model life table systems.We present a flexible, parsimonious model of age-specific mortality for countries with generalized HIV epidemics. Combined with the outputs of existing epidemiological and

Shared Ageing Research Models (ShARM) : a new facility to support ageing research

NARCIS (Netherlands)

Duran, Adele L.; Potter, Paul; Wells, Sara; Kirkwood, Tom; von Zglinicki, Thomas; McArdle, Anne; Scudamore, Cheryl; Meng, Qing-Jun; de Haan, Gerald; Corcoran, Anne; Bellantuono, Ilaria

2013-01-01

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing.

Stem Cell Models: A Guide to Understand and Mitigate Aging?

Science.gov (United States)

Brunauer, Regina; Alavez, Silvestre; Kennedy, Brian K

2017-01-01

Aging is studied either on a systemic level using life span and health span of animal models, or on the cellular level using replicative life span of yeast or mammalian cells. While useful in identifying general and conserved pathways of aging, both approaches provide only limited information about cell-type specific causes and mechanisms of aging. Stem cells are the regenerative units of multicellular life, and stem cell aging might be a major cause for organismal aging. Using the examples of hematopoietic stem cell aging and human pluripotent stem cell models, we propose that stem cell models of aging are valuable for studying tissue-specific causes and mechanisms of aging and can provide unique insights into the mammalian aging process that may be inaccessible in simple model organisms. © 2016 S. Karger AG, Basel.

Travelling Wave Solutions in Multigroup Age-Structured Epidemic Models

Science.gov (United States)

Ducrot, Arnaut; Magal, Pierre; Ruan, Shigui

2010-01-01

Age-structured epidemic models have been used to describe either the age of individuals or the age of infection of certain diseases and to determine how these characteristics affect the outcomes and consequences of epidemiological processes. Most results on age-structured epidemic models focus on the existence, uniqueness, and convergence to disease equilibria of solutions. In this paper we investigate the existence of travelling wave solutions in a deterministic age-structured model describing the circulation of a disease within a population of multigroups. Individuals of each group are able to move with a random walk which is modelled by the classical Fickian diffusion and are classified into two subclasses, susceptible and infective. A susceptible individual in a given group can be crisscross infected by direct contact with infective individuals of possibly any group. This process of transmission can depend upon the age of the disease of infected individuals. The goal of this paper is to provide sufficient conditions that ensure the existence of travelling wave solutions for the age-structured epidemic model. The case of two population groups is numerically investigated which applies to the crisscross transmission of feline immunodeficiency virus (FIV) and some sexual transmission diseases.

Virtual age model for equipment aging plant based on operation environment and service state

International Nuclear Information System (INIS)

Zhang Liming; Cai Qi; Zhao Xinwen; Chen Ling

2010-01-01

The accelerated life model based on the operation environment and service state was established by taking the virtual age as the equipment aging indices. The effect of different operation environments and service states on the reliability and virtual age under the continuum operation conditions and cycle operation conditions were analyzed, and the sensitivities of virtual age on operational environments and service states were studied. The results of the example application show that the effect of NPP equipment lifetime and the key parameters related to the reliability can be quantified by this model, and the result is in accordance with the reality.(authors)

An integrated modeling approach to age invariant face recognition

Science.gov (United States)

Alvi, Fahad Bashir; Pears, Russel

2015-03-01

This Research study proposes a novel method for face recognition based on Anthropometric features that make use of an integrated approach comprising of a global and personalized models. The system is aimed to at situations where lighting, illumination, and pose variations cause problems in face recognition. A Personalized model covers the individual aging patterns while a Global model captures general aging patterns in the database. We introduced a de-aging factor that de-ages each individual in the database test and training sets. We used the k nearest neighbor approach for building a personalized model and global model. Regression analysis was applied to build the models. During the test phase, we resort to voting on different features. We used FG-Net database for checking the results of our technique and achieved 65 percent Rank 1 identification rate.

Aging models of acute seizures and epilepsy.

Science.gov (United States)

Kelly, Kevin M

2010-01-01

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.

Spatial age-length key modelling using continuation ratio logits

DEFF Research Database (Denmark)

Berg, Casper W.; Kristensen, Kasper

2012-01-01

-called age-length key (ALK) is then used to obtain the age distribution. Regional differences in ALKs are not uncommon, but stratification is often problematic due to a small number of samples. Here, we combine generalized additive modelling with continuation ratio logits to model the probability of age...

Canadian government's framing of ageing at work and older workers: Echoing positive ageing models.

Science.gov (United States)

Lagacé, Martine; Nahon-Serfaty, Isaac; Laplante, Joelle

2015-01-01

Public representations of ageing can influence how individuals perceive their own experience of ageing. Results of studies on the OECD (Organisation for Economic Co-operation and Development)'s governmental messages on older workers suggest that they are mainly constructed around economic productivity and personal responsibility. The goal of this study is to examine how the Canadian government frames issues around ageing, work and older workers. Canada is facing a rapidly ageing workforce, hence the importance of examining how the government discusses ageing at work. A thematic content analysis was conducted on a total of 154 government web pages. Results revealed that predominant themes revolve around economic challenges resulting from an ageing workforce. Older workers are depicted as a key component for the (economic) management of an ageing workforce. More specifically, older workers who intend to continue working are highly valued in the government's messages which present them as productive citizens and role models for "ageing well". Canada's response to the challenges of an ageing workforce echoes the underlying standards of positive ageing models, which may generate, perhaps inadvertently, a new form of ageism by creating intra-and intergenerational divides in the workplace.

Total deposition of inhaled particles related to age: comparison with age-dependent model calculations

International Nuclear Information System (INIS)

Becquemin, M.H.; Bouchikhi, A.; Yu, C.P.; Roy, M.

1991-01-01

To compare experimental data with age-dependent model calculations, total airway deposition of polystyrene aerosols (1, 2.05 and 2.8 μm aerodynamic diameter) was measured in ten adults, twenty children aged 12 to 15 years, ten children aged 8 to 12, and eleven under 8 years old. Ventilation was controlled, and breathing patterns were appropriate for each age, either at rest or at light exercise. Individually, deposition percentages increased with particle size and also from rest to exercise, except in children under 12 years, in whom they decreased from 20-21.5 to 14-14.5 for 1 μm particles and from 36.8-36.9 to 32.2-33.1 for 2.05 μm particles. Comparisons with the age-dependent model showed that, at rest, the observed data concerning children agreed with those predicted and were close to the adults' values, when the latter were higher than predicted. At exercise, child data were lower than predicted and lower than adult experimental data, when the latter agreed fairly well with the model. (author)

An age structured model for obesity prevalence dynamics in populations

Directory of Open Access Journals (Sweden)

Gilberto González Parra

2010-08-01

Full Text Available Objective. Modeling the correlation of the development of obesity in a population with age and time and predict the dynamics of the correlation of the development of obesity in a population with age and time under different scenarios in Valencia (Spain. Materials and methods. An age structured mathematical model is used to describe the future dynamics of obesity prevalence for different ages in human population with excess weight. Simulation of the model with parameters estimated using the Health Survey of the Region of Valencia 2000 (4.319 interviews and Health Survey of the Region of Valencia 2005 (4.012 interviews. The model considers only overweight and obese populations since these subpopulations are the most relevant on obesity health concern. Results. The model allows predicting and studying the prevalence of obesity for each age. Results showed an increasing trend of obesity in the following years in well accordance with the trend observed in several countries. Conclusions. Based on the numerical simulations it is possible to conclude that the age structured mathematical model is suitable to forecast the obesity epidemic in each age group in different countries. Additionally, this type of models may be applied to study other characteristics of other populations such animal populations.

Practical problems of groundwater model ages for groundwater protection studies

International Nuclear Information System (INIS)

Matthess, G.; Muennich, K.O.; Sonntag, C.

1976-01-01

Water authorities in the Federal Republic of Germany have established a system of protection zones for the protection of groundwater supplies from pollution. One zone (Zone II) is defined by an outer boundary from which the groundwater needs 50 days to flow to the well. 50 days is the period accepted for the elimination of pathogenic germs. However, within Zone II carbon-14 measurements of water may give model ages of several thousand years, which may lead to some confusion in the legal and practical aspects of this scheme. These model ages may result from uncertainties in the chemical model, or from mixing of waters of different ages, either within the aquifer or during extraction at the well. The paper discusses scientific aspects of the establishment of protection zones. Two processes affecting the model age determinations are examined in detail. First, the mechanism of diffusion transport downwards through porous, but impermeable, aquicludes is examined for stable trace substances and radioactive isotopes. Secondly, examples are given of model ages resulting from mixtures of new and old waters. It is recommended that such model ages should not be reported as 'ages' since they may be misinterpreted in groundwater protection applications. (author)

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study.

Science.gov (United States)

Bélanger, Emmanuelle; Ahmed, Tamer; Filiatrault, Johanne; Yu, Hsiu-Ting; Zunzunegui, Maria Victoria

2017-04-01

Active aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada. The WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario. Neither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO. Our results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Degradation modeling with application to aging and maintenance effectiveness evaluations

International Nuclear Information System (INIS)

Samanta, P.K.; Hsu, F.; Subduhi, M.; Vesely, W.E.

1990-01-01

This paper describes a modeling approach to analyze component degradation and failure data to understand the aging process of components. As used here, degradation modeling is the analysis of information on component degradation in order to develop models of the process and its implications. This particular modeling focuses on the analysis of the times of component degradations, to model how the rate of degradation changes with the age of the component. The methodology presented also discusses the effectiveness of maintenance as applicable to aging evaluations. The specific applications which are performed show quantitative models of component degradation rates and component failure rates from plant-specific data. The statistical techniques which are developed and applied allow aging trends to be effectively identified in the degradation data, and in the failure data. Initial estimates of the effectiveness of maintenance in limiting degradations from becoming failures also are developed. These results are important first steps in degradation modeling, and show that degradation can be modeled to identify aging trends. 2 refs., 8 figs

Degradation modeling with application to aging and maintenance effectiveness evaluations

International Nuclear Information System (INIS)

Samanta, P.K.; Vesely, W.E.; Hsu, F.; Subudhi, M.

1991-01-01

This paper describes a modeling approach to analyze light water reactor component degradation and failure data to understand the aging process of components. As used here, degradation modeling is the analysis of information on component degradation in order to develop models of the process and its implications. This particular modeling focuses on the analysis of the times of component degradations, to model how the rate of degradation changes with the age of the component. The methodology presented also discusses the effectiveness of maintenance as applicable to aging evaluations. The specific applications which are performed show quantitative models of component degradation rates and component failure rates from plant-specific data. The statistical techniques which are developed and applied allow aging trends to be effectively identified in the degradation data, and in the failure data. Initial estimates of the effectiveness of maintenance in limiting degradations from becoming failures also are developed. These results are important first steps in degradation modeling, and show that degradation can be modeled to identify aging trends

Age-dependent metabolic model of radionuclides in Human body

International Nuclear Information System (INIS)

Ye Changqing

1986-01-01

Age-dependent metabolic model of radionuclides in human body was introduced briefly. These data are necessary in setting up the secondary dose limit of internal exposure of the general public. For the gastro-intestinal tract model, it was shown that the dose of various sections of GI tract caused by unsoluble radioactive materials were influenced by the mass of section and mean residence time, both of which are age-dependent, but the absorption fraction f 1 through gastro-intestinal tract should be corrected only for the infant less than 1 year of age. For the lung model, it was indicated that the fraction of deposition or clearance of particles in the different compartments of lung were related to age. The doses of tracheobronchial and pulmonary compartment of adult for 222 Rn or 220 Rn with their decay products were one third of that of 6-years old child who received the maximum dose in comparison with other ages. The age-dependent metabolic models in organ and/or body of Tritium, Iodine-131, Caesium-137, radioactive Strontium, Radium and Plutonium were reported. A generalized approach for estimating the effect of age on deposition fractions and retention half-time were presented. Calculated results indicated that younger ages were characterized by increased deposition fraction and decreased half-time for retention. Representative examples were provided for 21 elements of current interest in health physics

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.

Pathology of Mouse Models of Accelerated Aging

NARCIS (Netherlands)

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

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,

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,"

Animal models of age related macular degeneration

Science.gov (United States)

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

2013-01-01

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 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. PMID:22705444

Radiocarbon ages and age models for the past 30,000 years in Bear Lake, Utah and Idaho

Science.gov (United States)

Colman, Steven M.; Rosenbaum, J.G.; Kaufman, D.S.; Dean, W.E.; McGeehin, J.P.

2009-01-01

Radiocarbon analyses of pollen, ostracodes, and total organic carbon (TOC) provide a reliable chronology for the sediments deposited in Bear Lake over the past 30,000 years. The differences in apparent age between TOC, pollen, and carbonate fractions are consistent and in accord with the origins of these fractions. Comparisons among different fractions indicate that pollen sample ages are the most reliable, at least for the past 15,000 years. The post-glacial radiocarbon data also agree with ages independently estimated from aspartic acid racemization in ostracodes. Ages in the red, siliclastic unit, inferred to be of last glacial age, appear to be several thousand years too old, probably because of a high proportion of reworked, refractory organic carbon in the pollen samples. Age-depth models for five piston cores and the Bear Lake drill core (BL00-1) were constructed by using two methods: quadratic equations and smooth cubic-splinefits. The two types of age models differ only in detail for individual cores, and each approach has its own advantages. Specific lithological horizons were dated in several cores and correlated among them, producing robust average ages for these horizons. The age of the correlated horizons in the red, siliclastic unit can be estimated from the age model for BL00-1, which is controlled by ages above and below the red, siliclastic unit. These ages were then transferred to the correlative horizons in the shorter piston cores, providing control for the sections of the age models in those cores in the red, siliclastic unit. These age models are the backbone for reconstructions of past environmental conditions in Bear Lake. In general, sedimentation rates in Bear Lake have been quite uniform, mostly between 0.3 and 0.8 mm yr-1 in the Holocene, and close to 0.5 mm yr-1 for the longer sedimentary record in the drill core from the deepest part of the lake. Copyright ?? 2009 The Geological Society of America.

Age-depth modelling with radiocarbon

International Nuclear Information System (INIS)

Howarth, J.D.

2017-01-01

Chronology is a critical component of any study into the Quaternary because the information about climate and environmental change preserved in sedimentary deposits can only be placed in a useful context when it is associated with a robust chronological framework. This overview will introduce you to the key concepts in age depth modelling.

Age- and sex-specific thorax finite element model development and simulation.

Science.gov (United States)

Schoell, Samantha L; Weaver, Ashley A; Vavalle, Nicholas A; Stitzel, Joel D

2015-01-01

The shape, size, bone density, and cortical thickness of the thoracic skeleton vary significantly with age and sex, which can affect the injury tolerance, especially in at-risk populations such as the elderly. Computational modeling has emerged as a powerful and versatile tool to assess injury risk. However, current computational models only represent certain ages and sexes in the population. The purpose of this study was to morph an existing finite element (FE) model of the thorax to depict thorax morphology for males and females of ages 30 and 70 years old (YO) and to investigate the effect on injury risk. Age- and sex-specific FE models were developed using thin-plate spline interpolation. In order to execute the thin-plate spline interpolation, homologous landmarks on the reference, target, and FE model are required. An image segmentation and registration algorithm was used to collect homologous rib and sternum landmark data from males and females aged 0-100 years. The Generalized Procrustes Analysis was applied to the homologous landmark data to quantify age- and sex-specific isolated shape changes in the thorax. The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant model was morphed to create age- and sex-specific thoracic shape change models (scaled to a 50th percentile male size). To evaluate the thoracic response, 2 loading cases (frontal hub impact and lateral impact) were simulated to assess the importance of geometric and material property changes with age and sex. Due to the geometric and material property changes with age and sex, there were observed differences in the response of the thorax in both the frontal and lateral impacts. Material property changes alone had little to no effect on the maximum thoracic force or the maximum percent compression. With age, the thorax becomes stiffer due to superior rotation of the ribs, which can result in increased bone strain that can increase the risk of fracture. For the 70-YO models

An artificial intelligence tool for complex age-depth models

Science.gov (United States)

Bradley, E.; Anderson, K. A.; de Vesine, L. R.; Lai, V.; Thomas, M.; Nelson, T. H.; Weiss, I.; White, J. W. C.

2017-12-01

CSciBox is an integrated software system for age modeling of paleoenvironmental records. It incorporates an array of data-processing and visualization facilities, ranging from 14C calibrations to sophisticated interpolation tools. Using CSciBox's GUI, a scientist can build custom analysis pipelines by composing these built-in components or adding new ones. Alternatively, she can employ CSciBox's automated reasoning engine, Hobbes, which uses AI techniques to perform an in-depth, autonomous exploration of the space of possible age-depth models and presents the results—both the models and the reasoning that was used in constructing and evaluating them—to the user for her inspection. Hobbes accomplishes this using a rulebase that captures the knowledge of expert geoscientists, which was collected over the course of more than 100 hours of interviews. It works by using these rules to generate arguments for and against different age-depth model choices for a given core. Given a marine-sediment record containing uncalibrated 14C dates, for instance, Hobbes tries CALIB-style calibrations using a choice of IntCal curves, with reservoir age correction values chosen from the 14CHRONO database using the lat/long information provided with the core, and finally composes the resulting age points into a full age model using different interpolation methods. It evaluates each model—e.g., looking for outliers or reversals—and uses that information to guide the next steps of its exploration, and presents the results to the user in human-readable form. The most powerful of CSciBox's built-in interpolation methods is BACON, a Bayesian sedimentation-rate algorithm—a powerful but complex tool that can be difficult to use. Hobbes adjusts BACON's many parameters autonomously to match the age model to the expectations of expert geoscientists, as captured in its rulebase. It then checks the model against the data and iteratively re-calculates until it is a good fit to the data.

Mouse models of ageing and their relevance to disease.

Science.gov (United States)

Kõks, Sulev; Dogan, Soner; Tuna, Bilge Guvenc; González-Navarro, Herminia; Potter, Paul; Vandenbroucke, Roosmarijn E

2016-12-01

Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility. In addition to addressing the genetics and phenotypic analysis of mice, we discuss examples of models of delayed or accelerated ageing and their modulation by caloric restriction. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

MOD-AGE - an algorithm for age-depth model construction; U-series dated speleothems case study

Science.gov (United States)

Hercman, H.; Pawlak, J.

2012-04-01

We present MOD-AGE - a new system for chronology construction. MOD-AGE can be used for profiles that have been dated by different methods. As input data, the system uses the following basic measurements: activities, atomic ratios or age, as well as depth measurement. Based on probability distributions describing the measurement results, MOD-AGE estimates the age~depth relation and its confidence bands. To avoid the use of difficult-to-meet assumptions, MOD-AGE uses nonparametric methods. We applied a Monte Carlo simulation to model age and depth values based on the real distribution of counted data (activities, atomic ratios, depths etc.). Several fitting methods could be applied for estimating the relationships; based on several tests, we decide to use LOESS method (locally weighted scatterplot smoothing). The stratigraphic correction procedure applied in the MOD-AGE program uses a probability calculus, which assumes that the ages of all the samples are correctly estimated. Information about the probability distribution of the samples' ages is used to estimate the most probable sequence that is concordant according to the superposition rule. MOD-AGE is presented as a tool for the chronology construction of speleothems that have been analyzed by the U-series method, and it is compared to the StalAge algorithm presented by D. Scholtz and D.L Hoffmann (2011). Scholtz, D., Hoffmann, D. L., 2011. StalAge - An algorithm designed for construction of speleothem age models. Quaternary Geochronology 6, 369-382.

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.

Stability analysis for a general age-dependent vaccination model

International Nuclear Information System (INIS)

El Doma, M.

1995-05-01

An SIR epidemic model of a general age-dependent vaccination model is investigated when the fertility, mortality and removal rates depends on age. We give threshold criteria of the existence of equilibriums and perform stability analysis. Furthermore a critical vaccination coverage that is sufficient to eradicate the disease is determined. (author). 12 refs

An age dependent model for radium metabolism in man.

Science.gov (United States)

Johnson, J R

1983-01-01

The model developed by a Task Group of Committee 2 of ICRP to describe Alkaline Earth Metabolism in Adult Man (ICRP Publication 20) has been modified so that recycling is handled explicitly, and retention in mineral bone is represented by second compartments rather than by the product of a power function and an exponential. This model has been extended to include all ages from birth to adult man, and has been coupled with modified "ICRP" lung and G.I. tract models so that activity in organs can be calculated as functions of time during or after exposures. These activities, and age dependent "specific effective energy" factors, are then used to calculate age dependent dose rates, and dose commitments. This presentation describes this work, with emphasis on the model parameters and results obtained for radium.

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.

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

International Nuclear Information System (INIS)

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.

2005-01-01

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

An evaluation of sex-age-kill (SAK) model performance

Science.gov (United States)

Millspaugh, Joshua J.; Skalski, John R.; Townsend, Richard L.; Diefenbach, Duane R.; Boyce, Mark S.; Hansen, Lonnie P.; Kammermeyer, Kent

2009-01-01

The sex-age-kill (SAK) model is widely used to estimate abundance of harvested large mammals, including white-tailed deer (Odocoileus virginianus). Despite a long history of use, few formal evaluations of SAK performance exist. We investigated how violations of the stable age distribution and stationary population assumption, changes to male or female harvest, stochastic effects (i.e., random fluctuations in recruitment and survival), and sampling efforts influenced SAK estimation. When the simulated population had a stable age distribution and λ > 1, the SAK model underestimated abundance. Conversely, when λ < 1, the SAK overestimated abundance. When changes to male harvest were introduced, SAK estimates were opposite the true population trend. In contrast, SAK estimates were robust to changes in female harvest rates. Stochastic effects caused SAK estimates to fluctuate about their equilibrium abundance, but the effect dampened as the size of the surveyed population increased. When we considered both stochastic effects and sampling error at a deer management unit scale the resultant abundance estimates were within ±121.9% of the true population level 95% of the time. These combined results demonstrate extreme sensitivity to model violations and scale of analysis. Without changes to model formulation, the SAK model will be biased when λ ≠ 1. Furthermore, any factor that alters the male harvest rate, such as changes to regulations or changes in hunter attitudes, will bias population estimates. Sex-age-kill estimates may be precise at large spatial scales, such as the state level, but less so at the individual management unit level. Alternative models, such as statistical age-at-harvest models, which require similar data types, might allow for more robust, broad-scale demographic assessments.

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

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. (c) 2015 APA, all rights reserved).

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.

The heuristic value of redundancy models of aging

NARCIS (Netherlands)

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

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.

The short-lived African turquoise killifish: an emerging experimental model for ageing.

Science.gov (United States)

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-02-01

Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. © 2016. Published by The Company of Biologists Ltd.

Age dependent mortality in the pilocarpine model of status epilepticus

Science.gov (United States)

Blair, Robert E.; Deshpande, Laxmikant S.; Holbert, William H.; Churn, Severn B.; DeLorenzo, Robert J.

2010-01-01

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death. PMID:19429042

Age-dependent mortality in the pilocarpine model of status epilepticus.

Science.gov (United States)

Blair, Robert E; Deshpande, Laxmikant S; Holbert, William H; Churn, Severn B; DeLorenzo, Robert J

2009-04-10

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 and 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week-old animals, mortality due to SE increased progressively with age and reached 90% in 28-week-old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.

An age-structured extension to the vectorial capacity model.

Directory of Open Access Journals (Sweden)

Vasiliy N Novoseltsev

Full Text Available 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.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.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-dependent mortality models is the paucity of data characterizing vector mortality

Novel polyglutamine model uncouples proteotoxicity from aging.

Science.gov (United States)

Christie, Nakeirah T M; Lee, Amy L; Fay, Hannah G; Gray, Amelia A; Kikis, Elise A

2014-01-01

Polyglutamine expansions in certain proteins are the genetic determinants for nine distinct progressive neurodegenerative disorders and resultant age-related dementia. In these cases, neurodegeneration is due to the aggregation propensity and resultant toxic properties of the polyglutamine-containing proteins. We are interested in elucidating the underlying mechanisms of toxicity of the protein ataxin-3, in which a polyglutamine expansion is the genetic determinant for Machado-Joseph Disease (MJD), also referred to as spinocerebellar ataxia 3 (SCA3). To this end, we have developed a novel model for ataxin-3 protein aggregation, by expressing a disease-related polyglutamine-containing fragment of ataxin-3 in the genetically tractable body wall muscle cells of the model system C. elegans. Here, we demonstrate that this ataxin-3 fragment aggregates in a polyQ length-dependent manner in C. elegans muscle cells and that this aggregation is associated with cellular dysfunction. However, surprisingly, this aggregation and resultant toxicity was not influenced by aging. This is in contrast to polyglutamine peptides alone whose aggregation/toxicity is highly dependent on age. Thus, the data presented here not only describe a new polyglutamine model, but also suggest that protein context likely influences the cellular interactions of the polyglutamine-containing protein and thereby modulates its toxic properties.

Novel polyglutamine model uncouples proteotoxicity from aging.

Directory of Open Access Journals (Sweden)

Nakeirah T M Christie

Full Text Available Polyglutamine expansions in certain proteins are the genetic determinants for nine distinct progressive neurodegenerative disorders and resultant age-related dementia. In these cases, neurodegeneration is due to the aggregation propensity and resultant toxic properties of the polyglutamine-containing proteins. We are interested in elucidating the underlying mechanisms of toxicity of the protein ataxin-3, in which a polyglutamine expansion is the genetic determinant for Machado-Joseph Disease (MJD, also referred to as spinocerebellar ataxia 3 (SCA3. To this end, we have developed a novel model for ataxin-3 protein aggregation, by expressing a disease-related polyglutamine-containing fragment of ataxin-3 in the genetically tractable body wall muscle cells of the model system C. elegans. Here, we demonstrate that this ataxin-3 fragment aggregates in a polyQ length-dependent manner in C. elegans muscle cells and that this aggregation is associated with cellular dysfunction. However, surprisingly, this aggregation and resultant toxicity was not influenced by aging. This is in contrast to polyglutamine peptides alone whose aggregation/toxicity is highly dependent on age. Thus, the data presented here not only describe a new polyglutamine model, but also suggest that protein context likely influences the cellular interactions of the polyglutamine-containing protein and thereby modulates its toxic properties.

A living model for obesity and aging research: Caenorhabditis elegans.

Science.gov (United States)

Shen, Peiyi; Yue, Yiren; Park, Yeonhwa

2018-03-24

Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for research involving aging and neurodegenerative diseases, like Alzheimer's and Parkinson's, etc. Compared with traditional animal models, this small nematode possesses many benefits, such as small body size, short lifespan, completely sequenced genome, and more than 65% of the genes associated with human disease. All these characteristics make this organism an ideal living system for obesity and aging studies. This review gives a brief introduction of C. elegans as an animal model, highlights some advantages of research using this model and describes methods to evaluate the effect of treatments on obesity and aging of this organism.

An agent-based computational model for tuberculosis spreading on age-structured populations

Science.gov (United States)

Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

2015-06-01

In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

Lattice Modeling of Early-Age Behavior of Structural Concrete

OpenAIRE

Pan, Yaming; Prado, Armando; Porras, Roc?o; Hafez, Omar M.; Bolander, John E.

2017-01-01

The susceptibility of structural concrete to early-age cracking depends on material composition, methods of processing, structural boundary conditions, and a variety of environmental factors. Computational modeling offers a means for identifying primary factors and strategies for reducing cracking potential. Herein, lattice models are shown to be adept at simulating the thermal-hygral-mechanical phenomena that influence early-age cracking. In particular, this paper presents a lattice-based ap...

An Age-Structured Extension to the Vectorial Capacity Model

Science.gov (United States)

Novoseltsev, Vasiliy N.; Michalski, Anatoli I.; Novoseltseva, Janna A.; Yashin, Anatoliy I.; Carey, James R.; Ellis, Alicia M.

2012-01-01

Background Vectorial capacity and the basic reproductive number (R0) 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 R0 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 R0 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 R0 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 R0∼1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the

Optimization of arterial age prediction models based in pulse wave

Energy Technology Data Exchange (ETDEWEB)

Scandurra, A G [Bioengineering Laboratory, Electronic Department, Mar del Plata University (Argentina); Meschino, G J [Bioengineering Laboratory, Electronic Department, Mar del Plata University (Argentina); Passoni, L I [Bioengineering Laboratory, Electronic Department, Mar del Plata University (Argentina); Dai Pra, A L [Engineering Aplied Artificial Intelligence Group, Mathematics Department, Mar del Plata University (Argentina); Introzzi, A R [Bioengineering Laboratory, Electronic Department, Mar del Plata University (Argentina); Clara, F M [Bioengineering Laboratory, Electronic Department, Mar del Plata University (Argentina)

2007-11-15

We propose the detection of early arterial ageing through a prediction model of arterial age based in the coherence assumption between the pulse wave morphology and the patient's chronological age. Whereas we evaluate several methods, a Sugeno fuzzy inference system is selected. Models optimization is approached using hybrid methods: parameter adaptation with Artificial Neural Networks and Genetic Algorithms. Features selection was performed according with their projection on main factors of the Principal Components Analysis. The model performance was tested using the bootstrap error type .632E. The model presented an error smaller than 8.5%. This result encourages including this process as a diagnosis module into the device for pulse analysis that has been developed by the Bioengineering Laboratory staff.

Optimization of arterial age prediction models based in pulse wave

International Nuclear Information System (INIS)

Scandurra, A G; Meschino, G J; Passoni, L I; Dai Pra, A L; Introzzi, A R; Clara, F M

2007-01-01

We propose the detection of early arterial ageing through a prediction model of arterial age based in the coherence assumption between the pulse wave morphology and the patient's chronological age. Whereas we evaluate several methods, a Sugeno fuzzy inference system is selected. Models optimization is approached using hybrid methods: parameter adaptation with Artificial Neural Networks and Genetic Algorithms. Features selection was performed according with their projection on main factors of the Principal Components Analysis. The model performance was tested using the bootstrap error type .632E. The model presented an error smaller than 8.5%. This result encourages including this process as a diagnosis module into the device for pulse analysis that has been developed by the Bioengineering Laboratory staff

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.

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.

Ageing of palladium tritide: mechanical characterization, helium state and modelling

International Nuclear Information System (INIS)

Segard, M.

2010-01-01

Palladium is commonly used for the storage of tritium (the hydrogen radioactive isotope), since it forms a low-equilibrium-pressure and reversible tritide. Tritium decay into helium-3 is responsible for the ageing of the tritide, leading to the apparition of helium-3 bubbles for instance. Both experimental and theoretical aspects of this phenomenon are studied here.Previous works on ageing modelling led to two main models, dealing with:- Helium-3 bubbles nucleation (using a cellular automaton), - Bubbles growth (using continuum mechanics).These models were quite efficient, but their use was limited by the lack of input data and fitting experimental parameters.To get through these limitations, this work has consisted in studying the most relevant experimental data to improve the modelling of the palladium tritide ageing.The first part of this work was focused on the assessment of the mechanical properties of the palladium tritide (yield strength, ultimate strength, mechanical behaviour). They were deduced from the in situ tensile tests performed on palladium hydride and deuteride. In the second part, ageing characterization was undertaken, mainly focusing on: - Bubbles observations in palladium tritide using transmission electron microscopy, - Internal bubble pressure measurements using nuclear magnetic resonance, - Macroscopic swelling measurements using pycno-metry.The present work has led to significant progress in ageing understanding and has brought very valuable improvements to the modelling of such a phenomenon. (author) [fr

Are invertebrates relevant models in ageing research?

DEFF Research Database (Denmark)

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

2016-01-01

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...

Developing a dimensional model for successful cognitive and emotional aging.

Science.gov (United States)

Vahia, Ipsit V; Thompson, Wesley K; Depp, Colin A; Allison, Matthew; Jeste, Dilip V

2012-04-01

There is currently a lack of consensus on the definition of successful aging (SA) and existing implementations have omitted constructs associated with SA. We used empirical methods to develop a dimensional model of SA that incorporates a wider range of associated variables, and we examined the relationship among these components using factor analysis and Bayesian Belief Nets. We administered a successful aging questionnaire comprising several standardized measures related to SA to a sample of 1948 older women enrolled in the San Diego site of the Women's Health Initiative study. The SA-related variables we included in the model were self-rated successful aging, depression severity, physical and emotional functioning, optimism, resilience, attitude towards own aging, self-efficacy, and cognitive ability. After adjusting for age, education and income, we fitted an exploratory factor analysis model to the SA-related variables and then, in order to address relationships among these factors, we computed a Bayesian Belief Net (BBN) using rotated factor scores. The SA-related variables loaded onto five factors. Based on the loading, we labeled the factors as follows: self-rated successful aging, cognition, psychosocial protective factors, physical functioning, and emotional functioning. In the BBN, self-rated successful aging emerged as the primary downstream factor and exhibited significant partial correlations with psychosocial protective factors, physical/general status and mental/emotional status but not with cognitive ability. Our study represents a step forward in developing a dimensional model of SA. Our findings also point to a potential role for psychiatry in improving successful aging by managing depressive symptoms and developing psychosocial interventions to improve self-efficacy, resilience, and optimism.

Computer modelling of age hardening for cast aluminium alloys

International Nuclear Information System (INIS)

Wu, Linda; Ferguson, W George

2009-01-01

Age hardening, or precipitation hardening, is one of the most widely adopted techniques for strengthening of aluminium alloys. Although various age hardening models have been developed for aluminium alloys, from the large volume of literature reviewed, it appears that the bulk of the research has been concentrated on wrought aluminium alloys, only a few of the established precipitation models have been applied to the casting aluminium alloys. In the present work, there are two modelling methods that have been developed and applied to the casting aluminium alloys A356 and A357. One is based on the Shercliff-Ashby methodology to produce a process model, by which we mean a mathematical relationship between process variables (alloy composition, ageing temperature and time) and material properties (yield strength or hardness) through microstructure evolution (precipitate radius, volume fraction). The other method is based on the Kampmann and Wagner Numerical (KWN) model which deals with concomitant nucleation, growth and coarsening and is thus capable of predicting the full evolution of the particle size distribution and then a strength model is used to evaluate the resulting change in hardness or yield strength at room temperature by taking into account contributions from lattice resistance, solid solution hardening and precipitation hardening.

Component Degradation Susceptibilities As The Bases For Modeling Reactor Aging Risk

International Nuclear Information System (INIS)

Unwin, Stephen D.; Lowry, Peter P.; Toyooka, Michael Y.

2010-01-01

The extension of nuclear power plant operating licenses beyond 60 years in the United States will be necessary if we are to meet national energy needs while addressing the issues of carbon and climate. Characterizing the operating risks associated with aging reactors is problematic because the principal tool for risk-informed decision-making, Probabilistic Risk Assessment (PRA), is not ideally-suited to addressing aging systems. The components most likely to drive risk in an aging reactor - the passives - receive limited treatment in PRA, and furthermore, standard PRA methods are based on the assumption of stationary failure rates: a condition unlikely to be met in an aging system. A critical barrier to modeling passives aging on the wide scale required for a PRA is that there is seldom sufficient field data to populate parametric failure models, and nor is there the availability of practical physics models to predict out-year component reliability. The methodology described here circumvents some of these data and modeling needs by using materials degradation metrics, integrated with conventional PRA models, to produce risk importance measures for specific aging mechanisms and component types. We suggest that these measures have multiple applications, from the risk-screening of components to the prioritization of materials research.

Can polymer thermal oxidative ageing be modelled?

International Nuclear Information System (INIS)

Audouin, L.; Colin, X.; Fayolle, B.; Richaud, E.; Verdu, J.

2010-01-01

It has been supposed, for a long time, that kinetic modelling of polymer ageing for nonempirical lifetime prediction was out of reach for two main reasons: hyper-complexity of mechanisms and heterogeneity of reactions. The arguments relative to both aspects are examined here. It is concluded that, thanks to recent advances, especially the introduction of numerical methods, kinetic modelling is possible in various important practical cases. (authors)

Ageing model considering effects of maintenance and working conditions

International Nuclear Information System (INIS)

Martorell, S.; Sanchez, A.; Serradell, V.

1998-01-01

Nowadays, there is some doubt about building new Nuclear Power Plants (NPPs). Instead, there is a growing interest in analyzing the possibility to extend current NPP operation where life management programs play an important role. The evolution of the NPP safety depends on the evolution of the reliability of its safety components as a function of their age along the NPP operational life. In this paper, a new age-dependent reliability model is presented, which includes parameters related to surveillance and maintenance effectiveness and working conditions, both environmental and operational, of the equipment. This model may be used to support NPP life management and life extension programs by improving or optimizing surveillance and maintenance tasks using risk and cost models based on such an age-dependent reliability model. The results of the sensitivity study in the application show that the selection of the most appropriate maintenance strategy would directly depend on the previous parameters and very important differences are expected to appear under certain circumstance. (Author) 7 refs

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

Science.gov (United States)

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

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.

Aging, neurogenesis, and caloric restriction in different model organisms.

Science.gov (United States)

Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

2013-08-01

Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

Statistical models for thermal ageing of steel materials in nuclear power plants

International Nuclear Information System (INIS)

Persoz, M.

1996-01-01

Some category of steel materials in nuclear power plants may be subjected to thermal ageing, whose extent depends on the steel chemical composition and the ageing parameters, i.e. temperature and duration. This ageing affects the 'impact strength' of the materials, which is a mechanical property. In order to assess the residual lifetime of these components, a probabilistic study has been launched, which takes into account the scatter over the input parameters of the mechanical model. Predictive formulae for estimating the impact strength of aged materials are important input data of the model. A data base has been created with impact strength results obtained from an ageing program in laboratory and statistical treatments have been undertaken. Two kinds of model have been developed, with non linear regression methods (PROC NLIN, available in SAS/STAT). The first one, using a hyperbolic tangent function, is partly based on physical considerations, and the second one, of an exponential type, is purely statistically built. The difficulties consist in selecting the significant parameters and attributing initial values to the coefficients, which is a requirement of the NLIN procedure. This global statistical analysis has led to general models that are unction of the chemical variables and the ageing parameters. These models are as precise (if not more) as local models that had been developed earlier for some specific values of ageing temperature and ageing duration. This paper describes the data and the methodology used to build the models and analyses the results given by the SAS system. (author)

Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

DEFF Research Database (Denmark)

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

2012-01-01

increases the amount of unrepaired DNA damage. Despite this vicious circle, we ask, can cells maintain a high DNA repair capacity for some time or is repair capacity bound to continuously decline with age? We here present a simple mathematical model for ageing in multicellular systems where cells subjected...... 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......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...

Age dependencies in the modelling of radiation carcinogenesis

International Nuclear Information System (INIS)

Kellerer, A.M.; GSF, Neuherberg; Barclay, D.

1992-01-01

Models for the dose and age dependence of radiation induced cancer have been based primarily on the follow-up of the atomic bomb survivors. Two different concepts have been deduced for leukaemias and for other cancers. The excess leukaemias appear in a distinct temporal wave with a maximum 5 to 10 years after radiation exposure; the distribution is more narrow for younger ages, but there is little dependence of the total attributable risk on age at exposure. For other cancers the latent periods are longer and, according to the current interpretation, the excess rates are then proportional to the age specific spontaneous rates, so that most excess cases would arise at old age. The factors of proportionality, and thus the attributable risks, are assumed to be markedly higher for young ages at exposure. It is argued here, that there is no firm support for this interpretation. (author)

Investigating immune system aging: system dynamics and agent-based modeling

OpenAIRE

Figueredo, Grazziela; Aickelin, Uwe

2010-01-01

System dynamics and agent based simulation models can\\ud both be used to model and understand interactions of entities within a population. Our modeling work presented here is concerned with understanding the suitability of the different types of simulation for the immune system aging problems and comparing their results. We are trying to answer questions such as: How fit is the immune system given a certain age? Would an immune boost be of therapeutic value, e.g. to improve the effectiveness...

Risk assessment model for development of advanced age-related macular degeneration.

Science.gov (United States)

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

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

Why is the dog an ideal model for aging research?

Science.gov (United States)

Gilmore, Keiva M; Greer, Kimberly A

2015-11-01

With many caveats to the traditional vertebrate species pertaining to biogerontology investigations, it has been suggested that a most informative model is the one which: 1) examines closely related species, or various members of the same species with naturally occurring lifespan variation, 2) already has adequate medical procedures developed, 3) has a well annotated genome, 4) does not require artificial housing, and can live in its natural environment while being investigated, and 5) allows considerable information to be gathered within a relatively short period of time. The domestic dog unsurprisingly fits each criterion mentioned. The dog has already become a key model system in which to evaluate surgical techniques and novel medications because of the remarkable similarity between human and canine conditions, treatments, and response to therapy. The dog naturally serves as a disease model for study, obviating the need to construct artificial genetically modified examples of disease. Just as the dog offers a natural model for human conditions and diseases, simple observation leads to the conclusion that the canine aging phenotype also mimics that of the human. Genotype information, biochemical information pertaining to the GH/IGF-1 pathway, and some limited longitudinal investigations have begun the establishment of the domestic dog as a model of aging. Although we find that dogs indeed are a model to study aging and there are many independent pieces of canine aging data, there are many more "open" areas, ripe for investigation. Published by Elsevier Inc.

Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

Science.gov (United States)

Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

2017-05-31

Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

Evolutive masing model, cyclic plasticity, ageing and memory effects

International Nuclear Information System (INIS)

Sidoroff, F.

1987-01-01

Many models are proposed for the mechanical description of the cyclic behaviour of metals and used for structure analysis under cyclic loading. Such a model must include two basic features: Dissipative behaviour on each cycle (hysteresis loop); evolution of this behaviour during the material's life (cyclic hardening or softening, aging,...). However, if both aspects are present in most existing models, the balance between them may be quite different. Many metallurgical investigations have been performed about the microstructure and its evolution during cyclic loading, and it is desirable to introduce these informations in phenomenological models. The evolutive Masing model has been proposed to combine: the accuracy of hereditary models for the description of hysteresis on each cycle, the versatility of internal variables for the state description and evolution, a sufficient microstructural basis to make the interaction easier with microstructural investigations. The purpose of the present work is to discuss this model and to compare different evolution assumptions with respect to some memory effects (cyclic hardening and softening, multilevel tests, aging). Attention is limited to uniaxial, rate independent elasto-plastic behaviour

Ages and transit times as important diagnostics of model performance for predicting carbon dynamics in terrestrial vegetation models

Science.gov (United States)

Ceballos-Núñez, Verónika; Richardson, Andrew D.; Sierra, Carlos A.

2018-03-01

The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. These dynamics, as well as processes such as the mixing of old and newly fixed carbon, have been studied using ecosystem models, but different assumptions regarding the carbon allocation strategies and other model structures may result in highly divergent model predictions. We assessed the influence of three different carbon allocation schemes on the C cycling in vegetation. First, we described each model with a set of ordinary differential equations. Second, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find suitable parameters for the different model structures. And third, we calculated C stocks, release fluxes, radiocarbon values (based on the bomb spike), ages, and transit times. We obtained model simulations in accordance with the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed, and reduce model equifinality. Although the simulated C stocks in ecosystem compartments were similar, the different model structures resulted in very different predictions of age and transit time distributions. In particular, the inclusion of two storage compartments resulted in the prediction of a system mean age that was 12-20 years older than in the models with one or no storage compartments. The age of carbon in the wood compartment of this model was also distributed towards older ages, whereas fast cycling compartments had an age distribution that did not exceed 5 years. As expected, models with C distributed towards older ages also had longer transit times. These results suggest that ages and transit times, which can be indirectly measured using isotope tracers, serve as important diagnostics of model structure

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.

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

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.

[Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

Science.gov (United States)

Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

2010-01-01

The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

Drug repurposing for aging research using model organisms.

Science.gov (United States)

Ziehm, Matthias; Kaur, Satwant; Ivanov, Dobril K; Ballester, Pedro J; Marcus, David; Partridge, Linda; Thornton, Janet M

2017-10-01

Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila. Our approach combines information on genetic effects on aging, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate aging. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating aging, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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...

Integrated Age-based Krill Model Fish Res 2015

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — An integrated, age-structured model was fitted to different combinations of survey data using two forms of selectivity (logistic or double-logistic) with...

Bayesian Age-Period-Cohort Model of Lung Cancer Mortality

Directory of Open Access Journals (Sweden)

Bhikhari P. Tharu

2015-09-01

Full Text Available Background The objective of this study was to analyze the time trend for lung cancer mortality in the population of the USA by 5 years based on most recent available data namely to 2010. The knowledge of the mortality rates in the temporal trends is necessary to understand cancer burden.Methods Bayesian Age-Period-Cohort model was fitted using Poisson regression with histogram smoothing prior to decompose mortality rates based on age at death, period at death, and birth-cohort.Results Mortality rates from lung cancer increased more rapidly from age 52 years. It ended up to 325 deaths annually for 82 years on average. The mortality of younger cohorts was lower than older cohorts. The risk of lung cancer was lowered from period 1993 to recent periods.Conclusions The fitted Bayesian Age-Period-Cohort model with histogram smoothing prior is capable of explaining mortality rate of lung cancer. The reduction in carcinogens in cigarettes and increase in smoking cessation from around 1960 might led to decreasing trend of lung cancer mortality after calendar period 1993.

Age replacement models: A summary with new perspectives and methods

International Nuclear Information System (INIS)

Zhao, Xufeng; Al-Khalifa, Khalifa N.; Magid Hamouda, Abdel; Nakagawa, Toshio

2017-01-01

Age replacement models are fundamental to maintenance theory. This paper summarizes our new perspectives and hods in age replacement models: First, we optimize the expected cost rate for a required availability level and vice versa. Second, an asymptotic model with simple calculation is proposed by using the cumulative hazard function skillfully. Third, we challenge the established theory such that preventive replacement should be non-random and only corrective replacement should be made for the unit with exponential failure. Fourth, three replacement policies with random working cycles are discussed, which are called overtime replacement, replacement first, and replacement last, respectively. Fifth, the policies of replacement first and last are formulated with general models. Sixth, age replacement is modified for the situation when the economical life cycle of the unit is a random variable with probability distribution. Finally, models of a parallel system with constant and random number of units are taken into considerations. The models of expected cost rates are obtained and optimal replacement times to minimize them are discussed analytically and computed numerically. Further studies and potential applications are also indicated at the end of discussions of the above models. - Highlights: • Optimization of cost rate for availability level is discussed and vice versa. • Asymptotic and random replacement models are discussed. • Overtime replacement, replacement first and replacement last are surveyed. • Replacement policy with random life cycle is given. • A parallel system with random number of units is modeled.

Econometric model for age- and population-dependent radiation exposures

International Nuclear Information System (INIS)

Sandquist, G.M.; Slaughter, D.M.; Rogers, V.C.

1991-01-01

The economic impact associated with ionizing radiation exposures in a given human population depends on numerous factors including the individual's mean economic status as a function age, the age distribution of the population, the future life expectancy at each age, and the latency period for the occurrence of radiation-induced health effects. A simple mathematical model has been developed that provides an analytical methodology for estimating the societal econometrics associated with radiation effects are to be assessed and compared for economic evaluation

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

Science.gov (United States)

Levy, Sheri R

2018-03-19

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.

Robinson's Computerized Strabismus Model Comes of Age

NARCIS (Netherlands)

H.J. Simonsz (Huib); H. Spekreijse (Henk)

1996-01-01

textabstractIn this article we review our further development of D.A. Robinson's computerized strabismus model. First, an extensive literature study has been carried out to get more accurate data on the anatomy of the average eye and the eye muscles, and about how these vary with age and with

Model for the age-dependent skeletal retention of plutonium

International Nuclear Information System (INIS)

Leggett, R.W.; Eckerman, K.F.

1984-01-01

A mathematical model of the metabolic and physiologic processes involved in the retention and translocation of plutonium in the body. The implications of the model concerning the dose as a function of age to radiosensitive tissues of the skeleton are examined. 16 references, 1 figure

An aging elasto-viscoplastic model for ceramics

International Nuclear Information System (INIS)

Soulacroix, Julian; Michel, Bruno; Gatt, Jean-Marie; Kubler, Regis; Barrallier, Laurent

2014-01-01

A model reproducing strain softening behavior in ceramic materials is proposed. This model is base on a critical treatment of previous mechanical experimental results, mainly on uranium dioxide. The main hypothesis is that the strain softening phenomenon is related to an aging process, where some point defects move towards the dislocations and modify their velocity. This is different from most of models used up to now, as they were based on the hypothesis that only the initial lack of dislocations was responsible of the strain softening behavior. A model is first developed in a simple 1D framework. Evolution of the mechanical behavior with strain rate and temperature is well reproduced by this model. Then, the 1D model is extended to a 3D mechanical model, and mechanical compressive tests on UO 2 pellets are simulated. The 3D model well reproduces the observed asymmetrical shape of the compressed pellet if one considers that the material is not initially perfectly homogeneous, which highlights the importance of accounting for spatial heterogeneity of materials in models. (authors)

Early-age behaviour of concrete in massive structures, experimentation and modelling

International Nuclear Information System (INIS)

Zreiki, J.; Bouchelaghem, F.; Chaouche, M.

2010-01-01

This study is focused on the behaviour of concrete at early-age in massive structures, in relation with the prediction of both cracking risk and residual stresses, which is still a challenging task. In this paper, a 3D thermo-chemo-mechanical model has been developed, on the basis of complete material characterization experiments, in order to predict the early-age development of strains and residual stresses, and in order to assess the risk of cracking in massive concrete structures. The parameters of the proposed model were identified on two different concretes, High Performance Concrete and Fibrous Self-Compacted Concrete - from simple experiments in the laboratory: uniaxial tension and compression tests, dynamic Young's modulus measurements, free and autogenous shrinkages, semi-adiabatic calorimetry. The proposed model has been implemented in a Finite Element code, and the numerical simulations of the laboratory tests have proved the model consistency. Furthermore, early-age experiments conducted on massive structures have also been simulated, in order to investigate the predictive capability of the model, and to assess the model performance in practical situations where varying temperatures are involved.

Modeling of an Aged Porous Silicon Humidity Sensor Using ANN Technique

Directory of Open Access Journals (Sweden)

Tarikul ISLAM

2006-10-01

Full Text Available Porous silicon (PS sensor based on capacitive technique used for measuring relative humidity has the advantages of low cost, ease of fabrication with controlled structure and CMOS compatibility. But the response of the sensor is nonlinear function of humidity and suffers from errors due to aging and stability. One adaptive linear (ADALINE ANN model has been developed to model the behavior of the sensor with a view to estimate these errors and compensate them. The response of the sensor is represented by third order polynomial basis function whose coefficients are determined by the ANN technique. The drift in sensor output due to aging of PS layer is also modeled by adapting the weights of the polynomial function. ANN based modeling is found to be more suitable than conventional physical modeling of PS humidity sensor in changing environment and drift due to aging. It helps online estimation of nonlinearity as well as monitoring of the fault of the PS humidity sensor using the coefficients of the model.

Age structure and capital dilution effects in neo-classical growth models.

Science.gov (United States)

Blanchet, D

1988-01-01

Economists often over estimate capital dilution effects when applying neoclassical growth models which use age structured population and depreciation of capital stock. This occurs because capital stock is improperly characterized. A standard model which assumes a constant depreciation of capital intimates that a population growth rate equal to a negative constant savings ratio is preferable to any higher growth rate. Growth rates which are lower than a negative constant savings ratio suggest an ever growing capital/labor ratio and an ever growing standard of living, even if people do not save. This is suggested because the natural reduction of the capital stock through depreciation is slower than the population decrease which is simply unrealistic. This model overlooks the fact that low or negative growth rates result in an ageing of the capital stock, and this ageing subsequently results in an increase of the overall rate of capital depreciation. In that overly simplistic model, depreciation was assumed independent of the age of the captial stock. Incorporating depreciation as a variable into a model allows a more symmetric treatment of capital. Using models with heterogenous capital, this article explores what occurs when more than 1 kind of capital good is involved in production and when these various captial goods have different lengths of life. Applying economic models, it also examines what occurs when the length of life of capital may vary. These variations correct the negative impact that population growth can have on per capital production and consumption.

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

2008-01-01

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 ΔPaPls1 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 ΔPaPls1 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. PMID:18757568

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

International Nuclear Information System (INIS)

Zhang Guiqing; Chen Tianlun

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.

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.

Decision support for life extension of technical systems through virtual age modelling

International Nuclear Information System (INIS)

Pérez Ramírez, Pedro A.; Utne, Ingrid Bouwer

2013-01-01

This article presents a virtual age model for decision support regarding life extension of ageing repairable systems. The aim of the model is to evaluate different life extension decision alternatives and their impact on the future performance of the system. The model can be applied to systems operated continuously (e.g., process systems) and systems operated on demand (e.g., safety systems). Deterioration and efficiency of imperfect maintenance is assessed when there is limited or no degradation data, and only failure and maintenance data is available. Systems that are in operation can be studied, meaning that the systems may be degraded. The current degradation is represented by a “current virtual age”, which is calculated from recorded maintenance data. The model parameters are estimated with the maximum likelihood method. A case study illustrates the application of the model for life extension of two fire water pumps in an oil and gas facility. The performance of the pump system is assessed with respect to number of failures, safety unavailability and costs during the life extension period. -- Highlights: ► Life extension assessment of technical systems using virtual age model is proposed. ► A virtual age model is generalised for systems in stand-by and continuous operation. ► The concept of current virtual age describes technical condition of the system. ► Different decision alternatives for life extension can be easily analysed. ► The decision process is improved even when only scarce failure data is available

Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival

Directory of Open Access Journals (Sweden)

Céline Christiansen-Jucht

2015-05-01

Full Text Available Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a “standard” model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors.

A whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation

Directory of Open Access Journals (Sweden)

Mc Auley Mark T

2012-10-01

Full Text Available Abstract Background Global demographic changes have stimulated marked interest in the process of aging. There has been, and will continue to be, an unrelenting rise in the number of the oldest old ( >85 years of age. Together with an ageing population there comes an increase in the prevalence of age related disease. Of the diseases of ageing, cardiovascular disease (CVD has by far the highest prevalence. It is regarded that a finely tuned lipid profile may help to prevent CVD as there is a long established relationship between alterations to lipid metabolism and CVD risk. In fact elevated plasma cholesterol, particularly Low Density Lipoprotein Cholesterol (LDL-C has consistently stood out as a risk factor for having a cardiovascular event. Moreover it is widely acknowledged that LDL-C may rise with age in both sexes in a wide variety of groups. The aim of this work was to use a whole-body mathematical model to investigate why LDL-C rises with age, and to test the hypothesis that mechanistic changes to cholesterol absorption and LDL-C removal from the plasma are responsible for the rise. The whole-body mechanistic nature of the model differs from previous models of cholesterol metabolism which have either focused on intracellular cholesterol homeostasis or have concentrated on an isolated area of lipoprotein dynamics. The model integrates both current and previously published data relating to molecular biology, physiology, ageing and nutrition in an integrated fashion. Results The model was used to test the hypothesis that alterations to the rate of cholesterol absorption and changes to the rate of removal of LDL-C from the plasma are integral to understanding why LDL-C rises with age. The model demonstrates that increasing the rate of intestinal cholesterol absorption from 50% to 80% by age 65 years can result in an increase of LDL-C by as much as 34 mg/dL in a hypothetical male subject. The model also shows that decreasing the rate of hepatic

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.

Extending PSA models including ageing and asset management - 15291

International Nuclear Information System (INIS)

Martorell, S.; Marton, I.; Carlos, S.; Sanchez, A.I.

2015-01-01

This paper proposes a new approach to Ageing Probabilistic Safety Assessment (APSA) modelling, which is intended to be used to support risk-informed decisions on the effectiveness of maintenance management programs and technical specification requirements of critical equipment of Nuclear Power Plants (NPP) within the framework of the Risk Informed Decision Making according to R.G. 1.174 principles. This approach focuses on the incorporation of not only equipment ageing but also effectiveness of maintenance and efficiency of surveillance testing explicitly into APSA models and data. This methodology is applied to a motor-operated valve of the auxiliary feed water system (AFWS) of a PWR. This simple example of application focuses on a critical safety-related equipment of a NPP in order to evaluate the risk impact of considering different approaches to APSA and the combined effect of equipment ageing and maintenance and testing alternatives along NPP design life. The risk impact of several alternatives in maintenance strategy is discussed

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

Directory of Open Access Journals (Sweden)

Jones Janette JL

2009-03-01

Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

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. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Early-age behaviour of concrete in massive structures, experimentation and modelling

Energy Technology Data Exchange (ETDEWEB)

Zreiki, J., E-mail: zreiki@lmt.ens-cachan.f [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France); Bouchelaghem, F. [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France); UPMC Univ Paris 06 (France); Chaouche, M. [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France)

2010-10-15

This study is focused on the behaviour of concrete at early-age in massive structures, in relation with the prediction of both cracking risk and residual stresses, which is still a challenging task. In this paper, a 3D thermo-chemo-mechanical model has been developed, on the basis of complete material characterization experiments, in order to predict the early-age development of strains and residual stresses, and in order to assess the risk of cracking in massive concrete structures. The parameters of the proposed model were identified on two different concretes, High Performance Concrete and Fibrous Self-Compacted Concrete - from simple experiments in the laboratory: uniaxial tension and compression tests, dynamic Young's modulus measurements, free and autogenous shrinkages, semi-adiabatic calorimetry. The proposed model has been implemented in a Finite Element code, and the numerical simulations of the laboratory tests have proved the model consistency. Furthermore, early-age experiments conducted on massive structures have also been simulated, in order to investigate the predictive capability of the model, and to assess the model performance in practical situations where varying temperatures are involved.

A New Form of Nondestructive Strength-Estimating Statistical Models Accounting for Uncertainty of Model and Aging Effect of Concrete

International Nuclear Information System (INIS)

Hong, Kee Jeung; Kim, Jee Sang

2009-01-01

As concrete ages, the surrounding environment is expected to have growing influences on the concrete. As all the impacts of the environment cannot be considered in the strength-estimating model of a nondestructive concrete test, the increase in concrete age leads to growing uncertainty in the strength-estimating model. Therefore, the variation of the model error increases. It is necessary to include those impacts in the probability model of concrete strength attained from the nondestructive tests so as to build a more accurate reliability model for structural performance evaluation. This paper reviews and categorizes the existing strength-estimating statistical models of nondestructive concrete test, and suggests a new form of the strength-estimating statistical models to properly reflect the model uncertainty due to aging of the concrete. This new form of the statistical models will lay foundation for more accurate structural performance evaluation.

A model for ageing-home-care service process improvement

OpenAIRE

Yu, Shu-Yan; Shie, An-Jin

2017-01-01

The purpose of this study was to develop an integrated model to improve service processes in ageing-home-care. According to the literature, existing service processes have potential service failures that affect service quality and efficacy. However, most previous studies have only focused on conceptual model development using New Service Development (NSD) and fail to provide a systematic model to analyse potential service failures and facilitate managers developing solutions to improve the se...

[The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

Science.gov (United States)

Bashkireva, A S

2012-01-01

The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

The basic approach to age-structured population dynamics models, methods and numerics

CERN Document Server

Iannelli, Mimmo

2017-01-01

This book provides an introduction to age-structured population modeling which emphasises the connection between mathematical theory and underlying biological assumptions. Through the rigorous development of the linear theory and the nonlinear theory alongside numerics, the authors explore classical equations that describe the dynamics of certain ecological systems. Modeling aspects are discussed to show how relevant problems in the fields of demography, ecology, and epidemiology can be formulated and treated within the theory. In particular, the book presents extensions of age-structured modelling to the spread of diseases and epidemics while also addressing the issue of regularity of solutions, the asymptotic behaviour of solutions, and numerical approximation. With sections on transmission models, non-autonomous models and global dynamics, this book fills a gap in the literature on theoretical population dynamics. The Basic Approach to Age-Structured Population Dynamics will appeal to graduate students an...

Building from a conceptual model of the resilience process during ageing, towards the Groningen Aging Resilience Inventory.

Science.gov (United States)

van Abbema, Renske; Bielderman, Annemiek; De Greef, Mathieu; Hobbelen, Hans; Krijnen, Wim; van der Schans, Cees

2015-09-01

To develop and psychometrically test the Groningen Ageing Resilience Inventory. Ageing is a process that is often accompanied by functional limitation, disabilities and losses. Instead of focusing on these negative events of ageing, there are opportunities in focusing on adaptation mechanisms, like resilience, that are helpful to cope with those adversities. Cross-sectional study. The study was conducted from 2011-2012. First, a conceptual model of resilience during the ageing process was constructed. Next, items were formulated that made up a comprehensive template questionnaire reflecting the model. Finally, a cross-sectional study was performed to evaluate the construct validity and internal consistency of this template 16-item questionnaire. Participants (N = 229) with a mean age of 71·5 years, completed the template 16-item Groningen Ageing Resilience Inventory, and performance based tests and psychological questionnaires. Exploratory factor analysis resulted in a two factor solution of internal and external resources of resilience. Three items did not discriminate well between the two factors and were deleted, remaining a final 13-item questionnaire that shows evidence of good internal consistency. The direction and magnitude of the correlations with other measures support the construct validity. The Groningen Ageing Resilience Inventory is a useful instrument that can help nurses, other healthcare workers, researchers and providers of informal care to identify the internal and external resources of resilience in individuals and groups. In a multidisciplinary biopsychosocial approach this knowledge provides tools for empowering older patients in performing health promoting behaviors and self-care tasks. © 2015 John Wiley & Sons Ltd.

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.

Genetic mouse models of brain ageing and Alzheimer's disease.

Science.gov (United States)

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

Science.gov (United States)

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

Science.gov (United States)

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

Two-dimensional chronostratigraphic modelling of OSL ages from recent beach-ridge deposits, SE Australia

DEFF Research Database (Denmark)

Tamura, Toru; Cunningham, Alastair C.; Oliver, Thomas S.N.

2018-01-01

Optically-stimulated luminesecne (OSL) dating, in concert with two-dimensional ground-penetrating radar (GPR) profiling, has contributed to significant advances in our understanding of beach-ridge systems and other sedimentary landforms in various settings. For recent beach-ridges, the good OSL...... samples may be larger than the difference in sample ages. Age inversions can be avoided, however, if the stratigraphic constraints are included in the age estimation process. Here, we create a custom Bayesian chronological model for a recent (..., for direct comparison with a GPR profile. The model includes a full ‘burial-dose model’ for each sample and a dose rate term with the modelled ages constrained by the vertical and shore-normal sample order. The modelled ages are visualized by plotting isochrones on the beach-ridge cross section...

Age-dependent reliability model considering effects of maintenance and working conditions

International Nuclear Information System (INIS)

Martorell, Sebastian; Sanchez, Ana; Serradell, Vicente

1999-01-01

Nowadays, there is some doubt about building new nuclear power plants (NPPs). Instead, there is a growing interest in analyzing the possibility to extend current NPP operation, where life management programs play an important role. The evolution of the NPP safety depends on the evolution of the reliability of its safety components, which, in turn, is a function of their age along the NPP operational life. In this paper, a new age-dependent reliability model is presented, which includes parameters related to surveillance and maintenance effectiveness and working conditions of the equipment, both environmental and operational. This model may be used to support NPP life management and life extension programs, by improving or optimizing surveillance and maintenance tasks using risk and cost models based on such an age-dependent reliability model. The results of the sensitivity study in the example application show that the selection of the most appropriate maintenance strategy would directly depend on the previous parameters. Then, very important differences are expected to appear under certain circumstances, particularly, in comparison with other models that do not consider maintenance effectiveness and working conditions simultaneously

Multi-physics Model for the Aging Prediction of a Vanadium Redox Flow Battery System

International Nuclear Information System (INIS)

Merei, Ghada; Adler, Sophie; Magnor, Dirk; Sauer, Dirk Uwe

2015-01-01

Highlights: • Present a multi-physics model of vanadium redox-flow battery. • This model is essential for aging prediction. • It is applicable for VRB system of different power and capacity ratings. • Good results comparing with current research in this field. - Abstract: The all-vanadium redox-flow battery is an attractive candidate to compensate the fluctuations of non-dispatchable renewable energy generation. While several models for vanadium redox batteries have been described yet, no model has been published, which is adequate for the aging prediction. Therefore, the present paper presents a multi-physics model which determines all parameters that are essential for an aging prediction. In a following paper, the corresponding aging model of vanadium redox flow battery (VRB) is described. The model combines existing models for the mechanical losses and temperature development with new approaches for the batteries side reactions. The model was implemented in Matlab/Simulink. The modeling results presented in the paper prove to be consistent with the experimental results of other research groups

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.

Basis for the ICRP's age-specific biokinetic model for uranium

International Nuclear Information System (INIS)

Leggett, R.W.

1994-01-01

In an effort motivated largely by the Chernobyl nuclear accident, the International Commission on Radiological Protection (ICRP) is developing age-specific biokinetic models and dose coefficients for environmentally important radionuclides. This paper describes the ICRP's age-specific biokinetic model for uranium. The model is constructed within a physiologically based framework originally developed for application to the alkaline earth elements but sufficiently general to apply to the larger class of bone-volume-seeking elements. Transfer rates for a reference adult are based mainly on: (1) measurements of uranium in blood and excreta of several human subjects who were intravenously injected with uranium; (2) postmortem measurements of uranium in tissues of some of those subjects; (3) postmortem measurements of uranium in tissues of occupationally and non-occupationally exposed subjects; (4) data on baboons, dogs, and smaller laboratory animals exposed to uranium for experimental purposes; and (5) consideration of the physiological processes thought to control retention and translocation of uranium in the body. Transfer rates for the adult are extended to children by application of a set of generic assumptions applied by the ICRP to calcium-like elements. These assumptions were derived mainly from observations of the age-specific biokinetics of the alkaline earth elements and lead in humans and laboratory animals but are consistent with available age-specific biokinetic data on uranium. 82 refs., 17 figs., 8 tabs

A Mathematical Model Of Ageing In Man Due To Gene Loss | Mbah ...

African Journals Online (AJOL)

Aging is as a result of dysfunction of the body mechanisms due to failure of one organelle, tissue, component or the other. In man there is a pointer towards gene loss as a primary cause of ageing. In this paper we develop a mathematical model describing changes in gene efficiency or gene failure. This model is used to ...

Modeling Fetal Weight for Gestational Age: A Comparison of a Flexible Multi-level Spline-based Model with Other Approaches

Science.gov (United States)

Villandré, Luc; Hutcheon, Jennifer A; Perez Trejo, Maria Esther; Abenhaim, Haim; Jacobsen, Geir; Platt, Robert W

2011-01-01

We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest. PMID:21931571

Epidemic model with vaccinated age that exhibits backward bifurcation

International Nuclear Information System (INIS)

Yang Junyuan; Zhang Fengqin; Li Xuezhi

2009-01-01

Vaccination of susceptibilities is included in a transmission model for a disease that confers immunity. In this paper, interplay of vaccination strategy together with vaccine efficacy and the vaccinated age is studied. In particular, vaccine efficacy can lead to a backward bifurcation. At the same time, we also discuss an abstract formulation of the problem, and establish the well-posedness of the model.

Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens.

Science.gov (United States)

Urs, Raksha; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

2010-06-01

To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Profiles of whole isolated human lenses (n=30) aged 20-69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-co-ordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 microm. The age-dependent equations provide a reliable lens model for ages 20-60 years. The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Significance of categorization and the modeling of age related factors for radiation protection

International Nuclear Information System (INIS)

Matsuoka, Osamu

1987-01-01

It is proposed that the categorization and modelling are necessary with regard to age related factors of radionuclide metabolism for the radiation protection of the public. In order to utilize the age related information as a model for life time risk estimate of public, it is necessary to generalize and simplify it according to the categorized model patterns. Since the patterns of age related changes in various parameters of radionuclide metabolism seem to be rather simple, it is possible to categorize them into eleven types of model patterns. Among these models, five are selected as positively significant models to be considered. Examples are shown as to the fitting of representative parameters of both physiological and metabolic parameter of radionuclides into the proposed model. The range of deviation from adult standard value is also analyzed for each model. The fitting of each parameter to categorized models, and its comparative consideration provide the effective information as to the physiological basis of radionuclide metabolism. Discussions are made on the problems encountered in the application of available age related information to radiation protection of the public, i.e. distribution of categorized parameter, period of life covered, range of deviation from adult value, implication to other dosimetric and pathological models and to the final estimation. 5 refs.; 3 figs.; 4 tabs

Adaptive model of the aging emmetropic eye and its changes with accommodation.

Science.gov (United States)

Navarro, Rafael

2014-11-20

A general schematic model of the optical system of the emmetropic human eye is proposed, capable of adapting to changes with age and accommodation through adjustment of the optical surfaces and the internal gradient index structure of the lens. The specific models of the cornea and lens consist of minor generalizations of previous work by assuming them to be the sum of a biconic plus three higher order Zernike modes. The internal gradient index distribution adapts to the external shape so that the analytical expression is invariant with the changes with age and accommodation. The model also includes tips, tilts, and decentrations of the surfaces according to experimental findings. The specific parameters of these models are either constants or functions of age and/or accommodation. The model is polychromatic, and its optical performance was evaluated along the keratometric axis. Chromatic aberrations (longitudinal and transverse), astigmatism, coma, trefoil, and spherical aberration show good agreement with experimental averages. The change of these aberrations as a function of age or accommodation is also consistent with experimental findings (except for trefoil in eyes older than 50 years). This means that the average structure seems to predict the average performance. Nevertheless, the present model is too schematic to account for other higher order aberrations, such as tetrafoil, also present in real eyes. © 2014 ARVO.

Advanced age negatively impacts survival in an experimental brain tumor model.

Science.gov (United States)

Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

2016-09-06

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The importance of age-related decline in forest NPP for modeling regional carbon balances.

Science.gov (United States)

Zaehle, Sönke; Sitch, Stephen; Prentice, I Colin; Liski, Jari; Cramer, Wolfgang; Erhard, Markus; Hickler, Thomas; Smith, Benjamin

2006-08-01

We show the implications of the commonly observed age-related decline in aboveground productivity of forests, and hence forest age structure, on the carbon dynamics of European forests in response to historical changes in environmental conditions. Size-dependent carbon allocation in trees to counteract increasing hydraulic resistance with tree height has been hypothesized to be responsible for this decline. Incorporated into a global terrestrial biosphere model (the Lund-Potsdam-Jena model, LPJ), this hypothesis improves the simulated increase in biomass with stand age. Application of the advanced model, including a generic representation of forest management in even-aged stands, for 77 European provinces shows that model-based estimates of biomass development with age compare favorably with inventory-based estimates for different tree species. Model estimates of biomass densities on province and country levels, and trends in growth increment along an annual mean temperature gradient are in broad agreement with inventory data. However, the level of agreement between modeled and inventory-based estimates varies markedly between countries and provinces. The model is able to reproduce the present-day age structure of forests and the ratio of biomass removals to increment on a European scale based on observed changes in climate, atmospheric CO2 concentration, forest area, and wood demand between 1948 and 2000. Vegetation in European forests is modeled to sequester carbon at a rate of 100 Tg C/yr, which corresponds well to forest inventory-based estimates.

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.

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.

Mathematical modelling the age dependence of Epstein-Barr virus associated infectious mononucleosis.

Science.gov (United States)

Huynh, Giao T; Adler, Frederick R

2012-09-01

Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Primary EBV infection in adolescents and young adults, however, often leads to infectious mononucleosis (IM) with symptoms including fever, fatigue and sore throat that can persist for months. Expansion in the number of CD8(+) T cells, especially against EBV lytic proteins, are the main cause of these symptoms. We propose a mathematical model for the regulation of EBV infection within a host to address the dependence of IM on age. This model tracks the number of virus, infected B cell and epithelial cell and CD8(+) T-cell responses to the infection. We use this model to investigate three hypotheses for the high incidence of IM in teenagers and young adults: saliva and antibody effects that increase with age, high cross-reactive T-cell responses and a high initial viral load. The model supports the first two of these hypotheses and suggests that variation in host antibody responses and the complexity of the pre-existing cross-reactive T-cell repertoire, both of which depend on age, may play important roles in the etiology of IM.

Modeling and Analysis of a Nonlinear Age-Structured Model for Tumor Cell Populations with Quiescence

Science.gov (United States)

Liu, Zijian; Chen, Jing; Pang, Jianhua; Bi, Ping; Ruan, Shigui

2018-05-01

We present a nonlinear first-order hyperbolic partial differential equation model to describe age-structured tumor cell populations with proliferating and quiescent phases at the avascular stage in vitro. The division rate of the proliferating cells is assumed to be nonlinear due to the limitation of the nutrient and space. The model includes a proportion of newborn cells that enter directly the quiescent phase with age zero. This proportion can reflect the effect of treatment by drugs such as erlotinib. The existence and uniqueness of solutions are established. The local and global stabilities of the trivial steady state are investigated. The existence and local stability of the positive steady state are also analyzed. Numerical simulations are performed to verify the results and to examine the impacts of parameters on the nonlinear dynamics of the model.

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

The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.

Science.gov (United States)

Vanhooren, Valerie; Libert, Claude

2013-01-01

The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging. Copyright © 2012 Elsevier B.V. All rights reserved.

ON THE RELIABILITY OF STELLAR AGES AND AGE SPREADS INFERRED FROM PRE-MAIN-SEQUENCE EVOLUTIONARY MODELS

International Nuclear Information System (INIS)

Hosokawa, Takashi; Offner, Stella S. R.; Krumholz, Mark R.

2011-01-01

We revisit the problem of low-mass pre-main-sequence stellar evolution and its observational consequences for where stars fall on the Hertzsprung-Russell diagram (HRD). In contrast to most previous work, our models follow stars as they grow from small masses via accretion, and we perform a systematic study of how the stars' HRD evolution is influenced by their initial radius, by the radiative properties of the accretion flow, and by the accretion history, using both simple idealized accretion histories and histories taken from numerical simulations of star cluster formation. We compare our numerical results to both non-accreting isochrones and to the positions of observed stars in the HRD, with a goal of determining whether both the absolute ages and the age dispersions inferred from non-accreting isochrones are reliable. We show that non-accreting isochrones can sometimes overestimate stellar ages for more massive stars (those with effective temperatures above ∼3500 K), thereby explaining why non-accreting isochrones often suggest a systematic age difference between more and less massive stars in the same cluster. However, we also find the only way to produce a similar overestimate for the ages of cooler stars is if these stars grow from ∼0.01 M sun seed protostars that are an order of magnitude smaller than predicted by current theoretical models, and if the size of the seed protostar correlates systematically with the final stellar mass at the end of accretion. We therefore conclude that, unless both of these conditions are met, inferred ages and age spreads for cool stars are reliable, at least to the extent that the observed bolometric luminosities and temperatures are accurate. Finally, we note that the time dependence of the mass accretion rate has remarkably little effect on low-mass stars' evolution on the HRD, and that such time dependence may be neglected for all stars except those with effective temperatures above ∼4000 K.

Societal Aging in the Netherlands : Exploratory System Dynamics Modeling and Analysis

NARCIS (Netherlands)

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

2012-01-01

Mismanagement of societal aging is an important threat to health care systems, social security systems, 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 as a scenario

Study on Developing Degradation Model for Nuclear Power Plants With Ageing Elements Affected on Operation Parameter

International Nuclear Information System (INIS)

Choi, Yong Won; Lim, Sung Won; Lee, Un Chul; Kim, Man Woong; Kim, Kab; Ryu, Yong Ho

2009-01-01

As a part of development the evaluation system of safety margin effects for degradation of CANDU reactors, it is required that the degradation model represents the distribution of each ageing factor's value during operating year. Unfortunately, it is not easy to make an explicit relation between the RELAP-CANDU parameters and ageing mechanism because of insufficient data and lack of applicable models. So, operating parameter related with ageing is used for range determination of ageing factor. Then, relation between operating parameter and ageing elements is analyzed and ageing constant values for degradation model are determined. Also the other ageing factor is derived for more accurate ageing analysis

The "Village" model: a consumer-driven approach for aging in place.

Science.gov (United States)

Scharlach, Andrew; Graham, Carrie; Lehning, Amanda

2012-06-01

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. Thirty of 42 fully operational Villages completed 2 surveys. One survey examined Villages' member characteristics, membership types, and fee structures. An additional survey collected information about organizational mission, goals, methods of operation, funding sources, challenges, and older adults' roles. Villages provide a variety of support services designed to help members age in place, meet service needs, and promote health and quality of life. Most Villages operate relatively autonomously, relying primarily on member fees and donations. Village members typically are highly involved in organizational development and oversight and provide services to other members in almost half of the Villages. Members predominantly are aged 65 years or older, White, non-Hispanic, homeowners, and have care needs that are slightly lower than those of the elderly U.S. population overall. Villages are a promising model for addressing service needs among middle-class seniors who seek to age in their own homes and communities. Financial sustainability is apt to be a challenge unless Villages secure more stable sources of funding. Organizational sustainability may be promoted through affiliations with social service agencies and other sources of technical and financial assistance. Future evaluation is needed regarding the impact of Villages on elders' ability to age in place as well as the long-term sustainability of the Village model.

Determination of timescales of nitrate contamination by groundwater age models in a complex aquifer system

Science.gov (United States)

Koh, E. H.; Lee, E.; Kaown, D.; Lee, K. K.; Green, C. T.

2017-12-01

Timing and magnitudes of nitrate contamination are determined by various factors like contaminant loading, recharge characteristics and geologic system. Information of an elapsed time since recharged water traveling to a certain outlet location, which is defined as groundwater age, can provide indirect interpretation related to the hydrologic characteristics of the aquifer system. There are three major methods (apparent ages, lumped parameter model, and numerical model) to date groundwater ages, which differently characterize groundwater mixing resulted by various groundwater flow pathways in a heterogeneous aquifer system. Therefore, in this study, we compared the three age models in a complex aquifer system by using observed age tracer data and reconstructed history of nitrate contamination by long-term source loading. The 3H-3He and CFC-12 apparent ages, which did not consider the groundwater mixing, estimated the most delayed response time and a highest period of the nitrate loading had not reached yet. However, the lumped parameter model could generate more recent loading response than the apparent ages and the peak loading period influenced the water quality. The numerical model could delineate various groundwater mixing components and its different impacts on nitrate dynamics in the complex aquifer system. The different age estimation methods lead to variations in the estimated contaminant loading history, in which the discrepancy in the age estimation was dominantly observed in the complex aquifer system.

Modelling regional variation of first-time births in Denmark 1980-1994 by an age-period-cohort model

Directory of Open Access Journals (Sweden)

Lisbeth B. Knudsen

2005-12-01

Full Text Available Despite the small size of Denmark, there have traditionally been rather consistent regional differences in fertility rates. We apply the statistical age-period-cohort model to include the effect of these three time-related factors thereby concisely illuminating the regional differences of first-time births in Denmark. From the Fertility of Women and Couples Dataset we obtain data on number of births by nulliparous women by year (1980-1994, age (15-45 and county of residence. We show that the APC-model describes the fertility rates of nulliparous women satisfactorily. To catch the regional variation an interaction parameter between age and county is necessary, which provides a surprisingly good description suggesting that the county-specific age-distributions of first-time fertility rates differ. Our results are in general agreement with the 'moral geography' concepts of Tonboe (2001.

Modelling regional variation of first-time births in Denmark 1980-1994 by an age-period-cohort model

DEFF Research Database (Denmark)

Thygesen, Lau Caspar; Knudsen, Lisbeth B.; Keiding, Niels

2005-01-01

Despite the small size of Denmark, there have traditionally been rather consistent regional differences in fertility rates. We apply the statistical age-period-cohort model to include the effect of these three time-related factors thereby concisely illuminating the regional differences of first......-time births in Denmark. From the Fertility of Women and Couples Dataset we obtain data on number of births by nulliparous women by year (1980-1994), age (15-45) and county of residence. We show that the APC-model describes the fertility rates of nulliparous women satisfactorily. To catch the regional...... variation an interaction parameter between age and county is necessary, which provides a surprisingly good description suggesting that the county-specific age-distributions of first-time fertility rates differ. Our results are in general agreement with the 'moral geography' concepts of Tonboe (2001)....

Precise age for the Permian-Triassic boundary in South China from high-precision U-Pb geochronology and Bayesian age-depth modeling

Science.gov (United States)

Baresel, Björn; Bucher, Hugo; Brosse, Morgane; Cordey, Fabrice; Guodun, Kuang; Schaltegger, Urs

2017-03-01

This study is based on zircon U-Pb ages of 12 volcanic ash layers and volcanogenic sandstones from two deep water sections with conformable and continuous formational Permian-Triassic boundaries (PTBs) in the Nanpanjiang Basin (South China). Our dates of single, thermally annealed and chemically abraded zircons bracket the PTB in Dongpan and Penglaitan and provide the basis for a first proof-of-concept study utilizing a Bayesian chronology model comparing the three sections of Dongpan, Penglaitan and the Global Stratotype Section and Point (GSSP) at Meishan. Our Bayesian modeling demonstrates that the formational boundaries in Dongpan (251.939 ± 0.030 Ma), Penglaitan (251.984 ± 0.031 Ma) and Meishan (251.956 ± 0.035 Ma) are synchronous within analytical uncertainty of ˜ 40 ka. It also provides quantitative evidence that the ages of the paleontologically defined boundaries, based on conodont unitary association zones in Meishan and on macrofaunas in Dongpan, are identical and coincide with the age of the formational boundaries. The age model also confirms the extreme condensation around the PTB in Meishan, which distorts the projection of any stratigraphic points or intervals onto other more expanded sections by means of Bayesian age-depth models. Dongpan and Penglaitan possess significantly higher sediment accumulation rates and thus offer a greater potential for high-resolution studies of environmental proxies and correlations around the PTB than Meishan. This study highlights the power of high-resolution radio-isotopic ages that allow a robust intercalibration of patterns of biotic changes and fluctuating environmental proxies and will help recognizing their global, regional or local significance.

Ageing effects modelling in probabilistic safety assessment of nuclear power plants

International Nuclear Information System (INIS)

Nitoi, M.; Turcu, I.; Florescu, G.; Apostol, M.; Farcasiu, M.; Pavelescu, M.

2005-01-01

Ageing management has become a major concern for many responsible organizations during the last years, because as the operating power plants have got older, they may have the tendency to become less safe. The effects of age-related degradation of plant components, systems and structures are necessary to be assessed in order to assure a continuous safe operation of nuclear power plants. The Probabilistic Safety Analysis (PSA) is an efficient system analysis method which is used to assess the risk of operation of nuclear power plants. In the assessment of risk level for a plant, most of the PSA studies generally didn't take into account the ageing effects, and uses a time averaged unavailability. By incorporation of ageing effects, the results enable an identification of the components that have the greatest effect on risk if their failure rates increase due to ageing effects modelling. In this paper, it was assessed the impact on Class IV Electrical Power System unavailability of the assumed increase in components failure probability caused by components ageing. The electrical system was chosen for the study because there are a lot of cables and for these types of equipment there is no planned preventive or corrective maintenance, and they are originally designed to reach the end of plant life with an adequate safety margin. To quantify the effects of age-related degradation on components, the linear ageing model was used. In this model, the failure rate of a component λ (t) is expressed as a sum of two independent failure rates, one associated with random failure, λ 0 , and the other associated with failures due to aging α, so: λ(t) = λ 0 + αt. The basic events were coded using a computer code similar to CAFTA, developed in INR Pitesti. For the reliability data allocation for basic events a intern data base was used. This data base contains data from the following generic data bases: IAEA Component Reliability Data for use in PSA, Point Lepreau Component

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. © 2013 Wiley Publishing Asia Pty Ltd.

Models for predicting turnover of residential aged care nurses: a structural equation modelling analysis of secondary data.

Science.gov (United States)

Gao, Fengsong; Newcombe, Peter; Tilse, Cheryl; Wilson, Jill; Tuckett, Anthony

2014-09-01

Nurse turnover in the residential aged care industry is a pressing issue. Researchers have shown ongoing interest in exploring how the factors that are amendable to change in aged care policy, regulation and funding and in organizational procedures (e.g. job demands, coping resources and psychological health of nurses) impact on turnover. However, the findings are mixed. This study tested two theoretical models of turnover to examine the structural relationships among job demands, coping resources, psychological health and turnover of residential aged care nurses. Although many previous studies operationalized turnover as intention to leave, the present study investigated actual turnover by following up with the same individuals over time, and thus provided more accurate predictive models of turnover behaviour. The sample, 239 Australian residential aged care nurses, came from the Nurses and Midwives e-cohort Study. Job demands, coping resources, and psychological health were measured using standardized instruments. Structural equation modelling was used to test the measurement and structural models. Controlling for a number of workforce and individual characteristics, coping resources (measured by job control, supervisor support, and co-worker support) were negatively and directly associated with turnover. Additionally, the findings supported the Job Demand-Control-Support model in that higher coping resources and lower job demands (indicated by psychological demands, physical demands, and effort) were related to better psychological health (measured by vitality, social functioning, role emotional, and mental health), and higher job demands were related to lower coping resources. Findings suggest that aged care policy makers and service providers might consider increasing coping resources available to nurses and minimizing job demands of care work to reduce turnover and improve nurses' psychological health. Moreover, findings from this Australian study may provide

Accommodation and age-dependent eye model based on in vivo measurements.

Science.gov (United States)

Zapata-Díaz, Juan F; Radhakrishnan, Hema; Charman, W Neil; López-Gil, Norberto

2018-03-21

To develop a flexible model of the average eye that incorporates changes with age and accommodation in all optical parameters, including entrance pupil diameter, under photopic, natural, environmental conditions. We collated retrospective in vivo measurements of all optical parameters, including entrance pupil diameter. Ray-tracing was used to calculate the wavefront aberrations of the eye model as a function of age, stimulus vergence and pupil diameter. These aberrations were used to calculate objective refraction using paraxial curvature matching. This was also done for several stimulus positions to calculate the accommodation response/stimulus curve. The model predicts a hyperopic change in distance refraction as the eye ages (+0.22D every 10 years) between 20 and 65 years. The slope of the accommodation response/stimulus curve was 0.72 for a 25 years-old subject, with little change between 20 and 45 years. A trend to a more negative value of primary spherical aberration as the eye accommodates is predicted for all ages (20-50 years). When accommodation is relaxed, a slight increase in primary spherical aberration (0.008μm every 10 years) between 20 and 65 years is predicted, for an age-dependent entrance pupil diameter ranging between 3.58mm (20 years) and 3.05mm (65 years). Results match reasonably well with studies performed in real eyes, except that spherical aberration is systematically slightly negative as compared with the practical data. The proposed eye model is able to predict changes in objective refraction and accommodation response. It has the potential to be a useful design and testing tool for devices (e.g. intraocular lenses or contact lenses) designed to correct the eye's optical errors. Copyright © 2018 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Modelling safety of multistate systems with ageing components

Energy Technology Data Exchange (ETDEWEB)

Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna [Gdynia Maritime University, Department of Mathematics ul. Morska 81-87, Gdynia 81-225 Poland (Poland)

2016-06-08

An innovative approach to safety analysis of multistate ageing systems is presented. Basic notions of the ageing multistate systems safety analysis are introduced. The system components and the system multistate safety functions are defined. The mean values and variances of the multistate systems lifetimes in the safety state subsets and the mean values of their lifetimes in the particular safety states are defined. The multi-state system risk function and the moment of exceeding by the system the critical safety state are introduced. Applications of the proposed multistate system safety models to the evaluation and prediction of the safty characteristics of the consecutive “m out of n: F” is presented as well.

Modelling safety of multistate systems with ageing components

International Nuclear Information System (INIS)

Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna

2016-01-01

An innovative approach to safety analysis of multistate ageing systems is presented. Basic notions of the ageing multistate systems safety analysis are introduced. The system components and the system multistate safety functions are defined. The mean values and variances of the multistate systems lifetimes in the safety state subsets and the mean values of their lifetimes in the particular safety states are defined. The multi-state system risk function and the moment of exceeding by the system the critical safety state are introduced. Applications of the proposed multistate system safety models to the evaluation and prediction of the safty characteristics of the consecutive “m out of n: F” is presented as well.

[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.

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

NARCIS (Netherlands)

B. Schumacher (Björn); V. Bartels (Valerie); P. Frommolt (Peter); B. Habermann (Bianca); F. Braun (Fabian); J.L. Schultze (Joachim); M. Roodbergen (Marianne); J.H.J. Hoeijmakers (Jan); P. Nürnberg (Peter); M.E.T. Dollé (Martijn); T. Benzing (Thomas); R.-U. Müller (Roman-Ulrich); C.E. Kurschat (Christine)

2013-01-01

textabstractBackground: Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome

Development of an Age- and Gender-specific Model for Strontium Metabolism in Humans

International Nuclear Information System (INIS)

Shagina, N. B.; Degteva, M. O.; Tolstykh, E. I.

2004-01-01

This paper presents a development of a new biokinetic model for strontium, which accounts for age and gender differences of metabolism in humans. This model was developed based on the long-term follow-up of the residents living on the banks of the Techa River (Southern Urals, Russia) contaminated with 89,90Sr in 1950-1956. The new model uses the structure of ICRP model for strontium but model parameters have been estimated to account for age, gender and population differences in strontium retention and elimination. Estimates of age- and gender-specific model parameters were derived from (a) the results of long-term measurements of 90Sr-body burden for the Techa River population; (b) experimental studies of calcium and strontium metabolism in humans and (c) non-radiological data regarding bone metabolism (mineral content of the body, bone turnover, etc). As a result, the new model satisfactorily describes data on long-term retention of 90Sr in residents of the Techa River settlements of all ages and both genders and also data from studies during the period of global fallout in the UK and the USA and experimental data on strontium retention in humans. The new model can be used to calculate dose from 89,90Sr for the Techa River residents and also for other populations with similar parameters of skeletal maturation and also for other populations with similar parameters of skeletal maturation and involution. (Author) 27 refs

Local Stability Analysis of an Infection-Age Mathematical Model for ...

African Journals Online (AJOL)

Timothy

1Department of Mathematics/Statistics/Computer Science, Federal University of Agriculture, Makurdi, ... ABSTRACT: An infection age structured mathematical model for tuberculosis disease ...... its applications to optimal vaccination strategies.

Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

International Nuclear Information System (INIS)

Killough, G.G.; Eckerman, K.F.

1985-01-01

This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. The model was made to conform to these data requirements by the use of age-specific estimates of the biological half-time of iodine in the thyroid and an age- and sex-dependent representation of the mass of the thyroid. Also, it was assumed that the thyroid burden was maximum 24 hours after administration (the 131 I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K[exp(-μ 1 t) - exp(-μ 2 t)] (μCi), where μ 1 = lambda/sub r/ + lambda/sub i//sup b/ (i = 1, 2), lambda/sub r/ is the radiological decay-rate coefficient, and lambda/sub i//sup b/ are biological removal rate coefficients. The values of lambda/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time of maximum uptake and the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptake at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. The model could prove useful in the dosimetry of very short-lived radioiodines. Tables of age- and sex-dependent coefficients are provided to enable readers to make their own calculations. 12 refs., 5 figs., 4 tabs

Description of cervical cancer mortality in Belgium using Bayesian age-period-cohort models

Science.gov (United States)

2009-01-01

Objective To correct cervical cancer mortality rates for death cause certification problems in Belgium and to describe the corrected trends (1954-1997) using Bayesian models. Method Cervical cancer (cervix uteri (CVX), corpus uteri (CRP), not otherwise specified (NOS) uterus cancer and other very rare uterus cancer (OTH) mortality data were extracted from the WHO mortality database together with population data for Belgium and the Netherlands. Different ICD (International Classification of Diseases) were used over time for death cause certification. In the Netherlands, the proportion of not-otherwise specified uterine cancer deaths was small over large periods and therefore internal reallocation could be used to estimate the corrected rates cervical cancer mortality. In Belgium, the proportion of improperly defined uterus deaths was high. Therefore, the age-specific proportions of uterus cancer deaths that are probably of cervical origin for the Netherlands was applied to Belgian uterus cancer deaths to estimate the corrected number of cervix cancer deaths (corCVX). A Bayesian loglinear Poisson-regression model was performed to disentangle the separate effects of age, period and cohort. Results The corrected age standardized mortality rate (ASMR) decreased regularly from 9.2/100 000 in the mid 1950s to 2.5/100,000 in the late 1990s. Inclusion of age, period and cohort into the models were required to obtain an adequate fit. Cervical cancer mortality increases with age, declines over calendar period and varied irregularly by cohort. Conclusion Mortality increased with ageing and declined over time in most age-groups, but varied irregularly by birth cohort. In global, with some discrete exceptions, mortality decreased for successive generations up to the cohorts born in the 1930s. This decline stopped for cohorts born in the 1940s and thereafter. For the youngest cohorts, even a tendency of increasing risk of dying from cervical cancer could be observed, reflecting

Evolutive Masing model, cycling plasticity, ageing and memory effects

International Nuclear Information System (INIS)

Sidoroff, F.

1987-01-01

Many models are proposed for the mechanical description of the cyclic behaviour of metals and used for structure analysis under cyclic loading. The evolutive Masing model has been proposed (Fougeres, Sidoroff, Vincent and Waille 1985) to combine - the accuracy of hereditary models for the description of hysteresis on each cycle, - the versatility of internal variables for the state description and evolution, - a sufficient microstructural basis to make the interaction easier with microstructural investigations. The purpose of the present work is to discuss this model and to compare different evolution assumptions with respect to some memory effects (cyclic hardening and softening, multilevel tests, ageing). Attention is limited to uniaxial, rate independent elasto-plastic behaviour. (orig./GL)

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.

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

International Nuclear Information System (INIS)

Ward, Logan Timothy; Hackenberg, Robert Errol

2016-01-01

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.

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.

Uncertainty and sensitivity analyses for age-dependent unavailability model integrating test and maintenance

International Nuclear Information System (INIS)

Kančev, Duško; Čepin, Marko

2012-01-01

Highlights: ► Application of analytical unavailability model integrating T and M, ageing, and test strategy. ► Ageing data uncertainty propagation on system level assessed via Monte Carlo simulation. ► Uncertainty impact is growing with the extension of the surveillance test interval. ► Calculated system unavailability dependence on two different sensitivity study ageing databases. ► System unavailability sensitivity insights regarding specific groups of BEs as test intervals extend. - Abstract: The interest in operational lifetime extension of the existing nuclear power plants is growing. Consequently, plants life management programs, considering safety components ageing, are being developed and employed. Ageing represents a gradual degradation of the physical properties and functional performance of different components consequently implying their reduced availability. Analyses, which are being made in the direction of nuclear power plants lifetime extension are based upon components ageing management programs. On the other side, the large uncertainties of the ageing parameters as well as the uncertainties associated with most of the reliability data collections are widely acknowledged. This paper addresses the uncertainty and sensitivity analyses conducted utilizing a previously developed age-dependent unavailability model, integrating effects of test and maintenance activities, for a selected stand-by safety system in a nuclear power plant. The most important problem is the lack of data concerning the effects of ageing as well as the relatively high uncertainty associated to these data, which would correspond to more detailed modelling of ageing. A standard Monte Carlo simulation was coded for the purpose of this paper and utilized in the process of assessment of the component ageing parameters uncertainty propagation on system level. The obtained results from the uncertainty analysis indicate the extent to which the uncertainty of the selected

Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

Science.gov (United States)

Apfeld, Javier; Fontana, Walter

2017-12-23

It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

Modeling and analysis of aging behavior of concrete structures in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Rashid, J.Y.R.; James, R.J.; Dunham, R.S. [ANATECH (United States)

2011-07-01

As nuclear power plants approach the end of their original design life and begin to transition to the life extension phase, consideration has to be given to the effects of structural aging when evaluating the extended operation of reinforced or pre-stressed concrete structures. The behavior of concrete is highly nonlinear, having low tensile strength, shear stiffness and strength that depend on crack widths, and a confinement-dependent compressive elasto-plasticity. A concrete material model is described having the appropriate capabilities required for evaluating structural aging. The model treats reinforced concrete as a three-phase composite: plain concrete material as a three-dimensional continuum phase, steel reinforcement (rebar) as a uni-directional phase, and a rebar-concrete interaction phase. Structural aging is defined as the combined effects of time dependent material properties degradation and service induced changes in loading and operational conditions. Three broad categories of structural aging, and the interaction between them, are considered: 1) Aging effects due to expected time dependent changes in material properties, 2) Aging effects due to unexpected time dependent material degradation, and 3) Aging effects due to operational environment and loading. Example analyses are presented which illustrate the value of using advanced modeling and simulation in evaluating expected and unusual structural behavior. This is particularly important for safety structures that are approaching the end of their design life and are facing the prospect of re-licensing for extended operation

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Accounting for age uncertainty in growth modeling, the case study of yellowfin tuna (Thunnus albacares of the Indian Ocean.

Directory of Open Access Journals (Sweden)

Emmanuelle Dortel

Full Text Available Age estimates, typically determined by counting periodic growth increments in calcified structures of vertebrates, are the basis of population dynamics models used for managing exploited or threatened species. In fisheries research, the use of otolith growth rings as an indicator of fish age has increased considerably in recent decades. However, otolith readings include various sources of uncertainty. Current ageing methods, which converts an average count of rings into age, only provide periodic age estimates in which the range of uncertainty is fully ignored. In this study, we describe a hierarchical model for estimating individual ages from repeated otolith readings. The model was developed within a Bayesian framework to explicitly represent the sources of uncertainty associated with age estimation, to allow for individual variations and to include knowledge on parameters from expertise. The performance of the proposed model was examined through simulations, and then it was coupled to a two-stanza somatic growth model to evaluate the impact of the age estimation method on the age composition of commercial fisheries catches. We illustrate our approach using the sagittal otoliths of yellowfin tuna of the Indian Ocean collected through large-scale mark-recapture experiments. The simulation performance suggested that the ageing error model was able to estimate the ageing biases and provide accurate age estimates, regardless of the age of the fish. Coupled with the growth model, this approach appeared suitable for modeling the growth of Indian Ocean yellowfin and is consistent with findings of previous studies. The simulations showed that the choice of the ageing method can strongly affect growth estimates with subsequent implications for age-structured data used as inputs for population models. Finally, our modeling approach revealed particularly useful to reflect uncertainty around age estimates into the process of growth estimation and it can

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.

Carcinogen specific dosimetry model for passive smokers of various ages

International Nuclear Information System (INIS)

Robinson, Risa J.

2005-01-01

Studies indicate that being exposed to second hand smoke increases the chance of developing lung cancer. Understanding the deposition of carcinogenic particles present in second hand smoke is necessary to understand the development of specific histologic type cancers. In this study, a deposition model is presented for subjects of various ages exposed to sidestream smoke. The model included particle dynamics of coagulation, hygroscopic growth, charge and cloud behavior. Concentrations were varied from the maximum measured indoor concentrations (10 6 particles/cm 3 ) to what would be expected from wisps of smoke (10 8 particles/cm 3 ). Model results agreed well with experimental data taken from human subject deposition measurements (four studies). The model results were used to determine the dose intensity (dose per unit airway surface area) of Benzo[a]pyrene (BaP) in the respiratory tract for subjects of various ages. Model predictions for BaP surface concentration on the airway walls paralleled incident rates of tumors by location in the upper tracheobronchial region. Mass deposition efficiency was found to be larger for younger subjects, consistent with diffusion being the predominant mechanism for this particle size range. However, the actual dose intensity of BaP was found to be smaller for children than adults. This occurred due to the predominant effect of the smaller initial inhaled mass for children resulting from smaller tidal volumes. The resulting model is a useful tool to predict carcinogen specific particle deposition

The relative age effect in sport: a developmental systems model.

Science.gov (United States)

Wattie, Nick; Schorer, Jörg; Baker, Joseph

2015-01-01

The policies that dictate the participation structure of many youth sport systems involve the use of a set selection date (e.g. 31 December), which invariably produces relative age differences between those within the selection year (e.g. 1 January to 31 December). Those born early in the selection year (e.g. January) are relatively older—by as much as 12 months minus 1 day—than those born later in the selection year (e.g. December). Research in the area of sport has identified a number of significant developmental effects associated with such relative age differences. However, a theoretical framework that describes the breadth and complexity of relative age effects (RAEs) in sport does not exist in the literature. This paper reviews and summarizes the existing literature on relative age in sport, and proposes a constraints-based developmental systems model for RAEs in sport.

Stability analysis of nonlinear integro-differential equations arising in age-dependent epidemic models

International Nuclear Information System (INIS)

El Doma, M.

1995-05-01

An age-structured epidemic model of an SI type that incorporate vertical transmission is investigated when the fertility and mortality rates depend on age. We determine the steady states and examine their stabilities. (author). 13 refs

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.

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

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

Science.gov (United States)

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

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.

Mesoscopic model of temporal and spatial heterogeneity in aging colloids

DEFF Research Database (Denmark)

Becker, Nikolaj; Sibani, Paolo; Boettcher, Stefan

2014-01-01

We develop a simple and effective description of the dynamics of dense hard sphere colloids in the aging regime deep in the glassy phase. Our description complements the many efforts to understand the onset of jamming in low density colloids, whose dynamics is still time-homogeneous. Based...... scattering function and particle mean-square displacements for jammed colloidal systems, and we predict a growth for the peak of the χ4 mobility correlation function that is logarithmic in waiting-time. At the same time, our model suggests a novel unified description for the irreversible aging dynamics...

Crustal evolution in north-east and east Africa from model Nd ages

International Nuclear Information System (INIS)

Harris, N.B.W.; Hawkesworth, C.J.; Ries, A.C.

1984-01-01

The authors present the results of an Nd isotope study on the major rock units of the Pan-African (1,100-500 Myr BP) terrane. Charnockites from Jabel Uweinat, a basement inlier at the junction of Egypt, Libya and the Sudan, yield middle Archaean model Nd ages, whilst model ages of < 1,200 Myr have been obtained in a belt from the Eastern Desert of Egypt to north-west Kenya. Overall, the Pan-African rocks from north-east and east Africa and those from the Damara of Namibia exhibit a wide range of epsilonsub(Nd)(T) from +7.5 to -18.0 which reflects regional changes in tectonic style and is not readily reconciled with simple models for the evolution of average continental crust. (author)

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

International Nuclear Information System (INIS)

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

2009-01-01

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 230 Th- 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 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 3 O 8 ) may be assumed with confidence. We present here 230 Th- 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

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.

Modeling glass transition and aging processes in nanocomposites and polymer thin films

Science.gov (United States)

Pryamitsyn, Victor; Ganesan, Venkat

2010-03-01

We use a lattice kinetic model of glass transition to study the role of confinement and the presence of nano-inclusions. We have studied freely suspended films of glass-formers and its nanocomposites with ``plastifying'' and ``hardening'' nanoparticles. Using our model we determine the thickness and nanoparticle load dependencies of the Kauzmann temperature T0 and the fragility parameter. We found the glass transition temperature increases with the thickness of the film and the volume fraction of ``hardening'' nanoparticles , while Tg decreases with increase in the loading of ``plastifying'' nanoparticles. We found that the isothermal free volume relaxation rate of the nanocomposite thin film, usually referred as an aging, correlates with the glass transition temperature shift. We also studied the relations between our lattice model and Curro's, Kovacs and Struik's phenomenological models of free volume reduction to deduce physical insights into the mechanisms governing aging processes in thin films and nanocomposites.

Effort-reward imbalance and organisational injustice among aged nurses: a moderated mediation model.

Science.gov (United States)

Topa, Gabriela; Guglielmi, Dina; Depolo, Marco

2016-09-01

To test the effort-reward imbalance model among older nurses, expanding it to include the moderation of overcommitment and age in the stress-health complaints relationship, mediated by organisational injustice. The theoretical framework included the effort-reward imbalance, the uncertainty management and the socio-emotional selectivity models. Employing a two-wave design, the participants were 255 nurses aged 45 years and over, recruited from four large hospitals in Spain (Madrid and Basque Country). The direct effect of imbalance on health complaints was supported: it was significant when overcommitment was low but not when it was high. Organisational injustice mediated the influence of effort-reward imbalance on health complaints. The conditional effect of the mediation of organisational injustice was significant in three of the overcommitment/age conditions but it weakened, becoming non-significant, when the level of overcommitment was low and age was high. The study tested the model in nursing populations and expanded it to the settings of occupational health and safety at work. The results of this study highlight the importance of effort-reward imbalance and organisational justice for creating healthy work environments. © 2016 John Wiley & Sons Ltd.

Activated aging dynamics and effective trap model description in the random energy model

Science.gov (United States)

Baity-Jesi, M.; Biroli, G.; Cammarota, C.

2018-01-01

We study the out-of-equilibrium aging dynamics of the random energy model (REM) ruled by a single spin-flip Metropolis dynamics. We focus on the dynamical evolution taking place on time-scales diverging with the system size. Our aim is to show to what extent the activated dynamics displayed by the REM can be described in terms of an effective trap model. We identify two time regimes: the first one corresponds to the process of escaping from a basin in the energy landscape and to the subsequent exploration of high energy configurations, whereas the second one corresponds to the evolution from a deep basin to the other. By combining numerical simulations with analytical arguments we show why the trap model description does not hold in the former but becomes exact in the second.

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.

Science.gov (United States)

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes 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 (per)oxidation 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 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and 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.

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.

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...... the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important...

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

Anomalous scaling in an age-dependent branching model

OpenAIRE

Keller-Schmidt, Stephanie; Tugrul, Murat; Eguiluz, Victor M.; Hernandez-Garcia, Emilio; Klemm, Konstantin

2010-01-01

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...

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. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Forecasting selected specific age mortality rate of Malaysia by using Lee-Carter model

Science.gov (United States)

Shukri Kamaruddin, Halim; Ismail, Noriszura

2018-03-01

Observing mortality pattern and trend is an important subject for any country to maintain a good social-economy in the next projection years. The declining in mortality trend gives a good impression of what a government has done towards macro citizen in one nation. Selecting a particular mortality model can be a tricky based on the approached method adapting. Lee-Carter model is adapted because of its simplicity and reliability of the outcome results with approach of regression. Implementation of Lee-Carter in finding a fitted model and hence its projection has been used worldwide in most of mortality research in developed countries. This paper studies the mortality pattern of Malaysia in the past by using original model of Lee-Carter (1992) and hence its cross-sectional observation for a single age. The data is indexed by age of death and year of death from 1984 to 2012, in which are supplied by Department of Statistics Malaysia. The results are modelled by using RStudio and the keen analysis will focus on the trend and projection of mortality rate and age specific mortality rate in the future. This paper can be extended to different variants extensions of Lee-Carter or any stochastic mortality tool by using Malaysia mortality experience as a centre of the main issue.

Flexible parametric survival models built on age-specific antimüllerian hormone percentiles are better predictors of menopause.

Science.gov (United States)

Ramezani Tehrani, Fahimeh; Mansournia, Mohammad Ali; Solaymani-Dodaran, Masoud; Steyerberg, Ewout; Azizi, Fereidoun

2016-06-01

This study aimed to improve existing prediction models for age at menopause. We identified all reproductive aged women with regular menstrual cycles who met our eligibility criteria (n = 1,015) in the Tehran Lipid and Glucose Study-an ongoing population-based cohort study initiated in 1998. Participants were examined every 3 years and their reproductive histories were recorded. Blood levels of antimüllerian hormone (AMH) were measured at the time of recruitment. Age at menopause was estimated based on serum concentrations of AMH using flexible parametric survival models. The optimum model was selected according to Akaike Information Criteria and the realness of the range of predicted median menopause age. We followed study participants for a median of 9.8 years during which 277 women reached menopause and found that a spline-based proportional odds model including age-specific AMH percentiles as the covariate performed well in terms of statistical criteria and provided the most clinically relevant and realistic predictions. The range of predicted median age at menopause for this model was 47.1 to 55.9 years. For those who reached menopause, the median of the absolute mean difference between actual and predicted age at menopause was 1.9 years (interquartile range 2.9). The model including the age-specific AMH percentiles as the covariate and using proportional odds as its covariate metrics meets all the statistical criteria for the best model and provides the most clinically relevant and realistic predictions for age at menopause for reproductive-aged women.

New Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism

Directory of Open Access Journals (Sweden)

Claire J Foldi

2011-06-01

Full Text Available Offspring of older fathers have an increased risk of various adverse health outcomes, including autism and schizophrenia. With respect to biological mechanisms for this association, there are many more germline cell divisions in the life history of a sperm relative to that of an oocyte. This leads to more opportunities for copy error mutations in germ cells from older fathers. Evidence also suggests that epigenetic patterning in the sperm from older men is altered. Rodent models provide an experimental platform to examine the association between paternal age and brain development. Several rodent models of advanced paternal age (APA have been published with relevance to intermediate phenotypes related to autism. All four published APA models vary in key features creating a lack of consistency with respect to behavioural phenotypes. A consideration of common phenotypes that emerge from these APA-related mouse models may be informative in the exploration of the molecular and neurobiological correlates of APA.

Peroxide accumulation and cell death in filamentous fungi induced by contact with a contestant.

Science.gov (United States)

Silar, Philippe

2005-02-01

Podospora anserina and Coprinopsis cinerea (syn. Coprinus cinereus) are endowed with a defence system able to differentiate self vs. non-self and involving the generation of peroxide. Indeed, they produce peroxide when confronted with a filamentous fungus, only in non-self confrontations. Both species are not able to recognize yeasts and show a differential response to bacteria. The accumulation of peroxides in the ascomycete Podospora anserina requires an NADPH oxidase and a MAP kinase cascade, previously shown to be involved in fruit body formation, cell differentiation and cell degeneration. Confrontation is accompanied by the death of the contestant hyphae only in specific combinations of species. As in animals and plants, data suggest that peroxide is likely involved in signalling rather than playing a direct toxic role. Fungi display more complex behaviours than generally acknowledged, i.e. they are able to recognize potential contestants and built up defence reactions involving evolutionary conserved enzymes.

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.

A differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development.

Directory of Open Access Journals (Sweden)

Jörg Servos

Full Text Available The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS and of adenosine triphosphate (ATP. We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to

A Survival Model for Shortleaf Pine Tress Growing in Uneven-Aged Stands

Science.gov (United States)

Thomas B. Lynch; Lawrence R. Gering; Michael M. Huebschmann; Paul A. Murphy

1999-01-01

A survival model for shortleaf pine (Pinus echinata Mill.) trees growing in uneven-aged stands was developed using data from permanently established plots maintained by an industrial forestry company in western Arkansas. Parameters were fitted to a logistic regression model with a Bernoulli dependent variable in which "0" represented...

Prediction of battery storage ageing and solid electrolyte interphase property estimation using an electrochemical model

Science.gov (United States)

Ashwin, T. R.; Barai, A.; Uddin, K.; Somerville, L.; McGordon, A.; Marco, J.

2018-05-01

Ageing prediction is often complicated due to the interdependency of ageing mechanisms. Research has highlighted that storage ageing is not linear with time. Capacity loss due to storing the battery at constant temperature can shed more light on parametrising the properties of the Solid Electrolyte Interphase (SEI); the identification of which, using an electrochemical model, is systematically addressed in this work. A new methodology is proposed where any one of the available storage ageing datasets can be used to find the property of the SEI layer. A sensitivity study is performed with different molecular mass and densities which are key parameters in modelling the thickness of the SEI deposit. The conductivity is adjusted to fine tune the rate of capacity fade to match experimental results. A correlation is fitted for the side reaction variation to capture the storage ageing in the 0%-100% SoC range. The methodology presented in this paper can be used to predict the unknown properties of the SEI layer which is difficult to measure experimentally. The simulation and experimental results show that the storage ageing model shows good accuracy for the cases at 50% and 90% and an acceptable agreement at 20% SoC.

Modeling of system reliability Petri nets with aging tokens

International Nuclear Information System (INIS)

Volovoi, V.

2004-01-01

The paper addresses the dynamic modeling of degrading and repairable complex systems. Emphasis is placed on the convenience of modeling for the end user, with special attention being paid to the modeling part of a problem, which is considered to be decoupled from the choice of solution algorithms. Depending on the nature of the problem, these solution algorithms can include discrete event simulation or numerical solution of the differential equations that govern underlying stochastic processes. Such modularity allows a focus on the needs of system reliability modeling and tailoring of the modeling formalism accordingly. To this end, several salient features are chosen from the multitude of existing extensions of Petri nets, and a new concept of aging tokens (tokens with memory) is introduced. The resulting framework provides for flexible and transparent graphical modeling with excellent representational power that is particularly suited for system reliability modeling with non-exponentially distributed firing times. The new framework is compared with existing Petri-net approaches and other system reliability modeling techniques such as reliability block diagrams and fault trees. The relative differences are emphasized and illustrated with several examples, including modeling of load sharing, imperfect repair of pooled items, multiphase missions, and damage-tolerant maintenance. Finally, a simple implementation of the framework using discrete event simulation is described

Olfactory memory: a bridge between humans and animals in models of cognitive aging.

Science.gov (United States)

Eichenbaum, Howard; Robitsek, R Jonathan

2009-07-01

Odor-recognition memory in rodents may provide a valuable model of cognitive aging. In a recent study we used signal detection analyses to distinguish odor recognition based on recollection versus that based on familiarity. Aged rats were selectively impaired in recollection, with relative sparing of familiarity, and the deficits in recollection were correlated with spatial memory impairments. These results complement electrophysiological findings indicating age-associated deficits in the ability of hippocampal neurons to differentiate contextual information, and this information-processing impairment may underlie the common age-associated decline in olfactory and spatial memory.

Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

Science.gov (United States)

Delaney, M A; Kinsel, M J; Treuting, P M

2016-03-01

The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

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.

The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

Science.gov (United States)

Nkuipou-Kenfack, Esther; Schanstra, Joost P; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B; Rudolph, Karl L; Pich, Andreas; Mischak, Harald; Zürbig, Petra

2017-01-01

Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.

Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

International Nuclear Information System (INIS)

Killough, G.G.; Eckerman, K.F.

1986-01-01

This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. In most cases, the available data consisted of the patient's age at the time of administration, the patient's sex, the quantity of activity administered, the clinically-determined uptake of radioiodine by the thyroid, and the time after administration at which the uptake was determined. The metabolic model is of the form A(t) = K[exp(-μ 1 t) -exp(-μ 2 t)] (μCi), where μ 1 = λ/sub r/ - λ/sub i//sup b/ (i = 1, 2), λ/sub r/ is the radiological decay-rate coefficient, and λ/sub i//sup b/ are biological removal rate coefficients. The values of λ/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time or maximum uptake an the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptakes at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. 12 references, 5 figures, 5 tables

Using a micro-level model to generate a macro-level model of productive successful aging.

Science.gov (United States)

Johnson, Jessica K M; Sarkisian, Natalia; Williamson, John B

2015-02-01

Aging successfully entails good physical and cognitive health, as well as ongoing participation in social and productive activity. This study hones in on participation in productive activity, a factor that makes an important contribution to successful aging. One conceptual model of productive activity in later life specifies the antecedents and consequences of productivity. This study draws on that micro-level model to develop a corresponding macro-level model and assesses its utility for examining the predictors of and explaining the relationships between one form of productivity (labor force participation rates) and one aspect of well-being (average life expectancy) among males and females. Random effects regression models and path analysis were used to analyze cross-national longitudinal data for 24 high-income Organization for Economic Co-operation and Development (OECD) countries at seven time points (1980-2010; 168 observations total). OECD countries with higher labor force participation rates among older workers have higher life expectancies. Labor force participation mediates the effects of gross domestic product per capita on male and female life expectancy, and it mediates the effect of self-employment rate for men, but it acts as a suppressor with regard to the effect of public spending on male and female life expectancy. A well-known micro-level model of productive activity can be fruitfully adapted to account for macro-level cross-national variation in productivity and well-being. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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

International Nuclear Information System (INIS)

Tsai, Andy; Stamoulis, Catherine; Bixby, Sarah D.; Breen, Micheal A.; Connolly, Susan A.; Kleinman, Paul K.

2016-01-01

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.)

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.)

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.

Extraction and development of inset models in support of groundwater age calculations for glacial aquifers

Science.gov (United States)

Feinstein, Daniel T.; Kauffman, Leon J.; Haserodt, Megan J.; Clark, Brian R.; Juckem, Paul F.

2018-06-22

The U.S. Geological Survey developed a regional model of Lake Michigan Basin (LMB). This report describes the construction of five MODFLOW inset models extracted from the LMB regional model and their application using the particle-tracking code MODPATH to simulate the groundwater age distribution of discharge to wells pumping from glacial deposits. The five study areas of the inset model correspond to 8-digit hydrologic unit code (HUC8) basins. Two of the basins are tributary to Lake Michigan from the east, two are tributary to the lake from the west, and one is just west of the western boundary of the Lake Michigan topographic basin. The inset models inherited many of the inputs to the parent LMB model, including the hydrostratigraphy and layering scheme, the hydraulic conductivity assigned to bedrock layers, recharge distribution, and water use in the form of pumping rates from glacial and bedrock wells. The construction of the inset models entailed modifying some inputs, most notably the grid spacing (reduced from cells 5,000 feet on a side in the parent LMB model to 500 feet on a side in the inset models). The refined grid spacing allowed for more precise location of pumped wells and more detailed simulation of groundwater/surface-water interactions. The glacial hydraulic conductivity values, the top bedrock surface elevation, and the surface-water network input to the inset models also were modified. The inset models are solved using the MODFLOW–NWT code, which allows for more robust handling of conditions in unconfined aquifers than previous versions of MODFLOW. Comparison of the MODFLOW inset models reveals that they incorporate a range of hydrogeologic conditions relative to the glacial part of the flow system, demonstrated by visualization and analysis of model inputs and outputs and reflected in the range of ages generated by MODPATH for existing and hypothetical glacial wells. Certain inputs and outputs are judged to be candidate predictors that, if

Aging as Evolution-Facilitating Program and a Biochemical Approach to Switch It Off

Science.gov (United States)

Skulachev, Vladimir P.

decelerates the development of three types of accelerated aging (progeria) and also of normal aging, and this effect is especially demonstrative at early stages of aging. The same pattern is shown in invertebrates (Drosophila and Daphnia), and fungus (Podospora anserina). In mammals, the effect of SkQs on aging is accompanied by inhibition of development of such age-related diseases as osteoporosis, involution of thymus, cataract, retinopathy, etc. SkQ1 manifests a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision is recovered in 66 of 96 animals (dogs, cats and horses) who became blind because of retinopathy. SkQ1-containing drops instilled into eyes prevent the loss of sight in rabbits suffering from experimental uveitis and restore vision to animals that had already become blind due to this pathology. A favorable effect is also achieved in experimental glaucoma in rabbits. Moreover, the pretreatment of rats with 0.2 nM SkQ1 significantly decreases the H2O2-induced arrhythmia of the isolated heart. SkQ1 strongly reduces the damaged area in myocardial infarction or stroke and prevents the death of animals from kidney infarction. In p53-/- mice, SkQ1 decreases the ROS level in the spleen cells and inhibits appearance of lymphomas which are the main cause of death of such animals. As a result, the lifespan increases. SkQs look like promising drugs to treat aging and age-related diseases.

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

Science.gov (United States)

Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age

Collagen VI Null Mice as a Model for Early Onset Muscle Decline in Aging

Directory of Open Access Journals (Sweden)

Daniele Capitanio

2017-10-01

Full Text Available Collagen VI is an extracellular matrix (ECM protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius of wild-type and collagen VI null (Col6a1−/− mice at different ages, from 6- (adult to 12- (aged month-old to 24 (old month-old. While in wild-type animals the number of proteins and the level of modification occurring during aging were comparable in the two analyzed muscles, Col6a1−/− mice displayed a number of muscle-type specific variations. In particular, gastrocnemius displayed a limited number of dysregulated proteins in adult mice, while in aged muscles the modifications were more pronounced in terms of number and level. In diaphragm, the differences displayed by 6-month-old Col6a1−/− mice were more pronounced compared to wild-type mice and persisted at 12 months of age. In adult Col6a1−/− mice, the major variations were found in the enzymes belonging to the glycolytic pathway and the tricarboxylic acid (TCA cycle, as well as in autophagy-related proteins. When compared to wild-type animals Col6a1−/− mice displayed a general metabolic rewiring which was particularly prominent the diaphragm at 6 months of age. Comparison of the proteomic features and the molecular analysis of metabolic and autophagic pathways in adult and aged Col6a1−/− diaphragm indicated that the effects of aging, culminating in lipotoxicity and autophagic impairment, were already present at 6 months of age. Conversely, the effects of aging in Col6a1−/− gastrocnemius were similar but delayed becoming apparent at 12 months of age. A similar metabolic rewiring and autophagic impairment was found in the diaphragm of 24-month-old wild-type mice, confirming that fatty acid synthase (FASN increment and

Project-oriented teaching model about specialized courses in the information age

Science.gov (United States)

Chen, Xiaodong; Wang, Jinjiang; Tian, Qingguo; Wang, Yi; Cai, Huaiyu

2017-08-01

Specialized courses play a significant role in the usage of basic knowledge in the practical application for engineering college students. The engineering data available has sharply increased since the beginning of the information age in the 20th century, providing much more approaches to study and practice. Therefore, how to guide students to make full use of resources for active engineering practice learning has become one of the key problems for specialized courses. This paper took the digital image processing course for opto-electronic information science and technology major as an example, discussed the teaching model of specialized course in the information age, put forward the "engineering resource oriented model", and fostered the ability of engineering students to use the basic knowledge to innovate and deal with specific project objectives. The fusion of engineering examples into practical training and teaching encourages students to practice independent engineering thinking.

Constitutive modelling of creep-ageing behaviour of peak-aged aluminium alloy 7050

Directory of Open Access Journals (Sweden)

Yang Yo-Lun

2015-01-01

Full Text Available The creep-ageing behaviour of a peak-aged aluminium alloy 7050 was investigated under different stress levels at 174 ∘C for up to 8 h. Interrupted creep tests and tensile tests were performed to investigate the influences of creep-ageing time and applied stress on yield strength. The mechanical testing results indicate that the material exhibits an over-ageing behaviour which increases with the applied stress level during creep-ageing. As creep-ageing time approaches 8 h, the material's yield strength under different stress levels gradually converge, which suggests that the difference in mechanical properties under different stress conditions can be minimised. This feature can be advantageous in creep-age forming to the formed components such that uniformed mechanical properties across part area can be achieved. A set of constitutive equations was calibrated using the mechanical test results and the alloy-specific material constants were obtained. A good agreement is observed between the experimental and calibrated results.

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.

Quantification the Effect of Ageing on Characteristics of the Photoplethysmogram Using an Optimized Windkessel Model

Directory of Open Access Journals (Sweden)

Doostdar H.

2014-09-01

Full Text Available Background: With increasing age, some changes appeared in specifications of vessels which including dimensions and elasticity in theirs. The changes in parameters such as resistance, inertance and compliance vessels appear and eventually changes in the environmental pulse releases are in circulation. These changes clearly appear in specification of photoplethysmogram particularly in the size and position signals second peak is observed. Aim and scope: The aim of study was to Circulatory system modeling using windkessel electrical model for evalution blood flow and Its matching with the photoplethysmogram’s signal for investigate the reasons for changes of Characteristics of the Photoplethysmogram. The first purpose of this paper is to examine the age-related parameters in the Photoplethysmogram’s signal and finally the diagnosis of cardiovascular disease using the model and photoplethysmogram’s signal. Methods: In this study we followed some of these effects to the circulatory system by using the windkessel electrical model. The algorithm in this project appeared by optimization with the matrix coefficients of state space windkessel electrical model. Optimize of the coefficients matching with the output of the model and the photoplethysmogram’s signal. Photoplethysmogram’s signals from 50 healthy subjects with the age range of 20 to 50 years, shows that outputs the model and photoplethysmogram’s signal in terms of error rate and cross-correlation algorithm in a fully automate, was consistent. Wavelength of the Photoplethysmogram’s signals were 950 nm and The sampling rate was set at 50 Hz. Results: Simulation results show that aging reduces the signal amplitude and delay of the second peak occurs. These changes were seen as reduce the rate of compliance and increase the rate of resistance and inertance windkessel electrical model of circulation. Conclusion: The high accuracy of the results led to being able to identify the age

Understanding the link between sexual selection, sexual conflict and aging using crickets as a model.

Science.gov (United States)

Archer, C Ruth; Hunt, John

2015-11-01

Aging evolved because the strength of natural selection declines over the lifetime of most organisms. Weak natural selection late in life allows the accumulation of deleterious mutations and may favor alleles that have positive effects on fitness early in life, but costly pleiotropic effects expressed later on. While this decline in natural selection is central to longstanding evolutionary explanations for aging, a role for sexual selection and sexual conflict in the evolution of lifespan and aging has only been identified recently. Testing how sexual selection and sexual conflict affect lifespan and aging is challenging as it requires quantifying male age-dependent reproductive success. This is difficult in the invertebrate model organisms traditionally used in aging research. Research using crickets (Orthoptera: Gryllidae), where reproductive investment can be easily measured in both sexes, has offered exciting and novel insights into how sexual selection and sexual conflict affect the evolution of aging, both in the laboratory and in the wild. Here we discuss how sexual selection and sexual conflict can be integrated alongside evolutionary and mechanistic theories of aging using crickets as a model. We then highlight the potential for research using crickets to further advance our understanding of lifespan and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Keep Up the Good Work! Age-Moderated Mediation Model on Intention to Retire

Directory of Open Access Journals (Sweden)

Paola Dordoni

2017-10-01

Full Text Available In European nations, the aging of the workforce is a major issue which is increasingly addressed both in national and organizational policies in order to sustain older workers' employability and to encourage longer working lives. Particularly older workers' employability can be viewed an important issue as this has the potential to motivate them for their work and change their intention to retire. Based on lifespan development theories and Van der Heijden's ‘employability enhancement model’, this paper develops and tests an age-moderated mediation model (which refers to the processes that we want to test in this model, linking older workers' (55 years old and over perceptions of job support for learning (job-related factor and perceptions of negative age stereotypes on productivity (organizational factor, on the one hand, and their intention to retire, on the other hand, via their participation in employability enhancing activities, being the mediator in our model. A total of 2,082 workers aged 55 years and above were included in the analyses. Results revealed that the two proposed relationships between the predictors and intention to retire were mediated by participation in employability enhancing activities, reflecting two mechanisms through which work context affects intention to retire (namely ‘a gain spiral and a loss spiral’. Multi-Group SEM analyses, distinguishing between two age groups (55–60 and 61–65 years old, revealed different paths for the two distinguished groups of older workers. Employability mediated the relationship between perceptions of job support for learning and intention to retire in both age groups, whereas it only mediated the relationship between perceptions of negative age stereotypes and intention to retire in the 55–60 group. From our empirical study, we may conclude that employability is an important factor in the light of older workers' intention to retire. In order to motivate this category of

Weak temperature dependence of ageing of structural properties in atomistic model glassformers

Science.gov (United States)

Jenkinson, Thomas; Crowther, Peter; Turci, Francesco; Royall, C. Patrick

2017-08-01

Ageing phenomena are investigated from a structural perspective in two binary Lennard-Jones glassformers, the Kob-Andersen and Wahnström mixtures. In both, the geometric motif assumed by the glassformer upon supercooling, the locally favoured structure (LFS), has been established. The Kob-Andersen mixture forms bicapped square antiprisms; the Wahnström model forms icosahedra. Upon ageing, we find that the structural relaxation time has a time-dependence consistent with a power law. However, the LFS population and potential energy increase and decrease, respectively, in a logarithmic fashion. Remarkably, over the time scales investigated, which correspond to a factor of 104 change in relaxation times, the rate at which these quantities age appears almost independent of temperature. Only at temperatures far below the Vogel-Fulcher-Tamman temperature do the ageing dynamics slow.

Evolution of the rate of biological aging using a phenotype based computational model.

Science.gov (United States)

Kittas, Aristotelis

2010-10-07

In this work I introduce a simple model to study how natural selection acts upon aging, which focuses on the viability of each individual. It is able to reproduce the Gompertz law of mortality and can make predictions about the relation between the level of mutation rates (beneficial/deleterious/neutral), age at reproductive maturity and the degree of biological aging. With no mutations, a population with low age at reproductive maturity R stabilizes at higher density values, while with mutations it reaches its maximum density, because even for large pre-reproductive periods each individual evolves to survive to maturity. Species with very short pre-reproductive periods can only tolerate a small number of detrimental mutations. The probabilities of detrimental (P(d)) or beneficial (P(b)) mutations are demonstrated to greatly affect the process. High absolute values produce peaks in the viability of the population over time. Mutations combined with low selection pressure move the system towards weaker phenotypes. For low values in the ratio P(d)/P(b), the speed at which aging occurs is almost independent of R, while higher values favor significantly species with high R. The value of R is critical to whether the population survives or dies out. The aging rate is controlled by P(d) and P(b) and the amount of the viability of each individual is modified, with neutral mutations allowing the system more "room" to evolve. The process of aging in this simple model is revealed to be fairly complex, yielding a rich variety of results. 2010 Elsevier Ltd. All rights reserved.

The relevance of parametric U-uptake models in ESR age calculations

International Nuclear Information System (INIS)

Gruen, Rainer

2009-01-01

In the ESR dating three basic parametric U-uptake models have been applied for dating teeth: early U-uptake (EU: closed system), linear U-uptake (LU) and recent U-uptake (RU, it is assumed that the dose rate contribution of U in the dental tissues is zero). In many ESR dating publications it is still assumed that samples comply with one or the other parametric U-uptake model calculation or that their correct age lies somewhere between EU and LU. Observations of the spatial distribution of uranium in dental tissues show that it is difficult to predict any relationships between the relative uptake in the dental tissues. Combined U-series/ESR age estimates can give insights into the actual U-uptake. An evaluation of published data shows that for cave sites, a significant number of results fall outside the EU and LU bracket, while for open air sites, the majority of data are outside this bracket, particularly showing greatly delayed U-uptake. This may be due to changes in the hydrological system, leading to erosion which exposes the open air site. U-leaching has also been observed on samples from open air sites, in which case any reasonable age calculation is impossible.

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.

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.

Priming of microglia in a DNA-repair deficient model of accelerated aging.

Science.gov (United States)

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

2014-09-01

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 microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state. Copyright © 2014 Elsevier Inc. All rights reserved.

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. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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�

Bacteria as a new model system for aging studies: investigations using light microscopy.

Science.gov (United States)

Ackermann, Martin

2008-04-01

Aging-the decline in an individual's condition over time-is at the center of an active research field in medicine and biology. Some very basic questions have, however, remained unresolved, the most fundamental being: do all organisms age? Or are there organisms that would continue to live forever if not killed by external forces? For a long time it was believed that aging only affected organisms such as animals, plants, and fungi. Bacteria, in contrast, were assumed to be potentially immortal and until recently this assertion remained untested. We used phase-contrast microscopy (on an Olympus BX61) to follow individual bacterial cells over many divisions to prove that some bacteria show a distinction between an aging mother cell and a rejuvenated daughter, and that these bacteria thus age. This indicates that aging is a more fundamental property of organisms than was previously assumed. Bacteria can now be used as very simple model system for investigating why and how organisms age.

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

Mixture modeling of multi-component data sets with application to ion-probe zircon ages

Science.gov (United States)

Sambridge, M. S.; Compston, W.

1994-12-01

A method is presented for detecting multiple components in a population of analytical observations for zircon and other ages. The procedure uses an approach known as mixture modeling, in order to estimate the most likely ages, proportions and number of distinct components in a given data set. Particular attention is paid to estimating errors in the estimated ages and proportions. At each stage of the procedure several alternative numerical approaches are suggested, each having their own advantages in terms of efficency and accuracy. The methodology is tested on synthetic data sets simulating two or more mixed populations of zircon ages. In this case true ages and proportions of each population are known and compare well with the results of the new procedure. Two examples are presented of its use with sets of SHRIMP U-238 - Pb-206 zircon ages from Palaeozoic rocks. A published data set for altered zircons from bentonite at Meishucun, South China, previously treated as a single-component population after screening for gross alteration effects, can be resolved into two components by the new procedure and their ages, proportions and standard errors estimated. The older component, at 530 +/- 5 Ma (2 sigma), is our best current estimate for the age of the bentonite. Mixture modeling of a data set for unaltered zircons from a tonalite elsewhere defines the magmatic U-238 - Pb-206 age at high precision (2 sigma +/- 1.5 Ma), but one-quarter of the 41 analyses detect hidden and significantly older cores.

A Proactive Aging/Asset Management Model to Optimize Equipment Maintenance Resources Over Plant Lifetime

International Nuclear Information System (INIS)

Meyer, Theodore A.; Perdue, Robert K.; Woodcock, Joel; Elder, G. Gary

2002-01-01

Experience has shown that proactive aging/asset management can best be defined as an ongoing process. Station goals directly supported by such a process include reducing Unplanned Capability Loss Factor and gaining the optimum value from maintenance and aging management budgets. An effective aging/asset management process must meet evolving and sometimes conflicting requirements for efficient and reliable nuclear power plant operation. The process should identify most likely contributors before they fail, and develop cost-effective contingencies. Current trends indicate the need for focused tools that give quantitative input to decision-making. Opposing goals, such as increasing availability while optimizing aging management budgets, must be balanced. Recognizing the importance of experience in reducing the uncertainty inherent in predicting equipment degradation rates, nuclear industry demographics suggest the need to capture existing expert knowledge in a usable form. The Proactive Aging/Asset Management Process has been developed to address these needs. The proactive approach is a process supported by tools. The process identifies goals and develops criteria - including safety, costs, and power production - that are used to prioritize systems and equipment across the plant. The process then draws upon tools to most effectively meet the plant's goals. The Proactive Aging/Asset Management Model TM is one software-enabled tool designed for mathematical optimization. Results assist a plant in developing a plant-wide plan of aging management activities. This paper describes the proactive aging/asset management process and provides an overview of the methodology that has been incorporated in a model to perform a plant-wide optimization of aging management activities. (authors)

Modeling mangrove biomass using remote sensing based age and growth estimates

Science.gov (United States)

Lagomasino, D.; Fatoyinbo, T. E.; Feliciano, E. A.; Lee, S. K.; Trettin, C.; Mangora, M.; Rahman, M.

2016-12-01

Mangroves are highly regarded coastal forests because of their ecosystem services and high carbon storage potential. In addition, these forests can develop rapidly in locations where congenial environmental conditions and sediment supply are available. Monitoring the growth and age of developing mangrove forests is crucial for sustainable management and estimating carbon stocks. Combining imagery from radar and optical satellites (e.g., TanDEM-X and Landsat), we can estimate young mangrove growth and age at regional and continental scales. We used TanDEM-X radar interferometry for modeling canopy height in 2013 and Landsat to measure land cover change from 1990 to 2013. Annual NDVI composites were determined for each calendar year between 1990 and 2013. New land areas gained from the transition of water to vegetation were determined by the differences in annual NDVI composites and the reference year 2013. The year of the greatest NDVI difference that met the threshold criteria was used as the initial tree height (0 m). Annual canopy height growth rates were estimated by the duration between land generation times and 2013 canopy height models derived from TanDEM-X and very-high resolution optical data. In this presentation, we compare growth rates and biomass accumulation in mangrove forests at four river deltas; the Zambezi (Mozambique), Rufiji (Tanzania), Ganges (Bangladesh), and Mekong (Vietnam). The spatial patterns of growth rates coincided with characteristic successional paradigms and stream morphology, where the maximum growth rates typically occurred along prograding creek banks. Initial comparisons between height-only and growth-age biomass indicate that the latter tend to overestimate biomass for younger forest stands of similar height. Both the vertical (e.g., canopy height) and horizontal (e.g., expansion) growth rates measured from remote sensing can garner important information regarding mangrove succession and primary productivity. Continued research

Rate and State Friction Relation for Nanoscale Contacts: Thermally Activated Prandtl-Tomlinson Model with Chemical Aging

Science.gov (United States)

Tian, Kaiwen; Goldsby, David L.; Carpick, Robert W.

2018-05-01

Rate and state friction (RSF) laws are widely used empirical relationships that describe macroscale to microscale frictional behavior. They entail a linear combination of the direct effect (the increase of friction with sliding velocity due to the reduced influence of thermal excitations) and the evolution effect (the change in friction with changes in contact "state," such as the real contact area or the degree of interfacial chemical bonds). Recent atomic force microscope (AFM) experiments and simulations found that nanoscale single-asperity amorphous silica-silica contacts exhibit logarithmic aging (increasing friction with time) over several decades of contact time, due to the formation of interfacial chemical bonds. Here we establish a physically based RSF relation for such contacts by combining the thermally activated Prandtl-Tomlinson (PTT) model with an evolution effect based on the physics of chemical aging. This thermally activated Prandtl-Tomlinson model with chemical aging (PTTCA), like the PTT model, uses the loading point velocity for describing the direct effect, not the tip velocity (as in conventional RSF laws). Also, in the PTTCA model, the combination of the evolution and direct effects may be nonlinear. We present AFM data consistent with the PTTCA model whereby in aging tests, for a given hold time, static friction increases with the logarithm of the loading point velocity. Kinetic friction also increases with the logarithm of the loading point velocity at sufficiently high velocities, but at a different increasing rate. The discrepancy between the rates of increase of static and kinetic friction with velocity arises from the fact that appreciable aging during static contact changes the energy landscape. Our approach extends the PTT model, originally used for crystalline substrates, to amorphous materials. It also establishes how conventional RSF laws can be modified for nanoscale single-asperity contacts to provide a physically based friction

Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold

NARCIS (Netherlands)

Daskalov, A.; Habenstein, B.; Martinez, D.; Debets, A.J.M.; Sabate, R.; Loquet, A.; Saupe, S.J.

2015-01-01

In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s ß-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S

Results from a new mathematical model of gastrointestinal transit that incorporates age and gender-dependent physiological parameters

International Nuclear Information System (INIS)

Stubbs, J.B.

1992-01-01

Recently published data on effects of age and gender-dependent GI physiology and motility have been used to develop a new mathematical model describing the transit and adsorption of substances through the GI tract. This mathematical description of GI tract kinetics utilises more physiologically accurate transit processes than the ICRP Report 30 GI model. The model uses a combination of zero and first-order kinetics to describe motility. Some of the physiological parameters that the new model uses are gender, age, phase of the menstrual cycle, meal composition and gastric phase (solid versus liquid). A computer algorithm based on this model has been derived and results for young males are compared to those of the ICRP 30 model. Comparison of gastrointestinal residence times for 99 Tc m and 111 In labelled compounds, as a function of gender and age, are also presented. (author)

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. Copyright © 2015, American Association for the Advancement of Science.

End-of-Discharge and End-of-Life Prediction in Lithium-Ion Batteries with Electrochemistry-Based Aging Models

Science.gov (United States)

Daigle, Matthew; Kulkarni, Chetan S.

2016-01-01

As batteries become increasingly prevalent in complex systems such as aircraft and electric cars, monitoring and predicting battery state of charge and state of health becomes critical. In order to accurately predict the remaining battery power to support system operations for informed operational decision-making, age-dependent changes in dynamics must be accounted for. Using an electrochemistry-based model, we investigate how key parameters of the battery change as aging occurs, and develop models to describe aging through these key parameters. Using these models, we demonstrate how we can (i) accurately predict end-of-discharge for aged batteries, and (ii) predict the end-of-life of a battery as a function of anticipated usage. The approach is validated through an experimental set of randomized discharge profiles.

A goods characteristics model of the hedonic ageing equation: evidence from a French marriage bureau

OpenAIRE

Sam Cameron; Nicolas Vaillant

2005-01-01

The present paper adopts a modelling perspective derived from goods characteristics analysis [Lancaster (1971)] and the general ideas of transactions costs. This is implemented in estimated equations, which feature the age of partner sought as the dependent variable and own age and various other personal characteristics, and characteristics desired in a partner, as the right-hand side variables. The results show a very strong relationship between age and desired partner age. More interestingl...

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.

Beyond 'doing': Supporting clinical leadership and nursing practice in aged care through innovative models of care.

Science.gov (United States)

Venturato, Lorraine; Drew, Liz

2010-06-01

Contemporary health care environments are increasingly challenged by issues associated with the recruitment and retention of qualified nursing staff. This challenge is particularly felt by residential aged care providers, with registered nurse (RN) numbers already limited and resident acuity rapidly rising. As a result, aged care service providers are increasingly exploring creative and alternative models of care. This article details exploratory research into a pre-existing, alternative model of care in a medium sized, regional residential aged care facility. Research findings suggest that the model of care is complex and multi-faceted and is an example of an integrated model of care. As a result of the implementation of this model of care a number of shifts have occurred in the practice experiences and clinical culture within this facility. Results suggest that the main benefits of this model are: (1) increased opportunities for RNs to engage in clinical leadership and proactive care management; (2) improved management and communication in relation to work processes and practices; and (3) enhanced recruitment and retention of both RNs and care workers.

Forecasting Trends in Disability in a Super-Aging Society: Adapting the Future Elderly Model to Japan

Science.gov (United States)

Chen, Brian K.; Jalal, Hawre; Hashimoto, Hideki; Suen, Sze-chuan; Eggleston, Karen; Hurley, Michael; Schoemaker, Lena; Bhattacharya, Jay

2016-01-01

Japan has experienced pronounced population aging, and now has the highest proportion of elderly adults in the world. Yet few projections of Japan’s future demography go beyond estimating population by age and sex to forecast the complex evolution of the health and functioning of the future elderly. This study estimates a new state-transition microsimulation model – the Japanese Future Elderly Model (FEM) – for Japan. We use the model to forecast disability and health for Japan’s future elderly. Our simulation suggests that by 2040, over 27 percent of Japan’s elderly will exhibit 3 or more limitations in IADLs and social functioning; almost one in 4 will experience difficulties with 3 or more ADLs; and approximately one in 5 will suffer limitations in cognitive or intellectual functioning. Since the majority of the increase in disability arises from the aging of the Japanese population, prevention efforts that reduce age-specific morbidity can help reduce the burden of disability but may have only a limited impact on reducing the overall prevalence of disability among Japanese elderly. While both age and morbidity contribute to a predicted increase in disability burden among elderly Japanese in the future, our simulation results suggest that the impact of population aging exceeds the effect of age-specific morbidity on increasing disability in Japan’s future. PMID:28580275

Stability analysis of a general age-dependent vaccination model of a vertically transmitted disease

International Nuclear Information System (INIS)

El Doma, M.

1995-07-01

An SIR epidemic model of a general age-dependent vaccination of a vertically as well as horizontally transmitted disease is investigated when the population is in steady state and the fertility, mortality and removal rates depends on age. We determine the steady states and examine their stabilities. (author). 24 refs

Combining an Electrothermal and Impedance Aging Model to Investigate Thermal Degradation Caused by Fast Charging

Directory of Open Access Journals (Sweden)

Joris de Hoog

2018-03-01

Full Text Available Fast charging is an exciting topic in the field of electric and hybrid electric vehicles (EVs/HEVs. In order to achieve faster charging times, fast-charging applications involve high-current profiles which can lead to high cell temperature increase, and in some cases thermal runaways. There has been some research on the impact caused by fast-charging profiles. This research is mostly focused on the electrical, thermal and aging aspects of the cell individually, but these factors are never treated together. In this paper, the thermal progression of the lithium-ion battery under specific fast-charging profiles is investigated and modeled. The cell is a Lithium Nickel Manganese Cobalt Oxide/graphite-based cell (NMC rated at 20 Ah, and thermal images during fast-charging have been taken at four degradation states: 100%, 90%, 85%, and 80% State-of-Health (SoH. A semi-empirical resistance aging model is developed using gathered data from extensive cycling and calendar aging tests, which is coupled to an electrothermal model. This novel combined model achieves good agreement with the measurements, with simulation results always within 2 °C of the measured values. This study presents a modeling methodology that is usable to predict the potential temperature distribution for lithium-ion batteries (LiBs during fast-charging profiles at different aging states, which would be of benefit for Battery Management Systems (BMS in future thermal strategies.

Risk, reward, and decision-making in a rodent model of cognitive aging

Directory of Open Access Journals (Sweden)

Ryan J Gilbert

2012-01-01

Full Text Available Impaired decision-making in aging can directly impact factors (financial security, quality of healthcare that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5-7 mo. and aged (23-25 mo. male F344 rats were trained on a probability discounting task in which they made discrete-trial choices between a small certain reward (1 food pellet and a large but uncertain reward (2 food pellets with varying probabilities of delivery ranging from 100% to 0%. Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the smaller but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for costs (i.e., delay, probability. These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct neural mechanisms that can impact cost

Risk, reward, and decision-making in a rodent model of cognitive aging.

Science.gov (United States)

Gilbert, Ryan J; Mitchell, Marci R; Simon, Nicholas W; Bañuelos, Cristina; Setlow, Barry; Bizon, Jennifer L

2011-01-01

Impaired decision-making in aging can directly impact factors (financial security, health care) that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5-7 months) and aged (23-25 months) male F344 rats were trained on a probability discounting task in which they made discrete-trial choices between a small certain reward (one food pellet) and a large but uncertain reward (two food pellets with varying probabilities of delivery ranging from 100 to 0%). Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the small but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was also certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for reward costs (i.e., delay or probability). These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct mechanisms that can impact cost-benefit decision-making.

Results from a new mathematical model of gastrointestinal transit that incorporates age and gender-dependent physiological parameters

Energy Technology Data Exchange (ETDEWEB)

Stubbs, J B [Oak Ridge Associated Universities, Inc., TN (United States). Medical and Health Science Div.

1992-01-01

Recently published data on effects of age and gender-dependent GI physiology and motility have been used to develop a new mathematical model describing the transit and adsorption of substances through the GI tract. This mathematical description of GI tract kinetics utilises more physiologically accurate transit processes than the ICRP Report 30 GI model. The model uses a combination of zero and first-order kinetics to describe motility. Some of the physiological parameters that the new model uses are gender, age, phase of the menstrual cycle, meal composition and gastric phase (solid versus liquid). A computer algorithm based on this model has been derived and results for young males are compared to those of the ICRP 30 model. Comparison of gastrointestinal residence times for {sup 99}Tc{sup m} and {sup 111}In labelled compounds, as a function of gender and age, are also presented. (author).

Variance Components Models for Physical Activity With Age as Modifier: A Comparative Twin Study in Seven Countries

NARCIS (Netherlands)

Vink, J.M.; Boomsma, D.I.; Medland, S.E.; Moor, H.M. de; Stubbe, J.H.; Corner, B.K.; Martin, N.G.; Skytthea, A.; Kyvik, K.O.; Rose, R..J.; Kujala, U.M.; Kaprio, J.; Harris, J.R.; Pedersen, N.L.; Cherkas, L.; Spector, T.D.; Geus, E.J.

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

Modeling age differences in effects of pair repetition and proactive interference using a single parameter.

Science.gov (United States)

Stephens, Joseph D W; Overman, Amy A

2018-02-01

In this article, we apply the REM model (Shiffrin & Steyvers, 1997) to age differences in associative memory. Using Criss and Shiffrin's (2005) associative version of REM, we show that in a task with pairs repeated across 2 study lists, older adults' reduced benefit of pair repetition can be produced by a general reduction in the diagnosticity of information stored in memory. This reduction can be modeled similarly well by reducing the overall distinctiveness of memory features, or by reducing the accuracy of memory encoding. We report a new experiment in which pairs are repeated across 3 study lists and extend the model accordingly. Finally, we extend the model to previously reported data using the same task paradigm, in which the use of a high-association strategy introduced proactive interference effects in young adults but not older adults. Reducing the diagnosticity of information in memory also reduces the proactive interference effect. Taken together, the modeling and empirical results reported here are consistent with the claim that some age differences that appear to be specific to associative information can be produced via general degradation of information stored in memory. The REM model provides a useful framework for examining age differences in memory as well as harmonizing seemingly conflicting prior modeling approaches for the associative deficit. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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; Njeuhmeli, Emmanuel

2016-01-01

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.

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.

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

KAUST Repository

Korobeinikov, Andrei; Melnik, Andrey V.

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.

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.

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.

Study and prediction model on low temperature aging embrittlement in duplex stainless steels

International Nuclear Information System (INIS)

Sanchez, L.; Gutierrez-Solana, F.

1997-01-01

Within the framework of a general study on low temperature (280-400 degree centigree) aging embrittlement in duplex stainless steels, a relationship has been obtained between aging, measured from ferrite hardness evolution, and bulk materials embrittlement, determined from fracture toughness and fracture impact tests. The existing correlation between the increase in ferrite hardness and its percentage presence in the fracture path supports this relationship and results in the development of a prediction design model which provides the fracture resistance curves, for any aging level, based on the chemical composition and the steel's properties in an unaged state. (Author)

Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease

DEFF Research Database (Denmark)

Diaz, Ricardo Gredilla; Weissman, Lior; Yang, JL

2012-01-01

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...... 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...

A new mathematical model of gastrointestinal transit incorporating age- and gender-dependent physiological parameters

International Nuclear Information System (INIS)

Stubbs, J.B.

1992-01-01

As part of the revision by the International Commission on Radiological Protection (ICRP) of its report on Reference Man, an extensive review of the literature regarding anatomy and morphology of the gastrointestinal (GI) tract has been completed. Data on age- and gender-dependent GI physiology and motility may be included in the proposed ICRP report. A new mathematical model describing the transit of substances through the GI tract as well as the absorption and secretion of material in the GI tract has been developed. This mathematical description of GI tract kinetics utilizes more physiologically accurate transit processes than the mathematically simple, but nonphysiological, GI tract model that was used in ICRP Report 30. The proposed model uses a combination of zero- and first-order kinetics to describe motility. Some of the physiological parameters that the new model accounts for include sex, age, pathophysiological condition and meal phase (solid versus liquid). A computer algorithm, written in BASIC, based on this new model has been derived and results are compared to those of the ICRP-30 model

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

Science.gov (United States)

2016-01-01

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. PMID:27051508

Skull Thickness Morphing for an Age and Sex Specific FE Model of the Skull.

Science.gov (United States)

Jones, Derek A; Urban, Jillian E; Lillie, Elizabeth M; Stitzel, Joel D

2015-01-01

Skull deformation is believed to be a contributing factor in traumatic brain injury (TBI). Furthermore, skull thickness is thought to be an important factor governing deformation of the skull and its susceptibility to fracture. Although many studies have been done to understand the mechanisms of brain injury and skull fracture, the majority of the cadaveric and finite element (FE) modeling efforts are comprised of older males and 50th percentile male skulls, respectively, which do not accurately represent the population as a whole. This study employed a set of skull table thickness regressions defined at homologous landmarks on the skull which were calculated from 123 pre-existing head CT scans (ages 20-100) using a cortical density-based algorithm. A method was developed to morph the Global Human Body Models Consortium (GHBMC) 50th percentile male skull model to age and gender specific geometries based on the full thickness regressions using a Thin Plate Spline algorithm. A quantitative measure of morphing error was devised and measured using the morphed and desired full thickness values at the homologous landmark locations. This methodology can be used to create gender and age-specific FE models of the skull and will ultimately be used to understand the relationship between cortical thickness, skull deformation, and head injury.

Sensory perception and aging in model systems: from the outside in.

Science.gov (United States)

Linford, Nancy J; Kuo, Tsung-Han; Chan, Tammy P; Pletcher, Scott D

2011-01-01

Sensory systems provide organisms from bacteria to humans with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organismal lifespan, have opened the door for powerful new research into aging. Although direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging.

Transplanted Adipose-Derived Stem Cells Ameliorate Testicular Dysfunction In A D-Galactose-Induced Aging Rat Model.

Science.gov (United States)

Yang, Chun; Du, Yi-Kuan; Wang, Jun; Luan, Ping; Yang, Qin-Lao; Huang, Wen-Hua; Yuan, Lin

2015-10-01

Glycation product accumulation during aging of slowly renewing tissues may be an important mechanism underlying aging of the testis. Adipose-derived stem cells (ADSCs) have shown promise in a novel tissue regenerative technique and may have utility in treating sexual dysfunction. ADSCs have also been found to be effective in antiaging therapy, although the mechanism underlying their effects remains unknown. This study was designed to investigate the anti-aging effect of ADSCs in a D-galactose (D-gal)-induced aging animal model and to clarify the underlying mechanism. Randomly selected 6-week-old male Sprague-Dawley rats were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, D-gal-induced aging rats were randomized to receive caudal vein injections of 3 × 10(6) 5-bromo 2'deoxy-uridine-labeled ADSCs or an equal volume of phosphate-buffered saline. Serum testosterone level, steroidogenic enzymes (3-β-hydroxysteroid dehydrogenase), and superoxide dismutase (SOD) activity decreased significantly in aging rats compared with the control group; serum lipid peroxidation, spermatogenic cell apoptosis, and methane dicarboxylic aldehyde (MDA) expression increased significantly. ADSCs increased the SOD level and reduced the MDA level in the aging animal model and restored levels of serum testosterone, steroidogenic enzymes, and spermatogenic cell apoptosis. These results demonstrate that ADSCs can contribute to testicular regeneration during aging. ADSCs also provide functional benefits through glycation suppression and antioxidant effects in a rat model of aging. Although some ADSCs differentiated into Leydig cells, the paracrine pathway seems to play a main role in this process, resulting in the reduction of apoptosis. © 2015 Wiley Periodicals, Inc.

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.

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

Science.gov (United States)

Lawless, Conor; Jurk, Diana; Gillespie, Colin S; Shanley, Daryl; Saretzki, Gabriele; von Zglinicki, Thomas; Passos, João F

2012-01-01

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.

Large, high-intensity fire events in Southern California shrublands: Debunking the fine-grain age patch model

Science.gov (United States)

Keeley, J.E.; Zedler, P.H.

2009-01-01

We evaluate the fine-grain age patch model of fire regimes in southern California shrublands. Proponents contend that the historical condition was characterized by frequent small to moderate size, slow-moving smoldering fires, and that this regime has been disrupted by fire suppression activities that have caused unnatural fuel accumulation and anomalously large and catastrophic wildfires. A review of more than 100 19th-century newspaper reports reveals that large, high-intensity wildfires predate modern fire suppression policy, and extensive newspaper coverage plus first-hand accounts support the conclusion that the 1889 Santiago Canyon Fire was the largest fire in California history. Proponents of the fine-grain age patch model contend that even the very earliest 20th-century fires were the result of fire suppression disrupting natural fuel structure. We tested that hypothesis and found that, within the fire perimeters of two of the largest early fire events in 1919 and 1932, prior fire suppression activities were insufficient to have altered the natural fuel structure. Over the last 130 years there has been no significant change in the incidence of large fires greater than 10000 ha, consistent with the conclusion that fire suppression activities are not the cause of these fire events. Eight megafires (???50 000 ha) are recorded for the region, and half have occurred in the last five years. These burned through a mosaic of age classes, which raises doubts that accumulation of old age classes explains these events. Extreme drought is a plausible explanation for this recent rash of such events, and it is hypothesized that these are due to droughts that led to increased dead fine fuels that promoted the incidence of firebrands and spot fires. A major shortcoming of the fine-grain age patch model is that it requires age-dependent flammability of shrubland fuels, but seral stage chaparral is dominated by short-lived species that create a dense surface layer of fine

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 base...... the independence assumption is rejected. Less fluctuating estimates of the fishing mortality is obtained due to a reduced process error. The improved model does not suffer from correlated residuals unlike the independent model, and the variance of forecasts is decreased....

Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly.

Science.gov (United States)

Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

2009-08-26

World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei) and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability. We propose that the implementation of the model active aging framework will permits the

Modeling the Phenotypic Architecture of Autism Symptoms from Time of Diagnosis to Age 6

Science.gov (United States)

Georgiades, Stelios; Boyle, Michael; Szatmari, Peter; Hanna, Steven; Duku, Eric; Zwaigenbaum, Lonnie; Bryson, Susan; Fombonne, Eric; Volden, Joanne; Mirenda, Pat; Smith, Isabel; Roberts, Wendy; Vaillancourt, Tracy; Waddell, Charlotte; Bennett, Teresa; Elsabbagh, Mayada; Thompson, Ann

2014-01-01

The latent class structure of autism symptoms from the time of diagnosis to age 6 years was examined in a sample of 280 children with autism spectrum disorder. Factor mixture modeling was performed on 26 algorithm items from the Autism Diagnostic Interview-Revised at diagnosis (Time 1) and again at age 6 (Time 2). At Time 1, a…

Modeling The Effects of Mother’s Age at First Birth on Child Health at Birth

OpenAIRE

Mbu Daniel Tambi

2014-01-01

This study models the impact of mother’s age at first birth on child health at birth in Cameroon. The objectives are: (1) investigate the implication of mother’s age at first birth on child health at birth; (2) examine the impact of mother’s age groups on birth weight, and (3) suggest economic policies to ameliorate the mother’s age – child health relationship. We make used of the control function approach to determine the relationship between mother’s age at first birth and birth...

Age, growth and population structure of invasive lionfish (Pterois volitans/miles in northeast Florida using a length-based, age-structured population model

Directory of Open Access Journals (Sweden)

Eric G. Johnson

2016-12-01

Full Text Available The effective management of invasive species requires detailed understanding of the invader’s life history. This information is essential for modeling population growth and predicting rates of expansion, quantifying ecological impacts and assessing the efficacy of removal and control strategies. Indo-Pacific lionfish (Pterois volitans/miles have rapidly invaded the western Atlantic, Gulf of Mexico and Caribbean Sea with documented negative impacts on native ecosystems. To better understand the life history of this species, we developed and validated a length-based, age-structured model to investigate age, growth and population structure in northeast Florida. The main findings of this study were: (1 lionfish exhibited rapid growth with seasonal variation in growth rates; (2 distinct cohorts were clearly identifiable in the length-frequency data, suggesting that lionfish are recruiting during a relatively short period in summer; and (3 the majority of lionfish were less than two years old with no lionfish older than three years of age, which may be the result of culling efforts as well as ontogenetic habitat shifts to deeper water.

Age, growth and population structure of invasive lionfish (Pterois volitans/miles) in northeast Florida using a length-based, age-structured population model.

Science.gov (United States)

Johnson, Eric G; Swenarton, Mary Katherine

2016-01-01

The effective management of invasive species requires detailed understanding of the invader's life history. This information is essential for modeling population growth and predicting rates of expansion, quantifying ecological impacts and assessing the efficacy of removal and control strategies. Indo-Pacific lionfish ( Pterois volitans/miles ) have rapidly invaded the western Atlantic, Gulf of Mexico and Caribbean Sea with documented negative impacts on native ecosystems. To better understand the life history of this species, we developed and validated a length-based, age-structured model to investigate age, growth and population structure in northeast Florida. The main findings of this study were: (1) lionfish exhibited rapid growth with seasonal variation in growth rates; (2) distinct cohorts were clearly identifiable in the length-frequency data, suggesting that lionfish are recruiting during a relatively short period in summer; and (3) the majority of lionfish were less than two years old with no lionfish older than three years of age, which may be the result of culling efforts as well as ontogenetic habitat shifts to deeper water.

Analysis of a general age-dependent vaccination model for a vertically transmitted disease

International Nuclear Information System (INIS)

El Doma, M.

1995-05-01

A SIR epidemic model of a general age-dependent vaccination for a vertically as well as horizontally transmitted disease is investigated when the total population is time dependent, and fertility, mortality and removal rates depend on age. We establish the existence and the uniqueness of the solution and obtain the asymptotic behaviour for the solution. For the steady state solution a critical vaccination coverage which will eventually eradicate the disease is determined. (author). 18 refs

Cellular models and therapies for age-related macular degeneration

Directory of Open Access Journals (Sweden)

David L. Forest

2015-05-01

Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

A Diffusion Model Analysis of Adult Age Differences in Episodic and Semantic Long-Term Memory Retrieval

Science.gov (United States)

Spaniol, Julia; Madden, David J.; Voss, Andreas

2006-01-01

Two experiments investigated adult age differences in episodic and semantic long-term memory tasks, as a test of the hypothesis of specific age-related decline in context memory. Older adults were slower and exhibited lower episodic accuracy than younger adults. Fits of the diffusion model (R. Ratcliff, 1978) revealed age-related increases in…

A structural model of age, grey matter volumes, education, and personality traits.

Science.gov (United States)

Kitamura, Soichiro; Yasuno, Fumihiko; Yamamoto, Akihide; Kazui, Hiroaki; Kudo, Takashi; Matsuoka, Kiwamu; Kiuchi, Kuniaki; Kosaka, Jun; Nagatsuka, Kazuyuki; Iida, Hidehiro; Kishimoto, Toshifumi

2016-01-01

When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education. We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors. The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score. Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

Science.gov (United States)

An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

2016-09-01

Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

Sensory Perception and Aging in Model Systems: From the Outside In

Science.gov (United States)

Linford, Nancy J.; Kuo, Tsung-Han; Chan, Tammy P.; Pletcher, Scott D.

2014-01-01

Sensory systems provide organisms from bacteria to human with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organism lifespan, have opened the door for powerful new research into aging. While direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging. PMID:21756108

A multiscale and multiphysics numerical framework for modelling of hygrothermal ageing in laminated composites

NARCIS (Netherlands)

Barcelos Carneiro M Rocha, Iuri; van der Meer, F.P.; Nijssen, RPL; Sluijs, Bert

2017-01-01

In this work, a numerical framework for modelling of hygrothermal ageing in laminated composites is proposed. The model consists of a macroscopic diffusion analysis based on Fick's second law coupled with a multiscale FE² stress analysis in order to take microscopic degradation

Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

Science.gov (United States)

Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

2018-06-14

Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at

Victimization, Suicidal Ideation, and Alcohol Use From Age 13 to 15 Years: Support for the Self-Medication Model.

Science.gov (United States)

Marschall-Lévesque, Shawn; Castellanos-Ryan, Natalie; Parent, Sophie; Renaud, Johanne; Vitaro, Frank; Boivin, Michel; Tremblay, Richard E; Séguin, Jean R

2017-04-01

Recent years have seen increased coverage of adolescent victimization and suicide. Both adolescent peer victimization and substance use have been associated with suicidal ideation, with evidence suggesting that all three factors are interrelated. There are at least four models which can explain the associations between these factors (i.e., self-medication, secondary mental disorder, bidirectional, and common factor). However, none of them is being empirically supported as the dominant model because few longitudinal studies have explored the association between these factors. The present study compared longitudinal paths of all four models simultaneously using a cross-lagged model. This was done using self-reported measures of peer victimization, suicidal ideation, and alcohol use at age 13, 14, and 15 years in a longitudinal sample of 238 adolescents. All three variables were moderately stable across time. Significant cross-lagged associations were found, showing that frequent peer victimization at age 13 years was associated with higher odds of having suicidal ideation at age 14 years (odds ratio, 1.82; p suicidal ideation at age 14 years was significantly associated with higher alcohol use frequency at age 15 years (β = .13; p suicidal ideation and alcohol use over 1 year, supporting the self-medication model. Clarifying the empirical basis of these underlying models could allow for earlier prevention strategies, by targeting the risk factor that appears the earliest in the model. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Protective effect of metformin on D-galactose-induced aging model in mice.

Science.gov (United States)

Fatemi, Iman; Khaluoi, Amin; Kaeidi, Ayat; Shamsizadeh, Ali; Heydari, Sara; Allahtavakoli, Mohammad Aa

2018-01-01

Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.

Developing a Maturity Model for Knowledge Management (KM) in the Digital Age

OpenAIRE

Thornley, Clare; Carcary, Marian; Connolly, Niall; O'Duffy, Michael; Pierce, John

2016-01-01

This paper arises from a work-in-progress academia/industry collaborative research project to develop a knowledge management (KM) maturity model as a component (critical capability) of the IT Capability Maturity Framework (IT-CMF). The aim of the project is to develop a knowledge management (KM) maturity model that is ‘fit for purpose’ for organisations in the digital age. In undertaking this work it became clear that, outside of the fundamental challenges of KM, new significant challenges an...

Delineating the third age: joint models of older people's quality of life and attrition in Britain 2002-2010.

Science.gov (United States)

Tampubolon, Gindo

2015-07-01

In the public mind, later life is being transformed by the emerging possibility of a flourishing third age with sustained quality of life. We draw trajectories of life quality measured using CASP-19 over eight years. We refine these trajectories by jointly modelling attrition, since older people tend to leave longitudinal studies (attrite) not at random. Growth curve models are applied to the English Longitudinal Study of Ageing waves 1 to 5. Then joint model is estimated where attrition is considered. Extensive predictors are entered including demographic attributes, social and economic status, health conditions, and behaviours. Strong non-linear age trajectory of life quality is revealed by the growth curve models where the peak is achieved in the late 60s. Then the joint model uncovers the peak somewhat later in time, and also reveals secular improvement in life quality experienced by recent cohorts. Sharp estimates for many predictors of higher levels of life quality are also found. For the first time, the trajectories of life quality in the third age are drawn and improvement across cohorts is demonstrated. The contributions are estimated for predictors amenable to intervention such as social capital. This can help in policy discussion on improving the lives of older people in the third age.

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

Directory of Open Access Journals (Sweden)

Se Eun Park

Full Text Available Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

Science.gov (United States)

Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

2016-01-01

Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

Probabilistic graphical models to deal with age estimation of living persons.

Science.gov (United States)

Sironi, Emanuele; Gallidabino, Matteo; Weyermann, Céline; Taroni, Franco

2016-03-01

Due to the rise of criminal, civil and administrative judicial situations involving people lacking valid identity documents, age estimation of living persons has become an important operational procedure for numerous forensic and medicolegal services worldwide. The chronological age of a given person is generally estimated from the observed degree of maturity of some selected physical attributes by means of statistical methods. However, their application in the forensic framework suffers from some conceptual and practical drawbacks, as recently claimed in the specialised literature. The aim of this paper is therefore to offer an alternative solution for overcoming these limits, by reiterating the utility of a probabilistic Bayesian approach for age estimation. This approach allows one to deal in a transparent way with the uncertainty surrounding the age estimation process and to produce all the relevant information in the form of posterior probability distribution about the chronological age of the person under investigation. Furthermore, this probability distribution can also be used for evaluating in a coherent way the possibility that the examined individual is younger or older than a given legal age threshold having a particular legal interest. The main novelty introduced by this work is the development of a probabilistic graphical model, i.e. a Bayesian network, for dealing with the problem at hand. The use of this kind of probabilistic tool can significantly facilitate the application of the proposed methodology: examples are presented based on data related to the ossification status of the medial clavicular epiphysis. The reliability and the advantages of this probabilistic tool are presented and discussed.

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)

Reliability of some ageing nuclear power plant systems: a simple stochastic model

International Nuclear Information System (INIS)

Suarez Antola, R.

2007-01-01

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 abovementioned 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

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

Directory of Open Access Journals (Sweden)

Correa-Muñoz Elsa

2009-08-01

Full Text Available Abstract Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i therapeutic adherence; (ii the incidence of the main chronic diseases in old age; (iii life expectancy without chronic diseases at 60 years of age; (iv disability adjusted life years lost; (v years of life lost due to premature mortality, and (vi years lived with disability. Discussion We propose that the

The bystander effect model of Brenner and Sachs fitted to lung cancer data in 11 cohorts of underground miners, and equivalence of fit of a linear relative risk model with adjustment for attained age and age at exposure

International Nuclear Information System (INIS)

Little, M P

2004-01-01

Bystander effects following exposure to α-particles have been observed in many experimental systems, and imply that linearly extrapolating low dose risks from high dose data might materially underestimate risk. Brenner and Sachs (2002 Int. J. Radiat. Biol. 78 593-604; 2003 Health Phys. 85 103-8) have recently proposed a model of the bystander effect which they use to explain the inverse dose rate effect observed for lung cancer in underground miners exposed to radon daughters. In this paper we fit the model of the bystander effect proposed by Brenner and Sachs to 11 cohorts of underground miners, taking account of the covariance structure of the data and the period of latency between the development of the first pre-malignant cell and clinically overt cancer. We also fitted a simple linear relative risk model, with adjustment for age at exposure and attained age. The methods that we use for fitting both models are different from those used by Brenner and Sachs, in particular taking account of the covariance structure, which they did not, and omitting certain unjustifiable adjustments to the miner data. The fit of the original model of Brenner and Sachs (with 0 y period of latency) is generally poor, although it is much improved by assuming a 5 or 6 y period of latency from the first appearance of a pre-malignant cell to cancer. The fit of this latter model is equivalent to that of a linear relative risk model with adjustment for age at exposure and attained age. In particular, both models are capable of describing the observed inverse dose rate effect in this data set

The importance of age dependent mortality and the extrinsic incubation period in models of mosquito-borne disease transmission and control.

Directory of Open Access Journals (Sweden)

Steve E Bellan

2010-04-01

Full Text Available Nearly all mathematical models of vector-borne diseases have assumed that vectors die at constant rates. However, recent empirical research suggests that mosquito mortality rates are frequently age dependent. This work develops a simple mathematical model to assess how relaxing the classical assumption of constant mortality affects the predicted effectiveness of anti-vectorial interventions. The effectiveness of mosquito control when mosquitoes die at age dependent rates was also compared across different extrinsic incubation periods. Compared to a more realistic age dependent model, constant mortality models overestimated the sensitivity of disease transmission to interventions that reduce mosquito survival. Interventions that reduce mosquito survival were also found to be slightly less effective when implemented in systems with shorter EIPs. Future transmission models that examine anti-vectorial interventions should incorporate realistic age dependent mortality rates.

Comparison of Different Height–Diameter Modelling Techniques for Prediction of Site Productivity in Natural Uneven-Aged Pure Stands

Directory of Open Access Journals (Sweden)

Guangshuang Duan

2018-01-01

Full Text Available Reliable estimates of forest site productivity are a central element of forest management. The model of height-diameter relationship of dominant trees using algebraic difference approach (ADA is a commonly used method to measure site productivity of natural uneven-aged stands. However, the existing models of this method do not recognize site type or sample plot specific variability in height curves; thus, it cannot be effectively used to estimate site type or sample plot-related site productivity for natural uneven-aged stands. Two primary subject-specific approaches, ADA with dummy variable (DV (ADA + DV and ADA with combination of dummy variable and nonlinear mixed-effects modelling (CM (ADA + CM, were proposed for height–diameter modelling. Height–diameter models developed with ADA, ADA + DV and ADA + CM were compared using data from 4161 observations on 349 permanent sample plots of four major natural uneven-aged pure stands (Spruce, Korean Larch, Mongolian Oak, and White Birch in northeastern China. It was found that models developed with ADA + CM provided the best performance, followed by the models with ADA + DV, and the models developed with ADA performed the worst. Random effects at the plot level were substantial, and their inclusion greatly improved the model’s accuracy. More importantly, the models developed with ADA + CM provide an effective method for quantifying site type- and sample plot-specific forest site productivity for uneven-aged pure stands.

Stochastic model for the 3D microstructure of pristine and cyclically aged cathodes in Li-ion batteries

Science.gov (United States)

Kuchler, Klaus; Westhoff, Daniel; Feinauer, Julian; Mitsch, Tim; Manke, Ingo; Schmidt, Volker

2018-04-01

It is well-known that the microstructure of electrodes in lithium-ion batteries strongly affects their performance. Vice versa, the microstructure can exhibit strong changes during the usage of the battery due to aging effects. For a better understanding of these effects, mathematical analysis and modeling has turned out to be of great help. In particular, stochastic 3D microstructure models have proven to be a powerful and very flexible tool to generate various kinds of particle-based structures. Recently, such models have been proposed for the microstructure of anodes in lithium-ion energy and power cells. In the present paper, we describe a stochastic modeling approach for the 3D microstructure of cathodes in a lithium-ion energy cell, which differs significantly from the one observed in anodes. The model for the cathode data enhances the ideas of the anode models, which have been developed so far. It is calibrated using 3D tomographic image data from pristine as well as two aged cathodes. A validation based on morphological image characteristics shows that the model is able to realistically describe both, the microstructure of pristine and aged cathodes. Thus, we conclude that the model is suitable to generate virtual, but realistic microstructures of lithium-ion cathodes.

Some considerations in applying stock-recruitment models to multiple-age spawning populations

International Nuclear Information System (INIS)

Lawler, P.J.

1988-01-01

Several approaches used during the Hudson River power plant hearings (1977-1980) to permit quantitative estimation of the impact of power plant operation on the river's striped bass population are presented. The Ricker stock-recruitment model was adopted as a starting point to provide a reasonable working conceptualization of the stock-recruitment processes operating in this river. This model was then modified in a variety of ways to reflect multiple-age spawning by striped bass, and the results were fit to data on the river's commercial striped bass catch and effort, organized to reflect certain average age distribution parameters. Environmental variation in the system, represented in an overall fashion by the spring and summer variation in the river's freshwater flow, and the effect of certain assumed modes of cannibalism were also included in these analyses. Quantitative estimates of the Ricker parameters alpha and beta representing compensatory reserve and density dependent mortality, respectively, in the system were extracted from these fits. In addition, an approach to modeling the influence of certain density-dependent and density-independent growth factors on the various modes of mortality is presented. All of the above procedures are directed toward estimating the change a given impact may induce on the stock-recruitment model parameters alpha and beta. These changes in alpha and beta are used in various equilibrium reduction models to estimate the percentage change in the equilibrium spawning population that, all other things remaining equal, can be expected in the presence of the impact under study. 15 refs., 3 tabs

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.

Testing the effects of topography, geometry, and kinematics on modeled thermochronometer cooling ages in the eastern Bhutan Himalaya

Science.gov (United States)

Gilmore, Michelle E.; McQuarrie, Nadine; Eizenhöfer, Paul R.; Ehlers, Todd A.

2018-05-01

In this study, reconstructions of a balanced geologic cross section in the Himalayan fold-thrust belt of eastern Bhutan are used in flexural-kinematic and thermokinematic models to understand the sensitivity of predicted cooling ages to changes in fault kinematics, geometry, topography, and radiogenic heat production. The kinematics for each scenario are created by sequentially deforming the cross section with ˜ 10 km deformation steps while applying flexural loading and erosional unloading at each step to develop a high-resolution evolution of deformation, erosion, and burial over time. By assigning ages to each increment of displacement, we create a suite of modeled scenarios that are input into a 2-D thermokinematic model to predict cooling ages. Comparison of model-predicted cooling ages to published thermochronometer data reveals that cooling ages are most sensitive to (1) the location and size of fault ramps, (2) the variable shortening rates between 68 and 6.4 mm yr-1, and (3) the timing and magnitude of out-of-sequence faulting. The predicted ages are less sensitive to (4) radiogenic heat production and (5) estimates of topographic evolution. We used the observed misfit of predicted to measured cooling ages to revise the cross section geometry and separate one large ramp previously proposed for the modern décollement into two smaller ramps. The revised geometry results in an improved fit to observed ages, particularly young AFT ages (2-6 Ma) located north of the Main Central Thrust. This study presents a successful approach for using thermochronometer data to test the viability of a proposed cross section geometry and kinematics and describes a viable approach to estimating the first-order topographic evolution of a compressional orogen.

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…

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…

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

NARCIS (Netherlands)

de Ree, Joppe; Alessie, Rob

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

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit hydroalcoholic extract in D-galactose-induced aging mouse model.

Science.gov (United States)

Ahangarpour, Akram; Oroojan, Ali Akbar; Khorsandi, Layasadat; Najimi, Seyedeh Asma

2017-04-01

D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30-35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC hydroalcoholic extract. The aged model was prepared by subcutaneous injection of D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day in the last 7 days. 24 h after the last drug and extract administrations, serum samples and pancreatic tissues were removed to evaluate experimental and histological determinations. Serum glucose level decreased in VAC, D-galactose and, aged-treated groups compared to the control ( P < 0.05). Insulin level increased in VAC and decreased in D-galactose and aged VAC-treated mice compared to the control ( P < 0.05). Homeostasis model assessment-estimated insulin resistance (HOMA-IR) increased in D-galactose, aging, and VAC hydroalcoholic extract groups ( P < 0.05) and, administration of VAC hydroalcoholic extract improved HOMA-IR in D-galactose and aging treated animals. Despite the size of pancreatic islets decreased in aged and D-galactose groups, VAC administration recovered it. Present data showed that VAC hydroalcoholic extract has hypoglycemic and pancreatic protective effects in natural aged and aging model mice.

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.

A method of computer modelling the lithium-ion batteries aging process based on the experimental characteristics

Science.gov (United States)

Czerepicki, A.; Koniak, M.

2017-06-01

The paper presents a method of modelling the processes of aging lithium-ion batteries, its implementation as a computer application and results for battery state estimation. Authors use previously developed behavioural battery model, which was built using battery operating characteristics obtained from the experiment. This model was implemented in the form of a computer program using a database to store battery characteristics. Batteries aging process is a new extended functionality of the model. Algorithm of computer simulation uses a real measurements of battery capacity as a function of the battery charge and discharge cycles number. Simulation allows to take into account the incomplete cycles of charge or discharge battery, which are characteristic for transport powered by electricity. The developed model was used to simulate the battery state estimation for different load profiles, obtained by measuring the movement of the selected means of transport.

Brain age and other bodily 'ages': implications for neuropsychiatry.

Science.gov (United States)

Cole, James H; Marioni, Riccardo E; Harris, Sarah E; Deary, Ian J

2018-06-11

As our brains age, we tend to experience cognitive decline and are at greater risk of neurodegenerative disease and dementia. Symptoms of chronic neuropsychiatric diseases are also exacerbated during ageing. However, the ageing process does not affect people uniformly; nor, in fact, does the ageing process appear to be uniform even within an individual. Here, we outline recent neuroimaging research into brain ageing and the use of other bodily ageing biomarkers, including telomere length, the epigenetic clock, and grip strength. Some of these techniques, using statistical approaches, have the ability to predict chronological age in healthy people. Moreover, they are now being applied to neurological and psychiatric disease groups to provide insights into how these diseases interact with the ageing process and to deliver individualised predictions about future brain and body health. We discuss the importance of integrating different types of biological measurements, from both the brain and the rest of the body, to build more comprehensive models of the biological ageing process. Finally, we propose seven steps for the field of brain-ageing research to take in coming years. This will help us reach the long-term goal of developing clinically applicable statistical models of biological processes to measure, track and predict brain and body health in ageing and disease.

Constructing Regional Groundwater Models from Geophysical Data of Varying Type, Age, and Quality

DEFF Research Database (Denmark)

Vest Christiansen, Anders; Auken, Esben; Marker, Pernille Aabye

for parameterization of a 3D model of the subsurface, integrating lithological information from boreholes with resistivity models. The objective is to create a direct input to regional groundwater models for sedimentary areas, where the sand/clay distribution governs the groundwater flow. The resistivity input is all......-inclusive in the sense that we include data from a variety of instruments (DC and EM, ground-based and airborne), with a varying spatial density and varying ages and quality. The coupling between hydrological and geophysical parameters is managed using a translator function with spatially variable parameters, which...

Modeling basic creep in concrete at early-age under compressive and tensile loading

Energy Technology Data Exchange (ETDEWEB)

Hilaire, Adrien, E-mail: adrien.hilaire@ens-cachan.fr [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France); Benboudjema, Farid; Darquennes, Aveline; Berthaud, Yves [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France); Nahas, Georges [ENS Cachan/CNRS UMR8535/UPMC/PRES UniverSud Paris, Cachan (France); Institut de radioprotection et de sureté nucléaire, Fontenay-aux-Roses (France)

2014-04-01

A numerical model has been developed to predict early age cracking for massive concrete structures, and especially concrete nuclear containment vessels. Major phenomena are included: hydration, heat diffusion, autogenous and thermal shrinkage, creep and cracking. Since studied structures are massive, drying is not taken into account. Such modeling requires the identification of several material parameters. Literature data is used to validate the basic creep model. A massive wall, representative of a concrete nuclear containment, is simulated; predicted cracking is consistent with observation and is found highly sensitive to the creep phenomenon.

Degradations analysis and aging modeling for health assessment and prognostics of PEMFC

International Nuclear Information System (INIS)

Jouin, Marine; Gouriveau, Rafael; Hissel, Daniel; Péra, Marie-Cécile; Zerhouni, Noureddine

2016-01-01

Applying prognostics to Proton Exchange Membrane Fuel Cell (PEMFC) stacks is a good solution to help taking actions extending their lifetime. However, it requires a great understanding of the degradation mechanisms and failures occurring within the stack. This task is not simple when applied to a PEMFC due to the different levels (stack - cells - components), the different scales and the multiple causes that lead to degradation. To overcome this problem, this work proposes a methodology dedicated to the setting of a framework and a modeling of the aging for prognostics. This methodology is based on a deep literature review and degradation analyses of PEMFC stacks. This analysis allows defining a proper vocabulary dedicated to PEMFC's prognostics and health management and a clear limited framework to perform prognostics. Then the degradations review is used to select critical components within the stack, and to define their critical failure mechanisms thanks the proposal of new fault trees. The impact of these critical components and mechanisms on the power loss during aging is included to the model for prognostics. This model is finally validated on four datasets with different mission profiles both for health assessment and prognostics. - Highlights: • A proper framework to perform PHM, particularly prognostics, of PEMFC is proposed. • A degradation analysis is performed. • A completely new model of PEMFC degradation is proposed. • SOH estimation is performed with very high coefficients of determination.

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…

Probabilistic risk analysis of aging components which fail on demand. A Bayesian model. Application to maintenance optimization of Diesel engine linings

International Nuclear Information System (INIS)

Procaccia, H.; Lannoy, A.; Clarotti, C.A.

1997-01-01

The optimization of preventive maintenance of aging materials can be well modelled through the application of the two-parameters Weibull law. Unfortunately there is no theoretical model describing the aging of components implied in emergency interventions which may fail in very moment of demand. These components are relevant to the safety of Nuclear Power Plants and the main problem with them is the optimization of the maintenance and the test schedule. Indeed the effect of any test is twofold, namely: the test reveals failures which otherwise would occur when the Power Plant would need urgent intervention but at the same time it causes the aging process to step up. The aging process is suspected to affect certain safeguard equipment, but it does not exist a theoretical model of component aging in function of demands. Sections 2.1 and 2.2 of the paper are devoted to the description of a Bayesian model of discrete aging, deriving the likelihood function of the model (data modelling) and to selecting 'the best prior' (Analyst knowledge) that can be associated to the likelihood, respectively. The aspects of numerical integration relative to assessing the predictive reliability of the aging components are discussed in Section 2.3. Section 3 reports a Reliability Centered Maintenance application of the model to cylinders of emergency electrical generators of the NPP nuclear sectors. These components are subjected to an annual endoscopic checking and to a systematical replacement at every 5 years. The statistical Bayesian decision theory was applied to determine an optimal period of cylinder replacement based on the aging model presented in this paper. It is shown that the optimal value is between 10 to 12 years. (author)

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......, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allows...

A partial exponential lumped parameter model to evaluate groundwater age distributions and nitrate trends in long-screened wells

Science.gov (United States)

Jurgens, Bryant; Böhlke, 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.

Batteries 2020 – Lithium - ion battery first and second life ageing, validated battery models, lifetime modelling and ageing assessment of thermal parameters

DEFF Research Database (Denmark)

Timmermans, Jean-Marc; Nikolian, Alexandros; De Hoog, Joris

2016-01-01

The European Project “Batteries 2020” unites nine partners jointly working on research and the development of competitive European automotive batteries. The project aims at increasing both the energy density and lifetime of large format pouch lithium-ion batteries towards the goals targeted...... vehicle application. These batteries are still operational and suitable to less restrictive conditions, such as those for stationary and renewable energy application. Therefore, possible second life opportunities have been identified and further assessed. In this paper, the main ageing effects of lithium...... ion batteries are explained. Next, an overview of different validated battery models will be discussed. Finally, a methodology for assessing the performance of the battery cells in a second life application is presented....

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

-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......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...... 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....

Understanding trends in Australian alcohol consumption-an age-period-cohort model.

Science.gov (United States)

Livingston, Michael; Raninen, Jonas; Slade, Tim; Swift, Wendy; Lloyd, Belinda; Dietze, Paul

2016-09-01

To decompose Australian trends in alcohol consumption into their age, period (survey year) and cohort (birth year/generation) components. In particular, we aimed to test whether recent declines in overall consumption have been influenced by reductions in drinking among recently born cohorts. Seven cross-sectional waves of the Australian National Drug Strategy Household Survey (1995-2013). Age, period and cohort effects were estimated using a linear and logistic cross-classified random-effects models (CCREMs). Australia A total of 124 440 Australians (69 193 females and 55 257 males), aged 14-79 years. Whether or not respondents consumed alcohol in the 12 months prior to the survey and, for those who did, the estimated volume of pure alcohol consumed, derived using standard quantity-frequency survey questions. Controlling for age and period effects, there was significant variation in drinking participation and drinking volume by birth cohort. In particular, male cohorts born between the 1965 and 1974 and female cohorts born between 1955 and 1974 reported higher rates of drinking participation (P women (P < 0.01). Recent birth cohorts (born between 1995 and 1999) in Australia report significantly lower rates of both drinking participation and drinking volume than previous cohorts, controlling for their age distribution and overall changes in population drinking. These findings suggest that the recent decline in alcohol consumption in Australia has been driven by declines in drinking among these recently born cohorts. These trends are consistent with international shifts in youth drinking. © 2016 Society for the Study of Addiction.

Modelling the genesis of equatorial podzols: age and implications for carbon fluxes

Science.gov (United States)

Doupoux, Cédric; Merdy, Patricia; Régina Montes, Célia; Nunan, Naoise; José Melfi, Adolpho; José Ribeiro Pereira, Osvaldo; Lucas, Yves

2017-05-01

Amazonian podzols store huge amounts of carbon and play a key role in transferring organic matter to the Amazon River. In order to better understand their C dynamics, we modelled the formation of representative Amazonian podzol profiles by constraining both total carbon and radiocarbon. We determined the relationships between total carbon and radiocarbon in organic C pools numerically by setting constant C and 14C inputs over time. The model was an effective tool for determining the order of magnitude of the carbon fluxes and the time of genesis of the main carbon-containing horizons, i.e. the topsoil and deep Bh. We performed retrocalculations to take into account the bomb carbon in the young topsoil horizons (calculated apparent 14C age from 62 to 109 years). We modelled four profiles representative of Amazonian podzols, two profiles with an old Bh (calculated apparent 14C age 6.8 × 103 and 8.4 × 103 years) and two profiles with a very old Bh (calculated apparent 14C age 23.2 × 103 and 25.1 × 103 years). The calculated fluxes from the topsoil to the perched water table indicate that the most waterlogged zones of the podzolized areas are the main source of dissolved organic matter found in the river network. It was necessary to consider two Bh carbon pools to accurately represent the carbon fluxes leaving the Bh as observed in previous studies. We found that the genesis time of the studied soils was necessarily longer than 15 × 103 and 130 × 103 years for the two younger and two older Bhs, respectively, and that the genesis time calculated considering the more likely settings runs to around 15 × 103-25 × 103 and 150 × 103-250 × 103 years, respectively.

How does aging affect recognition-based inference? A hierarchical Bayesian modeling approach.

Science.gov (United States)

Horn, Sebastian S; Pachur, Thorsten; Mata, Rui

2015-01-01

The recognition heuristic (RH) is a simple strategy for probabilistic inference according to which recognized objects are judged to score higher on a criterion than unrecognized objects. In this article, a hierarchical Bayesian extension of the multinomial r-model is applied to measure use of the RH on the individual participant level and to re-evaluate differences between younger and older adults' strategy reliance across environments. Further, it is explored how individual r-model parameters relate to alternative measures of the use of recognition and other knowledge, such as adherence rates and indices from signal-detection theory (SDT). Both younger and older adults used the RH substantially more often in an environment with high than low recognition validity, reflecting adaptivity in strategy use across environments. In extension of previous analyses (based on adherence rates), hierarchical modeling revealed that in an environment with low recognition validity, (a) older adults had a stronger tendency than younger adults to rely on the RH and (b) variability in RH use between individuals was larger than in an environment with high recognition validity; variability did not differ between age groups. Further, the r-model parameters correlated moderately with an SDT measure expressing how well people can discriminate cases where the RH leads to a correct vs. incorrect inference; this suggests that the r-model and the SDT measures may offer complementary insights into the use of recognition in decision making. In conclusion, younger and older adults are largely adaptive in their application of the RH, but cognitive aging may be associated with an increased tendency to rely on this strategy. Copyright © 2014 Elsevier B.V. All rights reserved.

Aging aggravates long-term renal ischemia-reperfusion injury in a rat model.

Science.gov (United States)

Xu, Xianlin; Fan, Min; He, Xiaozhou; Liu, Jipu; Qin, Jiandi; Ye, Jianan

2014-03-01

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI. Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed. Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI. Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

Science.gov (United States)

Schneider, Uwe; Walsh, Linda

2015-08-01

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for

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

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.

Science.gov (United States)

Lim, Patrick H; Wert, Stephanie L; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana; Redei, Eva E

2018-02-25

Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. Copyright © 2018 Elsevier B.V. All rights reserved.