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Sample records for ageing model podospora

  1. Identification of autophagy as a longevity-assurance mechanism in the aging model Podospora anserina

    PubMed Central

    Knuppertz, Laura; Hamann, Andrea; Pampaloni, Francesco; Stelzer, Ernst; Osiewacz, Heinz D

    2014-01-01

    The filamentous ascomycete Podospora anserina is a well-established aging model in which a variety of different pathways, including those involved in the control of respiration, ROS generation and scavenging, DNA maintenance, proteostasis, mitochondrial dynamics, and programmed cell death have previously been demonstrated to affect aging and life span. Here we address a potential role of autophagy. We provide data demonstrating high basal autophagy levels even in strains cultivated under noninduced conditions. By monitoring an N-terminal fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus on medium with and without nitrogen supplementation, respectively, we identified a significant increase of GFP puncta in older and in nitrogen-starved cultures suggesting an induction of autophagy during aging. This conclusion is supported by the demonstration of an age-related and autophagy-dependent degradation of a PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of the PaATG1 serine/threonine kinase active in early stages of autophagy induction, impairs ascospore germination and development and shortens life span. Under nitrogen-depleted conditions, life span of the wild type is increased almost 4-fold. In contrast, this effect is annihilated in the Paatg1 deletion strain, suggesting that the ability to induce autophagy is beneficial for this fungus. Collectively, our data identify autophagy as a longevity-assurance mechanism in P. anserina and as another surveillance pathway in the complex network of pathways affecting aging and development. These findings provide perspectives for the elucidation of the mechanisms involved in the regulation of individual pathways and their interactions. PMID:24584154

  2. Genetic control of anastomosis in Podospora anserina.

    PubMed

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

    2014-09-01

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

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

    PubMed

    Grimm, Carolin; Osiewacz, Heinz D

    2015-03-01

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

  4. Peroxisome dynamics during development of the fungus Podospora anserina.

    PubMed

    Takano-Rojas, Harumi; Zickler, Denise; Peraza-Reyes, Leonardo

    2016-01-01

    Peroxisomes are versatile and dynamic organelles that are required for the development of diverse eukaryotic organisms. We demonstrated previously that in the fungus Podospora anserina different peroxisomal functions are required at distinct stages of sexual development, including the initiation and progression of meiocyte (ascus) development and the differentiation and germination of sexual spores (ascospores). Peroxisome assembly during these processes relies on the differential activity of the protein machinery that drives the import of proteins into the organelle, indicating a complex developmental regulation of peroxisome formation and activity. Here we demonstrate that peroxisome dynamics is also highly regulated during development. We show that peroxisomes in P. anserina are highly dynamic and respond to metabolic and environmental cues by undergoing changes in size, morphology and number. In addition, peroxisomes of vegetative and sexual cell types are structurally different. During sexual development peroxisome number increases at two stages: at early ascus differentiation and during ascospore formation. These processes are accompanied by changes in peroxisome structure and distribution, which include a cell-polarized concentration of peroxisomes at the beginning of ascus development, as well as a morphological transition from predominantly spherical to elongated shapes at the end of the first meiotic division. Further, the mostly tubular peroxisomes present from second meiotic division to early ascospore formation again become rounded during ascospore differentiation. Ultimately the number of peroxisomes dramatically decreases upon ascospore maturation. Our results reveal a precise regulation of peroxisome dynamics during sexual development and suggest that peroxisome constitution and function during development is defined by the coordinated regulation of the proteins that control peroxisome assembly and dynamics.

  5. Insights into Exo- and Endoglucanase Activities of Family 6 Glycoside Hydrolases from Podospora anserina

    PubMed Central

    Poidevin, Laetitia; Feliu, Julia; Doan, Annick; Berrin, Jean-Guy; Bey, Mathieu; Coutinho, Pedro M.; Henrissat, Bernard; Record, Eric

    2013-01-01

    The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings of herbivores. Its genome encodes a large diversity of carbohydrate-active enzymes. Among them, four genes encode glycoside hydrolases from family 6 (GH6), the members of which comprise putative endoglucanases and exoglucanases, some of them exerting important functions for biomass degradation in fungi. Therefore, this family was selected for functional analysis. Three of the enzymes, P. anserina Cel6A (PaCel6A), PaCel6B, and PaCel6C, were functionally expressed in the yeast Pichia pastoris. All three GH6 enzymes hydrolyzed crystalline and amorphous cellulose but were inactive on hydroxyethyl cellulose, mannan, galactomannan, xyloglucan, arabinoxylan, arabinan, xylan, and pectin. PaCel6A had a catalytic efficiency on cellotetraose comparable to that of Trichoderma reesei Cel6A (TrCel6A), but PaCel6B and PaCel6C were clearly less efficient. PaCel6A was the enzyme with the highest stability at 45°C, while PaCel6C was the least stable enzyme, losing more than 50% of its activity after incubation at temperatures above 30°C for 24 h. In contrast to TrCel6A, all three studied P. anserina GH6 cellulases were stable over a wide range of pHs and conserved high activity at pH values of up to 9. Each enzyme displayed a distinct substrate and product profile, highlighting different modes of action, with PaCel6A being the enzyme most similar to TrCel6A. PaCel6B was the only enzyme with higher specific activity on carboxymethylcellulose (CMC) than on Avicel and showed lower processivity than the others. Structural modeling predicts an open catalytic cleft, suggesting that PaCel6B is an endoglucanase. PMID:23645193

  6. Cytosolic Ribosomal Mutations That Abolish Accumulation of Circular Intron in the Mitochondria without Preventing Senescence of Podospora Anserina

    PubMed Central

    Silar, P.; Koll, F.; Rossignol, M.

    1997-01-01

    The filamentous fungus Podospora anserina presents a degeneration syndrome called Senescence associated with mitochondrial DNA modifications. We show that mutations affecting the two different and interacting cytosolic ribosomal proteins (S7 and S19) systematically and specifically prevent the accumulation of senDNAα (a circular double-stranded DNA plasmid derived from the first intron of the mitochondrial cox1 gene or intron α) without abolishing Senescence nor affecting the accumulation of other usually observed mitochondrial DNA rearrangements. One of the mutant proteins is homologous to the Escherichia coli S4 and Saccharomyces cerevisiae S13 ribosomal proteins, known to be involved in accuracy control of cytosolic translation. The lack of accumulation of senDNAα seems to result from a nontrivial ribosomal alteration unrelated to accuracy control, indicating that S7 and S19 proteins have an additional function. The results strongly suggest that modified expression of nucleus-encoded proteins contributes to Senescence in P. anserina. These data do not fit well with some current models, which propose that intron α plays the role of the cytoplasmic and infectious Determinant of Senescence that was defined in early studies. PMID:9055079

  7. Modeled ground water age distributions

    USGS Publications Warehouse

    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.

  8. Modeled ground water age distributions.

    PubMed

    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.

  9. ALL AGES LEAD MODEL

    EPA Science Inventory

    The Integrated Exposure Uptake Biokinetic (IEUBK) Model for Lead in Children (version 0.99d) was released in March 1994, and has been widely accepted in the risk assessment community as a tool for implementing the site specific risk assessment process when the issue is childhood...

  10. Aging Research Using Mouse Models.

    PubMed

    Ackert-Bicknell, Cheryl L; Anderson, Laura C; Sheehan, Susan; Hill, Warren G; Chang, Bo; Churchill, Gary A; Chesler, Elissa J; Korstanje, Ron; Peters, Luanne L

    2015-06-01

    Despite the dramatic increase in human lifespan over the past century, there remains pronounced variability in "health-span," or the period of time in which one is generally healthy and free of disease. Much of the variability in health-span and lifespan is thought to be genetic in origin. Understanding the genetic mechanisms of aging and identifying ways to boost longevity is a primary goal in aging research. Here, we describe a pipeline of phenotypic assays for assessing mouse models of aging. This pipeline includes behavior/cognition testing, body composition analysis, and tests of kidney function, hematopoiesis, and immune function, as well as physical parameters. We also describe study design methods for assessing lifespan and health-span, and other important considerations when conducting aging research in the laboratory mouse. The tools and assays provided can assist researchers with understanding the correlative relationships between age-associated phenotypes and, ultimately, the role of specific genes in the aging process.

  11. Aging Research Using Mouse Models

    PubMed Central

    Ackert-Bicknell, Cheryl L.; Anderson, Laura; Sheehan, Susan; Hill, Warren G.; Chang, Bo; Churchill, Gary A.; Chesler, Elissa J.; Korstanje, Ron; Peters, Luanne L.

    2015-01-01

    Despite the dramatic increase in human lifespan over the past century, there remains pronounced variability in “health-span”, or the period of time in which one is generally healthy and free of disease. Much of the variability in health-span and lifespan is thought to be genetic in origin. Understanding the genetic mechanisms of aging and identifying ways to boost longevity is a primary goal in aging research. Here, we describe a pipeline of phenotypic assays for assessing mouse models of aging. This pipeline includes behavior/cognition testing, body composition analysis, and tests of kidney function, hematopoiesis, immune function and physical parameters. We also describe study design methods for assessing lifespan and health-span, and other important considerations when conducting aging research in the laboratory mouse. The tools and assays provided can assist researchers with understanding the correlative relationships between age-associated phenotypes and, ultimately, the role of specific genes in the aging process. PMID:26069080

  12. Genome-Wide Gene Expression Profiling of Fertilization Competent Mycelium in Opposite Mating Types in the Heterothallic Fungus Podospora anserina

    PubMed Central

    Coppin, Evelyne; Imbeaud, Sandrine; Grognet, Pierre; Delacroix, Hervé; Debuchy, Robert

    2011-01-01

    Background Mating-type loci in yeasts and ascomycotan filamentous fungi (Pezizomycotina) encode master transcriptional factors that play a critical role in sexual development. Genome-wide analyses of mating-type-specification circuits and mating-type target genes are available in Saccharomyces cerevisiae and Schizosaccharomyces pombe; however, no such analyses have been performed in heterothallic (self-incompatible) Pezizomycotina. The heterothallic fungus Podospora anserina serves as a model for understanding the basic features of mating-type control. Its mat+ and mat− mating types are determined by dissimilar allelic sequences. The mat− sequence contains three genes, designated FMR1, SMR1 and SMR2, while the mat+ sequence contains one gene, FPR1. FMR1 and FPR1 are the major regulators of fertilization, and this study presents a genome-wide view of their target genes and analyzes their target gene regulation. Methodology/Principal Findings The transcriptomic profiles of the mat+ and mat− strains revealed 157 differentially transcribed genes, and transcriptomic analysis of fmr1− and fpr1− mutant strains was used to determine the regulatory actions exerted by FMR1 and FPR1 on these differentially transcribed genes. All possible combinations of transcription repression and/or activation by FMR1 and/or FPR1 were observed. Furthermore, 10 additional mating-type target genes were identified that were up- or down-regulated to the same level in mat+ and mat− strains. Of the 167 genes identified, 32 genes were selected for deletion, which resulted in the identification of two genes essential for the sexual cycle. Interspecies comparisons of mating-type target genes revealed significant numbers of orthologous pairs, although transcriptional profiles were not conserved between species. Conclusions/Significance This study represents the first comprehensive genome-wide analysis of mating-type direct and indirect target genes in a heterothallic filamentous fungus

  13. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research.

  14. A Network of HMG-box Transcription Factors Regulates Sexual Cycle in the Fungus Podospora anserina

    PubMed Central

    Ait Benkhali, Jinane; Coppin, Evelyne; Brun, Sylvain; Peraza-Reyes, Leonardo; Martin, Tom; Dixelius, Christina; Lazar, Noureddine; van Tilbeurgh, Herman; Debuchy, Robert

    2013-01-01

    High-mobility group (HMG) B proteins are eukaryotic DNA-binding proteins characterized by the HMG-box functional motif. These transcription factors play a pivotal role in global genomic functions and in the control of genes involved in specific developmental or metabolic pathways. The filamentous ascomycete Podospora anserina contains 12 HMG-box genes. Of these, four have been previously characterized; three are mating-type genes that control fertilization and development of the fruit-body, whereas the last one encodes a factor involved in mitochondrial DNA stability. Systematic deletion analysis of the eight remaining uncharacterized HMG-box genes indicated that none were essential for viability, but that seven were involved in the sexual cycle. Two HMG-box genes display striking features. PaHMG5, an ortholog of SpSte11 from Schizosaccharomyces pombe, is a pivotal activator of mating-type genes in P. anserina, whereas PaHMG9 is a repressor of several phenomena specific to the stationary phase, most notably hyphal anastomoses. Transcriptional analyses of HMG-box genes in HMG-box deletion strains indicated that PaHMG5 is at the hub of a network of several HMG-box factors that regulate mating-type genes and mating-type target genes. Genetic analyses revealed that this network also controls fertility genes that are not regulated by mating-type transcription factors. This study points to the critical role of HMG-box members in sexual reproduction in fungi, as 11 out of 12 members were involved in the sexual cycle in P. anserina. PaHMG5 and SpSte11 are conserved transcriptional regulators of mating-type genes, although P. anserina and S. pombe diverged 550 million years ago. Two HMG-box genes, SOX9 and its upstream regulator SRY, also play an important role in sex determination in mammals. The P. anserina and S. pombe mating-type genes and their upstream regulatory factor form a module of HMG-box genes analogous to the SRY/SOX9 module, revealing a commonality of sex

  15. Aging Successfully: A Four-Factor Model

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  16. Modelling the molecular mechanisms of aging.

    PubMed

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

    2017-02-28

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

  17. Modelling the molecular mechanisms of aging

    PubMed Central

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

    2017-01-01

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

  18. Estimating Neuronal Ageing with Hidden Markov Models

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Pham, Tuan D.

    2011-06-01

    Neuronal degeneration is widely observed in normal ageing, meanwhile the neurode-generative disease like Alzheimer's disease effects neuronal degeneration in a faster way which is considered as faster ageing. Early intervention of such disease could benefit subjects with potentials of positive clinical outcome, therefore, early detection of disease related brain structural alteration is required. In this paper, we propose a computational approach for modelling the MRI-based structure alteration with ageing using hidden Markov model. The proposed hidden Markov model based brain structural model encodes intracortical tissue/fluid distribution using discrete wavelet transformation and vector quantization. Further, it captures gray matter volume loss, which is capable of reflecting subtle intracortical changes with ageing. Experiments were carried out on healthy subjects to validate its accuracy and robustness. Results have shown its ability of predicting the brain age with prediction error of 1.98 years without training data, which shows better result than other age predition methods.

  19. [Deafness and aging: studies in experimental models].

    PubMed

    Gil Loyzaga, Pablo E

    2002-01-01

    Since 1970 a progressive aging of the world population, mainly in the most developed countries, has been observed. Spain could have, around 2050, the most aged human population of the world. Therefore, scientist show an increasing interest on the study of the aging-related pathologies (i.e. deafness linked to aging process: presbycusis). The deep analysis of the presbycusis physiopathology will be based on the study of patients, but also on animal models. This report summarizes our results obtained on the analysis of the deafness linked to aging on the C57/BL/6 mice.

  20. Mouse models and aging: longevity and progeria.

    PubMed

    Liao, Chen-Yu; Kennedy, Brian K

    2014-01-01

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

  1. The Podospora rmp1 gene implicated in nucleus-mitochondria cross-talk encodes an essential protein whose subcellular location is developmentally regulated.

    PubMed Central

    Contamine, Véronique; Zickler, Denise; Picard, Marguerite

    2004-01-01

    It has been previously reported that, at the time of death, the Podospora anserina AS1-4 mutant strains accumulate specific deleted forms of the mitochondrial genome and that their life spans depend on two natural alleles (variants) of the rmp1 gene: AS1-4 rmp1-2 strains exhibit life spans strikingly longer than those of AS1-4 rmp1-1. Here, we show that rmp1 is an essential gene. In silico analyses of eight rmp1 natural alleles present in Podospora isolates and of the putative homologs of this orphan gene in other filamentous fungi suggest that rmp1 evolves rapidly. The RMP1 protein is localized in the mitochondrial and/or the cytosolic compartment, depending on cell type and developmental stage. Strains producing RMP1 without its mitochondrial targeting peptide are viable but exhibit vegetative and sexual defects. PMID:15020413

  2. The Penna Model of Biological Aging

    PubMed Central

    Stauffer, D.

    2007-01-01

    This review deals with computer simulation of biological aging, particularly with the Penna model of 1995. They are based on the mutation accumulation theory of half a century ago. The results agree well with demographical reality, and also with the seemingly contradictory influence of predators on the aging of prey. PMID:20066128

  3. A Model of Spirituality for Ageing Muslims.

    PubMed

    Ahmad, Mahjabeen; Khan, Shamsul

    2016-06-01

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

  4. Species ages in neutral biodiversity models.

    PubMed

    Chisholm, Ryan A; O'Dwyer, James P

    2014-05-01

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

  5. Love Kills:. Simulations in Penna Ageing Model

    NASA Astrophysics Data System (ADS)

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

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

  6. Altered Mating-Type Identity in the Fungus Podospora Anserina Leads to Selfish Nuclei, Uniparental Progeny, and Haploid Meiosis

    PubMed Central

    Zickler, D.; Arnaise, S.; Coppin, E.; Debuchy, R.; Picard, M.

    1995-01-01

    In wild-type crosses of the filamentous ascomycete Podospora anserina, after fertilization, only nuclei of opposite mating type can form dikaryons that undergo karyogamy and meiosis, producing biparental progeny. To determine the role played by the mating type in these steps, the four mat genes were mutagenized in vitro and introduced into a strain deleted for its mat locus. Genetic and cytological analyses of these mutant strains, crossed to each other and to wild type, showed that mating-type information is required for recognition of nuclear identity during the early steps of sexual reproduction. In crosses with strains carrying a mating-type mutation, two unusual developmental patterns were observed: monokaryotic cells, resulting in haploid meiosis, and uniparental dikaryotic cells providing, after karyogamy and meiosis, a uniparental progeny. Altered mating-type identity leads to selfish behavior of the mutant nucleus: it migrates alone or paired, ignoring its wild-type partner in all mutant X wild-type crosses. This behavior is nucleus-autonomous because, in the same cytoplasm, the wild-type nuclei form only biparental dikaryons. In P. anserina, mat genes are thus required to ensure a biparental dikaryotic state but appear dispensable for later stages, such as meiosis and sporulation. PMID:7498731

  7. Co-expression of the mating-type genes involved in internuclear recognition is lethal in Podospora anserina.

    PubMed Central

    Coppin, E; Debuchy, R

    2000-01-01

    In the heterothallic filamentous fungus Podospora anserina, four mating-type genes encoding transcriptional factors have been characterized: FPR1 in the mat+ sequence and FMR1, SMR1, and SMR2 in the alternative mat- sequence. Fertilization is controlled by FPR1 and FMR1. After fertilization, male and female nuclei, which have divided in the same cell, form mat+/mat- pairs during migration into the ascogenous hyphae. Previous data indicate that the formation of mat+/mat- pairs is controlled by FPR1, FMR1, and SMR2. SMR1 was postulated to be necessary for initial development of ascogenous hyphae. In this study, we investigated the transcriptional control of the mat genes by seeking mat transcripts during the vegetative and sexual phase and fusing their promoter to a reporter gene. The data indicate that FMR1 and FPR1 are expressed in both mycelia and perithecia, whereas SMR1 and SMR2 are transcribed in perithecia. Increased or induced vegetative expression of the four mat genes has no effect when the recombined gene is solely in the wild-type strain. However, the combination of resident FPR1 with deregulated SMR2 and overexpressed FMR1 in the same nucleus is lethal. This lethality is suppressed by the expression of SMR1, confirming that SMR1 operates downstream of the other mat genes. PMID:10835389

  8. Altering a gene involved in nuclear distribution increases the repeat-induced point mutation process in the fungus Podospora anserina.

    PubMed Central

    Bouhouche, Khaled; Zickler, Denise; Debuchy, Robert; Arnaise, Sylvie

    2004-01-01

    Repeat-induced point mutation (RIP) is a homology-dependent gene-silencing mechanism that introduces C:G-to-T:A transitions in duplicated DNA segments. Cis-duplicated sequences can also be affected by another mechanism called premeiotic recombination (PR). Both are active over the sexual cycle of some filamentous fungi, e.g., Neurospora crassa and Podospora anserina. During the sexual cycle, several developmental steps require precise nuclear movement and positioning, but connections between RIP, PR, and nuclear distributions have not yet been established. Previous work has led to the isolation of ami1, the P. anserina ortholog of the Aspergillus nidulans apsA gene, which is required for nuclear positioning. We show here that ami1 is involved in nuclear distribution during the sexual cycle and that alteration of ami1 delays the fruiting-body development. We also demonstrate that ami1 alteration affects loss of transgene functions during the sexual cycle. Genetically linked multiple copies of transgenes are affected by RIP and PR much more frequently in an ami1 mutant cross than in a wild-type cross. Our results suggest that the developmental slowdown of the ami1 mutant during the period of RIP and PR increases time exposure to the duplication detection system and thus increases the frequency of RIP and PR. PMID:15166143

  9. Two NADPH oxidase isoforms are required for sexual reproduction and ascospore germination in the filamentous fungus Podospora anserina.

    PubMed

    Malagnac, Fabienne; Lalucque, Hervé; Lepère, Gersende; Silar, Philippe

    2004-11-01

    NADPH oxidases are enzymes that produce reactive oxygen species (ROS) using electrons derived from intracellular NADPH. In plants and mammals, ROS have been proposed to be second messengers that signal defence responses or cell proliferation. By inactivating PaNox1 and PaNox2, two genes encoding NADPH oxidases, we demonstrate the crucial role of these enzymes in the control of two key steps of the filamentous fungus Podospora anserina life cycle. PaNox1 mutants are impaired in the differentiation of fruiting bodies from their progenitor cells, and the deletion of the PaNox2 gene specifically blocks ascospore germination. Furthermore, we show that PaNox1 likely acts upstream of PaASK1, a MAPKKK previously implicated in stationary phase differentiation and cell degeneration. Using nitro blue tetrazolium (NBT) and diaminobenzidine (DAB) assays, we detect a regulated secretion of both superoxide and peroxide during P. anserina vegetative growth. In addition, two oxidative bursts are shown to occur during fruiting body development and ascospore germination. Analysis of mutants establishes that PaNox1, PaNox2, and PaASK1, as well as a still unknown additional source of ROS, modulate these secretions. Altogether, our data point toward a role for NADPH oxidases in signalling fungal developmental transitions with respect to nutrient availability. These enzymes are conserved in other multicellular eukaryotes, suggesting that early eukaryotes were endowed with a redox network used for signalling purposes.

  10. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  11. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

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

  12. Animal models of age related macular degeneration

    PubMed Central

    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

  13. Computational modeling of material aging effects

    SciTech Connect

    Fang, H.E.

    1996-07-01

    Progress is being made in our efforts to develop computational models for predicting material property changes in weapon components due to aging. The first version of a two-dimensional lattice code for modeling thermomechanical fatigue, such as has been observed in solder joints on electronic components removed from the stockpile, has been written and tested. The code does a good qualitative job of presenting intergranular and/or transgranular cracking in a polycrystalline material when under thermomechanical deformation. The current progress is an encouraging start for our long term effort to develop multi-level simulation capabilities, with the technology of high performance computing, for predicting age-related effects on the reliability of weapons.

  14. Aging, Breast Cancer and the Mouse Model

    DTIC Science & Technology

    2005-05-01

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

  15. Micromechanical Modeling of Concrete at Early Age

    NASA Astrophysics Data System (ADS)

    Tuleubekov, Kairat

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

  16. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  17. Creating Better School-Age Care Jobs: Model Work Standards.

    ERIC Educational Resources Information Center

    Haack, Peggy

    Built on the premise that good school-age care jobs are the cornerstone of high-quality services for school-age youth and their families, this guide presents model work standards for school-age care providers. The guide begins with a description of the strengths and challenges of the school-age care profession. The model work standards are…

  18. Speciation Effect in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

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

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

  19. Virginia Opossums, Minimum Reproduction Age and Predators in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

    Altevolmer, A. K.

    Age-specific predators are introduced into the Penna model of biological aging. It is shown that populations with a variable minimum reproduction age find a stable state with an earlier onset of reproduction, if older ages are eaten by the predators. This behavior agrees with the demographic data of the Virgina opossum.

  20. Evolutionary model with genetics, aging, and knowledge

    NASA Astrophysics Data System (ADS)

    Bustillos, Armando Ticona; de Oliveira, Paulo Murilo

    2004-02-01

    We represent a process of learning by using bit strings, where 1 bits represent the knowledge acquired by individuals. Two ways of learning are considered: individual learning by trial and error, and social learning by copying knowledge from other individuals or from parents in the case of species with parental care. The age-structured bit string allows us to study how knowledge is accumulated during life and its influence over the genetic pool of a population after many generations. We use the Penna model to represent the genetic inheritance of each individual. In order to study how the accumulated knowledge influences the survival process, we include it to help individuals to avoid the various death situations. Modifications in the Verhulst factor do not show any special feature due to its random nature. However, by adding years to life as a function of the accumulated knowledge, we observe an improvement of the survival rates while the genetic fitness of the population becomes worse. In this latter case, knowledge becomes more important in the last years of life where individuals are threatened by diseases. Effects of offspring overprotection and differences between individual and social learning can also be observed. Sexual selection as a function of knowledge shows some effects when fidelity is imposed.

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

    PubMed

    Ricklefs, Robert E; Scheuerlein, Alex

    2002-02-01

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

  2. Age-Of Dependent Mutation Rate and Weak Children in the Penna Model in Biological Ageing

    NASA Astrophysics Data System (ADS)

    Berntsen, K. Nikolaj

    We investigate the effect of an age-dependent mutation rate in the Penna model of ageing and then we observe that the high mortality for human babies can be reproduced by the model if one assumes babies to be weaker than adults.

  3. Computer Modelling of Age Hardening for Isothermally Aged Al-Mg-Si Alloys

    NASA Astrophysics Data System (ADS)

    Wu, Linda; Ferguson, W. George

    Computer modelling, due to it saving time and money, has been widely used in industrial simulation. The present model, which is based on the Shercliff-Ashby methodology for the ageing of aluminum alloys, can be used to predict the yield strength (or hardness) of Al-Mg-Si alloys for the artificial ageing temperature below the solvus temperature as a function of time. With suitable input data, this model can be applied to most Al-Mg-Si alloys, wrought or cast. In the present model, input data for aluminium alloys of A356, A357 and 6061 is taken from the open literature, and then the unknown constants are calibrated from these data. After calibration, the ageing curves are constructed for different isothermal ageing temperatures. Finally, experimentally ageing heat treatments at different temperatures for casting alloys of A356 were done to validate the model.

  4. Modeling Creep Processes in Aging Polymers

    NASA Astrophysics Data System (ADS)

    Olali, N. V.; Voitovich, L. V.; Zazimko, N. N.; Malezhik, M. P.

    2016-03-01

    The photoelastic method is generalized to creep in hereditary aging materials. Optical-creep curves and mechanical-creep or optical-relaxation curves are used to interpret fringe patterns. For materials with constant Poisson's ratio, it is sufficient to use mechanical- or optical-creep curves for this purpose

  5. Age Integrated Learning: A Theoretical Model.

    ERIC Educational Resources Information Center

    Heckenmueller, Jerome P.; Keller, Ann

    The concept of age integrated learning (AIL) can be derived from Erikson's theory of psychosocial development. Two emphases in his theory that are less well recognized than others are central to Erikson's theory and are the cornerstone of a rationale for AIL. The first is his emphasis on the interdependence of generations for optimal crisis…

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

    PubMed

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

    2015-03-01

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

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

    SciTech Connect

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

    2015-03-01

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

  8. An Age-Graded Model for Career Development Education.

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    This paper presents a career developmental model covering the ages of 5 to 18. Career development education includes experiences which facilitate self-awareness, career-awareness and career decision-making. Before choosing a model for career development, it is necessary to decide on a model for child development. The model developed here borrows…

  9. An integrated modeling approach to age invariant face recognition

    NASA Astrophysics Data System (ADS)

    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.

  10. Exploring the power of yeast to model aging and age-related neurodegenerative disorders.

    PubMed

    Oliveira, Ana V; Vilaça, Rita; Santos, Cláudia N; Costa, Vítor; Menezes, Regina

    2017-02-01

    Aging is a multifactorial process determined by molecular, cellular and systemic factors and it is well established that advancing age is a leading risk factor for several neurodegenerative diseases. In fact, the close association of aging and neurodegenerative disorders has placed aging as the greatest social and economic challenge of the 21st century, and age-related diseases have also become a key priority for countries worldwide. The growing need to better understand both aging and neurodegenerative processes has led to the development of simple eukaryotic models amenable for mechanistic studies. Saccharomyces cerevisiae has proven to be an unprecedented experimental model to study the fundamental aspects of aging and to decipher the intricacies of neurodegenerative disorders greatly because the molecular mechanisms underlying these processes are evolutionarily conserved from yeast to human. Moreover, yeast offers several methodological advantages allowing a rapid and relatively easy way of establishing gene-protein-function associations. Here we review different aging theories, common cellular pathways driving aging and neurodegenerative diseases and discuss the major contributions of yeast to the state-of-art knowledge in both research fields.

  11. Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

    PubMed

    Dubeau, S; Ferland, G; Gaudreau, P; Beaumont, E; Lesage, F

    2011-06-15

    The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  13. A comprehensive approach to age-dependent dosimetric modeling

    SciTech Connect

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Econometric model for age- and population-dependent radiation exposures

    SciTech Connect

    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.

  17. Probabilistically Constraining Age-Depth-Models of Glaciogenic Sediments

    NASA Astrophysics Data System (ADS)

    Werner, J.; van der Bilt, W.; Tingley, M.

    2015-12-01

    Reconstructions of the late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting. All of these proxies, such as measurements of tree rings, ice cores, and varved lake sediments do carry some inherent dating uncertainty that is not always fully accounted for. Considerable advances could be achieved if time uncertainties were recognized and correctly modeled, also for proxies commonly treated as free of age model errors. Current approaches for accounting for time uncertainty are generally limited to repeating the reconstruction using each one of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Werner and Tingley (2015) demonstrated how Bayesian hierarchical climate reconstruction models can be augmented to account for time-uncertain proxies. In their method, probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments (Werner and Tingley 2015) show that updating the age model probabilities decreases uncertainty in the resulting reconstructions, as compared with the current de facto standard of sampling over all age models, provided there is sufficient information from other data sources in the spatial region of the time-uncertain proxy. We show how this novel method can be applied to high resolution, sub-annually sampled lacustrine sediment records to constrain their respective age depth models. The results help to quantify the signal content and extract the regionally representative signal. The single time series can then be used as the basis for a reconstruction of glacial activity. van der Bilt et al. in prep. Werner, J.P. and Tingley, M.P. Clim. Past (2015)

  18. Multiscale Concrete Modeling of Aging Degradation

    SciTech Connect

    Hammi, Yousseff; Gullett, Philipp; Horstemeyer, Mark F.

    2015-07-31

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

  19. Housekeeping Genes and Death Genes in the Penna Aging Model

    NASA Astrophysics Data System (ADS)

    Niewczas, E.; Kurdziel, A.; Cebrat, S.

    The Penna model of aging predicts the accumulation of defective genes expressed after the organism reaches the minimum reproduction age in the genetic pool of the population. The accumulation of defects in the genomes implicates the specific age structure of the modeled populations. Nevertheless, the fraction of defective alleles at loci switched on before the reproduction period does not depend on exact age when precisely they are switched on, it may be just after conception or after birth. We have modeled the mortality of a population in the period before the minimum reproduction age, even before birth, assuming that sets of genes of different size are switched on in different periods of the life span.

  20. Selection Experiments in the Penna Model for Biological Aging

    NASA Astrophysics Data System (ADS)

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

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

  1. Travelling Wave Solutions in Multigroup Age-Structured Epidemic Models

    NASA Astrophysics Data System (ADS)

    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.

  2. Aging mechanism in model Pickering emulsion

    NASA Astrophysics Data System (ADS)

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

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

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

    USGS Publications Warehouse

    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.

  4. ami1, an orthologue of the Aspergillus nidulans apsA gene, is involved in nuclear migration events throughout the life cycle of Podospora anserina.

    PubMed Central

    Graïa, F; Berteaux-Lecellier, V; Zickler, D; Picard, M

    2000-01-01

    The Podospora anserina ami1-1 mutant was identified as a male-sterile strain. Microconidia (which act as male gametes) form, but are anucleate. Paraphysae from the perithecium beaks are also anucleate when ami1-1 is used as the female partner in a cross. Furthermore, in crosses heterozygous for ami1-1, some crozier cells are uninucleate rather than binucleate. In addition to these nuclear migration defects, which occur at the transition between syncytial and cellular states, ami1-1 causes abnormal distribution of the nuclei in both mycelial filaments and asci. Finally, an ami1-1 strain bearing information for both mating types is unable to self-fertilize. The ami1 gene is an orthologue of the Aspergillus nidulans apsA gene, which controls nuclear positioning in filaments and during conidiogenesis (at the syncytial/cellular transition). The ApsA and AMI1 proteins display 42% identity and share structural features. The apsA gene complements some ami1-1 defects: it increases the percentage of nucleate microconidia and restores self-fertility in an ami1-1 mat+ (mat-) strain. The latter effect is puzzling, since in apsA null mutants sexual reproduction is quite normal. The functional differences between the two genes are discussed with respect to their possible history in these two fungi, which are very distant in terms of evolution. PMID:10835387

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

    PubMed Central

    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

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

    PubMed Central

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

    1998-01-01

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

  7. Identification of six loci in which mutations partially restore peroxisome biogenesis and/or alleviate the metabolic defect of pex2 mutants in podospora.

    PubMed Central

    Ruprich-Robert, Gwenaël; Berteaux-Lecellier, Véronique; Zickler, Denise; Panvier-Adoutte, Arlette; Picard, Marguerite

    2002-01-01

    Peroxins (PEX) are proteins required for peroxisome biogenesis. Mutations in PEX genes cause lethal diseases in humans, metabolic defects in yeasts, and developmental disfunctions in plants and filamentous fungi. Here we describe the first large-scale screening for suppressors of a pex mutation. In Podospora anserina, pex2 mutants exhibit a metabolic defect [inability to grow on medium containing oleic acid (OA medium) as sole carbon source] and a developmental defect (inability to differentiate asci in homozygous crosses). Sixty-three mutations able to restore growth of pex2 mutants on OA medium have been analyzed. They fall in six loci (suo1 to suo6) and act as dominant, allele-nonspecific suppressors. Most suo mutations have pleiotropic effects in a pex2(+) background: formation of unripe ascospores (all loci except suo5 and suo6), impaired growth on OA medium (all loci except suo4 and suo6), or sexual defects (suo4). Using immunofluorescence and GFP staining, we show that peroxisome biogenesis is partially restored along with a low level of ascus differentiation in pex2 mutant strains carrying either the suo5 or the suo6 mutations. The data are discussed with respect to beta-oxidation of fatty acids, peroxisome biogenesis, and cell differentiation. PMID:12136013

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

    PubMed

    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.

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

    PubMed

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

    2009-03-01

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

  10. Exact solution of an evolutionary model without aging.

    PubMed

    Onody, R N; de Medeiros, N G

    1999-09-01

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

  11. Exact solution of an evolutionary model without aging

    NASA Astrophysics Data System (ADS)

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

    1999-09-01

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

  12. The development of small primate models for aging research.

    PubMed

    Fischer, Kathleen E; Austad, Steven N

    2011-01-01

    Nonhuman primate (NHP) aging research has traditionally relied mainly on the rhesus macaque. But the long lifespan, low reproductive rate, and relatively large body size of macaques and related Old World monkeys make them less than ideal models for aging research. Manifold advantages would attend the use of smaller, more rapidly developing, shorter-lived NHP species in aging studies, not the least of which are lower cost and the ability to do shorter research projects. Arbitrarily defining "small" primates as those weighing less than 500 g, we assess small, relatively short-lived species among the prosimians and callitrichids for suitability as models for human aging research. Using the criteria of availability, knowledge about (and ease of) maintenance, the possibility of genetic manipulation (a hallmark of 21st century biology), and similarities to humans in the physiology of age-related changes, we suggest three species--two prosimians (Microcebus murinus and Galago senegalensis) and one New World monkey (Callithrix jacchus)--that deserve scrutiny for development as major NHP models for aging studies. We discuss one other New World monkey group, Cebus spp., that might also be an effective NHP model of aging as these species are longer-lived for their body size than any primate except humans.

  13. The heuristic value of redundancy models of aging.

    PubMed

    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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. Invertebrates as model organisms for research on aging biology

    PubMed Central

    Murthy, Mahadev; Ram, Jeffrey L.

    2015-01-01

    Invertebrate model systems, such as nematodes and fruit flies, have provided valuable information about the genetics and cellular biology involved in aging. However, limitations of these simple, genetically tractable organisms suggest the need for other model systems, some of them invertebrate, to facilitate further advances in the understanding of mechanisms of aging and longevity in mammals, including humans. This paper introduces 10 review articles about the use of invertebrate model systems for the study of aging by authors who participated in an ‘NIA-NIH symposium on aging in invertebrate model systems’ at the 2013 International Congress for Invertebrate Reproduction and Development. In contrast to the highly derived characteristics of nematodes and fruit flies as members of the superphylum Ecdysozoa, cnidarians, such as Hydra, are more ‘basal’ organisms that have a greater number of genetic orthologs in common with humans. Moreover, some other new model systems, such as the urochordate Botryllus schlosseri, the tunicate Ciona, and the sea urchins (Echinodermata) are members of the Deuterostomia, the same superphylum that includes all vertebrates, and thus have mechanisms that are likely to be more closely related to those occurring in humans. Additional characteristics of these new model systems, such as the recent development of new molecular and genetic tools and a more similar pattern to humans of regeneration and stem cell function suggest that these new model systems may have unique advantages for the study of mechanisms of aging and longevity. PMID:26241448

  17. Age and equity in liver transplantation: An organ allocation model.

    PubMed

    Cucchetti, Alessandro; Ross, Lainie Friedman; Thistlethwaite, J Richard; Vitale, Alessandro; Ravaioli, Matteo; Cescon, Matteo; Ercolani, Giorgio; Burra, Patrizia; Cillo, Umberto; Pinna, Antonio Daniele

    2015-10-01

    A moral liver allocation policy must be fair. We considered a 2-step, 2-principle allocation system called "age mapping." Its first principle, equal opportunity, ensures that candidates of all ages have an equal chance of getting an organ. Its second principle, prudential lifespan equity, allocates younger donor grafts to younger candidates and older donors to older candidates in order to increase the likelihood that all recipients achieve a "full lifespan." Data from 2476 candidates and 1371 consecutive adult liver transplantations (from 1999 to 2012) were used to determine whether age mapping can reduce the gap in years of life lost (YLL) between younger and older recipients. A parametric Weibull prognostic model was developed to estimate total life expectancy after transplantation using survival of the general population matched by sex and age as a reference. Life expectancy from birth was calculated by adding age at transplant and total life expectancy after transplantation. In multivariate analysis, recipient age, hepatitis C virus status, Model for End-Stage Liver Disease score at transplant of >30, and donor age were significantly related to prognosis after surgery (P < 0.05). The mean (and standard deviation) number of years of life from birth, calculated from the current allocation model, for various age groups were: recipients 18-47 years (n = 340) = 65.2 (3.3); 48-55 years (n = 387) = 72.7 (2.1); 56-61 years (n = 372) = 74.7 (1.7) and for recipients >61 years (n = 272) = 77.4 (1.4). The total number of YLL equaled 523 years. Redistributing liver grafts, using an age mapping algorithm, reduces the lifespan gap between younger and older candidates by 33% (from 12.3% to 8.3%) and achieves a 14% overall reduction of YLL (73 years) compared to baseline liver distribution. In conclusion, deliberately incorporating age into an allocation algorithm promotes fairness and increases efficiency.

  18. Active Ageing: An Empirical Approach to the WHO Model

    PubMed Central

    Paúl, Constança; Ribeiro, Oscar; Teixeira, Laetitia

    2012-01-01

    Background. In the beginning of the 21st century, the world summit on population taking place in Madrid approved active ageing, WHO (2002) as the main objective of health and social policies for old people. Few studies have been done on the scientific validity of the construct. This study aims to validate the construct of active ageing and test empirically the WHO (2002) model of Active Ageing in a sample of community-dwelling seniors. Methods. 1322 old people living in the community were interviewed using an extensive assessment protocol to measure WHO's determinants of active ageing and performed an exploratory factor analysis followed by a confirmatory factor analyses. Results. We did not confirm the active ageing model, as most of the groups of determinants are either not independent or not significant. We got to a six-factor model (health, psychological component, cognitive performance, social relationships, biobehavioural component, and personality) explaining 54.6% of total variance. Conclusion. The present paper shows that there are objective as well as subjective variables contributing to active ageing and that psychological variables seem to give a very important contribute to the construct. The profile of active ageing is expected to vary between contexts and cultures and can be used to guide specific community and individually based interventions. PMID:23193396

  19. "Oxygen supply" as modulator of aging processes: hypoxia and hyperoxia models for aging studies.

    PubMed

    Cataldi, Amelia; Di Giulio, Camillo

    2009-07-01

    Cell growth is regulated by several factors, including oxygen supply, which influence cell metabolism. Aging is characterized by decreased oxygen supply to tissue, a reduction of tissue PO(2) and of the activity of several enzymes and metabolic factors. The oxygen-gradient diffusion at capillary tissue level is essential for the cellular survival, while the homeostasis of the oxygen in the arterial blood is mediated by reflexes sensitive to oxygen decrease and by release of several factors. Aging is correlated with a reduction of cells' oxygen supply concomitant to a parallel decrease in oxygen demand by tissues. Both chronic hypoxia or hyperoxia are considered as stresses. Indeed, in both conditions, free radical species, which damage structural and functional components of the membrane, are generated. ROS (reactive oxygen species) are physiological products of aerobic life and their accumulation affects aging. Because hypoxia per se modulates mitochondria activity, influencing oxygen consumption, hypoxia and aging could share some link. Moreover, the observation that in hypoxia or hyperoxia there is an accumulation of lipofucsine as a general reaction to stress is consistent with the accumulation of such components during aging. Correlation between hypoxia-hyperoxia and life-span remains open until we solve the question of how and why do cells sense oxygen. In other words, to better understand aging we need to know what O(2) species are being sensed by cells. In conclusion, hypoxia and hyperoxia represent an experimental model adequate for studying aging processes.

  20. Age Dependent Absolute Plate and Plume Motion Modeling

    NASA Astrophysics Data System (ADS)

    Heaton, D. E.; Koppers, A. A. P.

    2015-12-01

    Current absolute plate motion (APM) models from 80 - 0 Ma are constrained by the location of mantle plume related hotspot seamounts, in particular those of the Hawaiian-Emperor and Louisville seamount trails. Originally the 'fixed' hotspot hypothesis was developed to explain past plate motion based on linear age progressive intra-plate volcanism. However, now that 'moving' hotspots are accepted, it is becoming clear that APM models need to be corrected for individual plume motion vectors. For older seamount trails that were active between roughly 50 and 80 Ma the APM models that use 'fixed' hotspots overestimate the measured age progression in those trails, while APM models corrected for 'moving' hotspots underestimate those age progressions. These mismatches are due to both a lack of reliable ages in the older portions of both the Hawaii and Louisville seamount trails and insufficient APM modeling constraints from other seamount trails in the Pacific Basin. Seamounts are difficult to sample and analyze because many are hydrothermally altered and have low potassium concentrations. New 40Ar/39Ar Age results from International Ocean Drilling Project (IODP) Expedition 330 Sites U1372 (n=18), U1375 (n=3), U1376 (n=15) and U1377 (n=7) aid in constraining the oldest end of the Louisville Seamount trail. A significant observation in this study is that the age range recovered in the drill cores match the range of ages that were acquired on dredging cruises at the same seamounts (e.g. Koppers et al., 2011). This is important for determining the inception age of a seamount. The sections recovered from IODP EXP 330 are in-situ volcanoclastic breccia and lava flows. Comparing the seismic interpretations of Louisville guyots (Contreras-Reyes et al., 2010), Holes U1372, U1373 and U1374 penetrated the extrusive and volcanoclastic sections of the seamount. The ages obtained are consistent over stratigraphic intervals >100-450 m thick, providing evidence that these seamounts

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

    PubMed

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

    2016-07-01

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

  2. Justification of sexual reproduction by modified Penna model of ageing

    NASA Astrophysics Data System (ADS)

    Sá Martins, J. S.; Stauffer, D.

    2001-05-01

    We generalize the standard Penna bit-string model of biological ageing by assuming that each deleterious mutation diminishes the survival probability in every time interval by a small percentage. This effect is added to the usual lethal but age-dependent effect of the same mutation. We then find strong advantages or disadvantages of sexual reproduction (with males and females) compared to asexual cloning, depending on parameters.

  3. Age-dependent forest carbon sink: Estimation via inverse modeling

    NASA Astrophysics Data System (ADS)

    Zhou, Tao; Shi, Peijun; Jia, Gensuo; Dai, Yongjiu; Zhao, Xiang; Shangguan, Wei; Du, Ling; Wu, Hao; Luo, Yiqi

    2015-12-01

    Forests have been recognized to sequester a substantial amount of carbon (C) from the atmosphere. However, considerable uncertainty remains regarding the magnitude and time course of the C sink. Revealing the intrinsic relationship between forest age and C sink is crucial for reducing uncertainties in prediction of forest C sink potential. In this study, we developed a stepwise data assimilation approach to combine a process-based Terrestrial ECOsystem Regional model, observations from multiple sources, and stochastic sampling to inversely estimate carbon cycle parameters including carbon sink at different forest ages for evergreen needle-leaved forests in China. The new approach is effective to estimate age-dependent parameter of maximal light-use efficiency (R2 = 0.99) and, accordingly, can quantify a relationship between forest age and the vegetation and soil C sinks. The estimated ecosystem C sink increases rapidly with age, peaks at 0.451 kg C m-2 yr-1 at age 22 years (ranging from 0.421 to 0.465 kg C m-2 yr-1), and gradually decreases thereafter. The dynamic patterns of C sinks in vegetation and soil are significantly different. C sink in vegetation first increases rapidly with age and then decreases. C sink in soil, however, increases continuously with age; it acts as a C source when the age is less than 20 years, after which it acts as a sink. For the evergreen needle-leaved forest, the highest C sink efficiency (i.e., C sink per unit net primary productivity) is approximately 60%, with age between 11 and 43 years. Overall, the inverse estimation of carbon cycle parameters can make reasonable estimates of age-dependent C sequestration in forests.

  4. Tuberculosis in Cape Town: an age-structured transmission model

    PubMed Central

    Blaser, Nello; Zahnd, Cindy; Hermans, Sabine; Salazar-Vizcaya, Luisa; Estill, Janne; Morrow, Carl; Egger, Matthias; Keiser, Olivia; Wood, Robin

    2015-01-01

    Background Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24 and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. Methods We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. Results The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1,000/100,000 person-years (pyrs) in children aged < 5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. Conclusion The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients

  5. Cellular senescence in the Penna model of aging

    NASA Astrophysics Data System (ADS)

    Periwal, Avikar

    2013-11-01

    Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

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

    USGS Publications Warehouse

    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

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

    USGS Publications Warehouse

    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.

  8. Past and recent attempts to model mortality at all ages.

    PubMed

    Hartmann, M

    1987-01-01

    "Most laws of mortality are partial in the sense that they apply only to a broad age group and not to all ages. This paper focuses on three laws of mortality that apply to all ages. Two of them were developed by the actuaries Thiele and Wittstein in the late 19th century. The third, developed by Heligman and Pollard, is of recent origin. The three laws are discussed with references to Scandinavian mortality data. The results suggest that the most recently proposed law can be used for generation of model life tables, for making population projections, simulations, and other statistical work where there is a need for a realistic model of human mortality."

  9. Computer modelling of age hardening for cast aluminium alloys

    NASA Astrophysics Data System (ADS)

    Wu, Linda; Ferguson, W. George

    2009-08-01

    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.

  10. Age of stratospheric air and aging by mixing in global models

    NASA Astrophysics Data System (ADS)

    Garny, Hella; Dietmüller, Simone; Plöger, Felix; Birner, Thomas; Bönisch, Harald; Jöckel, Patrick

    2016-04-01

    The Brewer-Dobson circulation is often quantified by the integrated transport measure age of air (AoA). AoA is affected by all transport processes, including transport along the residual mean mass circulation and two-way mixing. A large spread in the simulation of AoA by current global models exists. Using CCMVal-2 and CCMI-1 global model data, we show that this spread can only in small parts be attributed to differences in the simulated residual circulation. Instead, large differences in the "mixing efficiency" strongly contribute to the differences in the simulated AoA. The "mixing efficiency" is defined as the ratio of the two-way mixing mass flux across the subtropical barrier to the net (residual) mass flux, and this mixing efficiency controls the relative increase in AoA by mixing. We derive the mixing efficiency from global model data using the analytical solution of a simplified version of the tropical leaky pipe (TLP) model, in which vertical diffusion is neglected. Thus, it is assumed that only residual mean transport and horizontal two-way mixing across the subtropical barrier controls AoA. However, in global models vertical mixing and numerical diffusion modify AoA, and these processes likely contribute to the differences in the mixing efficiency between models. We explore the contributions of diffusion and mixing on mean AoA by a) using simulations with the tropical leaky pipe model including vertical diffusion and b) explicit calculations of aging by mixing on resolved scales. Using the TLP model, we show that vertical diffusion leads to a decrease in tropical AoA, i.e. counteracts the increase in tropical mean AoA due to horizontal mixing. Thus, neglecting vertical diffusion leads to an underestimation of the mixing efficiency. With explicit calculations of aging by mixing via integration of daily local mixing tendencies along residual circulation trajectories, we explore the contributions of vertical and horizontal mixing for aging by mixing. The

  11. Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, Johannes; Tingley, Martin

    2015-04-01

    Reconstructions of late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurement on tree rings, ice cores, and varved lake sediments. Considerable advances may be achievable if time uncertain proxies could be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches to accounting for time uncertainty are generally limited to repeating the reconstruction using each of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here we demonstrate how Bayesian Hierarchical climate reconstruction models can be augmented to account for time uncertain proxies. Critically, while a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age model probabilities decreases uncertainty in the climate reconstruction, as compared with the current de-facto standard of sampling over all age models, provided there is sufficient information from other data sources in the region of the time-uncertain proxy. This approach can readily be generalized to non-layer counted proxies, such as those derived from marine sediments. Werner and Tingley, Climate of the Past Discussions (2014)

  12. Technical Note: Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, J. P.; Tingley, M. P.

    2015-03-01

    Reconstructions of the late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurements of tree rings, ice cores, and varved lake sediments. Considerable advances could be achieved if time-uncertain proxies were able to be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches for accounting for time uncertainty are generally limited to repeating the reconstruction using each one of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here, we demonstrate how Bayesian hierarchical climate reconstruction models can be augmented to account for time-uncertain proxies. Critically, although a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age model probabilities decreases uncertainty in the resulting reconstructions, as compared with the current de facto standard of sampling over all age models, provided there is sufficient information from other data sources in the spatial region of the time-uncertain proxy. This approach can readily be generalized to non-layer-counted proxies, such as those derived from marine sediments.

  13. Technical Note: Probabilistically constraining proxy age-depth models within a Bayesian hierarchical reconstruction model

    NASA Astrophysics Data System (ADS)

    Werner, J. P.; Tingley, M. P.

    2014-12-01

    Reconstructions of late-Holocene climate rely heavily upon proxies that are assumed to be accurately dated by layer counting, such as measurement on tree rings, ice cores, and varved lake sediments. Considerable advances may be achievable if time uncertain proxies could be included within these multiproxy reconstructions, and if time uncertainties were recognized and correctly modeled for proxies commonly treated as free of age model errors. Current approaches to accounting for time uncertainty are generally limited to repeating the reconstruction using each of an ensemble of age models, thereby inflating the final estimated uncertainty - in effect, each possible age model is given equal weighting. Uncertainties can be reduced by exploiting the inferred space-time covariance structure of the climate to re-weight the possible age models. Here we demonstrate how Bayesian Hierarchical climate reconstruction models can be augmented to account for time uncertain proxies. Critically, while a priori all age models are given equal probability of being correct, the probabilities associated with the age models are formally updated within the Bayesian framework, thereby reducing uncertainties. Numerical experiments show that updating the age-model probabilities decreases uncertainty in the climate reconstruction, as compared with the current de-facto standard of sampling over all age models, provided there is sufficient information from other data sources in the region of the time-uncertain proxy. This approach can readily be generalized to non-layer counted proxies, such as those derived from marine sediments.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

    Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmax<1 . The value of fmax in observational studies appears to be nonuniversal, but fmax≈0.7 is often reported. A previously developed network model of individual aging was unable to recover fmax<1 while retaining the other observed phenomenology of increasing f and mortality rates with age. We have developed a computationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q <1 , and this degradation is mitigated when increasing number of deficits are included in the FI. We also find that the information spectrum, i.e., the mutual information of individual deficits versus connectivity, has an approximately power-law dependence that depends on the network exponent α . Mutual information I is therefore a useful tool for characterizing the network topology of aging populations.

  15. Rotifers as models for the biology of aging.

    PubMed

    Snell, Terry W

    2014-03-01

    It has been two decades since 1993 when research on the biology of rotifer aging was last reviewed by Enesco. Much has transpired during this time as rotifer biologists have adapted to the "omics" revolution and incorporated these techniques into the experimental analysis of rotifers. Rotifers are amenable to many of these approaches and getting adequate quantities of DNA, RNA, and protein from rotifers is not difficult. Analysis of rotifer genomes, transcriptomes, and proteomes is rapidly yielding candidate genes that likely regulate a variety of features of rotifer biology. Parallel developments in aging biology have recognized the limitations of standard animal models like worms and flies and that comparative aging research has essentially ignored a large fraction of animal phylogeny in the lophotrochozoans. As experimentally tractable members of this group, rotifers have attracted interest as models of aging. In this paper, I review advances over the past 20 years in the biology of aging in rotifers, with emphasis on the unique contributions of rotifer models for understanding aging. The majority of experimental work has manipulated rotifer diet and followed changes in survival and reproductive dynamics like mean lifespan, maximum lifespan, reproductive lifespan, and mortality rate doubling time. The main dietary manipulation has been some form of caloric restriction, withholding food for some period or feeding continuously at low levels. There have been comparative studies of several rotifer species, with some species responding to caloric restriction with life extension, but others not, at least under the tested food regimens. Other aspects of diet are less explored, like nutritional properties of different algae species and their capacity to extend rotifer lifespan. Several descriptive studies have reported many genes involved in rotifer aging by comparing gene expression in young and old individuals. Classes of genes up or down-regulated during aging have

  16. Rotifers as models for the biology of aging

    PubMed Central

    Snell, Terry W.

    2013-01-01

    It has been two decades since 1993 when research on the biology of rotifer aging was last reviewed by Enesco. Much has transpired during this time as rotifer biologists have adapted to the “omics” revolution and incorporated these techniques into the experimental analysis of rotifers. Rotifers are amenable to many of these approaches and getting adequate quantities of DNA, RNA, and protein from rotifers is not difficult. Analysis of rotifer genomes, transcriptomes, and proteomes is rapidly yielding candidate genes that likely regulate a variety of features of rotifer biology. Parallel developments in aging biology have recognized the limitations of standard animal models like worms and flies and that comparative aging research has essentially ignored a large fraction of animal phylogeny in the lophotrochozoans. As experimentally tractable members of this group, rotifers have attracted interest as models of aging. In this paper, I review advances over the past 20 years in the biology of aging in rotifers, with emphasis on the unique contributions of rotifer models for understanding aging. The majority of experimental work has manipulated rotifer diet and followed changes in survival and reproductive dynamics like mean lifespan, maximum lifespan, reproductive lifespan, and mortality rate doubling time. The main dietary manipulation has been some form of caloric restriction, withholding food for some period or feeding continuously at low levels. There have been comparative studies of several rotifer species, with some species responding to caloric restriction with life extension, but others not, at least under the tested food regimens. Other aspects of diet are less explored, like nutritional properties of different algae species and their capacity to extend rotifer lifespan. Several descriptive studies have reported many genes involved in rotifer aging by comparing gene expression in young and old individuals. Classes of genes up or down-regulated during aging

  17. Integrated modelling of age and sex patterns of European migration.

    PubMed

    Wiśniowski, Arkadiusz; Forster, Jonathan J; Smith, Peter W F; Bijak, Jakub; Raymer, James

    2016-10-01

    Age and sex patterns of migration are essential for understanding drivers of population change and heterogeneity of migrant groups. We develop a hierarchical Bayesian model to estimate such patterns for international migration in the European Union and European Free Trade Association from 2002 to 2008, which was a period of time when the number of members expanded from 19 to 31 countries. Our model corrects for the inadequacies and inconsistencies in the available data and estimates the missing patterns. The posterior distributions of the age and sex profiles are then combined with a matrix of origin-destination flows, resulting in a synthetic database with measures of uncertainty for migration flows and other model parameters.

  18. Aging, Neurogenesis, and Caloric Restriction in Different Model Organisms

    PubMed Central

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

    2013-01-01

    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. PMID:23936746

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

    PubMed

    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.

  20. Revisiting dark energy models using differential ages of galaxies

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  1. Modelling safety of multistate systems with ageing components

    NASA Astrophysics Data System (ADS)

    Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna

    2016-06-01

    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.

  2. Scaling in a Continuous Time Model for Biological Aging

    NASA Astrophysics Data System (ADS)

    de Almeida, R. M. C.; Thomas, G. L.

    In this paper, we consider a generalization to the asexual version of Penna model for biological aging, where we take a continuous time limit. The genotype associated to each individual is an interval of real numbers over which Dirac δ-functions are defined, representing genetically programmed diseases to be switched on at defined ages of the individual life. We discuss two different continuous limits for the evolution equation and two different mutation protocols, to be implemented during reproduction. Exact stationary solutions are obtained and scaling properties are discussed.

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

    PubMed

    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.

  4. Estimating child mortality and modelling its age pattern for India.

    PubMed

    Roy, S G

    1989-06-01

    "Using data [for India] on proportions of children dead...estimates of infant and child mortality are...obtained by Sullivan and Trussell modifications of [the] Brass basic method. The estimate of child survivorship function derived after logit smoothing appears to be more reliable than that obtained by the Census Actuary. The age pattern of childhood mortality is suitably modelled by [a] Weibull function defining the probability of surviving from birth to a specified age and involving two parameters of level and shape. A recently developed linearization procedure based on [a] graphical approach is adopted for estimating the parameters of the function."

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

    SciTech Connect

    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.

  6. Impact of aging mechanism on model simulated carbonaceous aerosols

    PubMed Central

    Huang, Y.; Wu, S.; Dubey, M.K.; French, N. H. F.

    2013-01-01

    Carbonaceous aerosols including organic carbon and black carbon have significant implications for both climate and air quality. In the current global climate or chemical transport models, a fixed hydrophobic-to-hydrophilic conversion lifetime for carbonaceous aerosol (τ) is generally assumed, which is usually around one day. We have implemented a new detailed aging scheme for carbonaceous aerosols in a chemical transport model (GEOS-Chem) to account for both the chemical oxidation and the physical condensation-coagulation effects, where τ is affected by local atmospheric environment including atmospheric concentrations of water vapor, ozone, hydroxyl radical and sulfuric acid. The updated τ exhibits large spatial and temporal variations with the global average (up to 11 km altitude) calculated to be 2.6 days. The chemical aging effects are found to be strongest over the tropical regions driven by the low ozone concentrations and high humidity there. The τ resulted from chemical aging generally decreases with altitude due to increases in ozone concentration and decreases in humidity. The condensation-coagulation effects are found to be most important for the high-latitude areas, in particular the polar regions, where the τ values are calculated to be up to 15 days. When both the chemical aging and condensation-coagulation effects are considered, the total atmospheric burdens and global average lifetimes of BC, black carbon, (OC, organic carbon) are calculated to increase by 9% (3%) compared to the control simulation, with considerable enhancements of BC and OC concentrations in the Southern Hemisphere. Model evaluations against data from multiple datasets show that the updated aging scheme improves model simulations of carbonaceous aerosols for some regions, especially for the remote areas in the Northern Hemisphere. The improvement helps explain the persistent low model bias for carbonaceous aerosols in the Northern Hemisphere reported in literature. Further

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

    PubMed

    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.

  8. Geophysical Age Dating of Seamounts using Dense Core Flexure Model

    NASA Astrophysics Data System (ADS)

    Hwang, Gyuha; Kim, Seung-Sep

    2016-04-01

    Lithospheric flexure of oceanic plate is thermo-mechanical response of an elastic plate to the given volcanic construct (e.g., seamounts and ocean islands). If the shape and mass of such volcanic loads are known, the flexural response is governed by the thickness of elastic plate, Te. As the age of oceanic plate increases, the elastic thickness of oceanic lithosphere becomes thicker. Thus, we can relate Te with the age of plate at the time of loading. To estimate the amount of the driving force due to seamounts on elastic plate, one needs to approximate their density structure. The most common choice is uniform density model, which utilizes constant density value for a seamount. This approach simplifies computational processes for gravity prediction and error estimates. However, the uniform density model tends to overestimate the total mass of the seamount and hence produces more positive gravitational contributions from the load. Minimization of gravity misfits using uniform density, therefore, favors thinner Te in order to increase negative contributions from the lithospheric flexure, which can compensate for the excessive positives from the seamount. An alternative approach is dense core model, which approximate the heterogeneity nature of seamount density as three bodies of infill sediment, edifice, and dense core. In this study, we apply the dense core model to the Louisville Seamount Chain for constraining flexural deformation. We compare Te estimates with the loading time of the examined seamounts to redefine empirical geophysical age dating of seamounts.

  9. Automatic age and gender classification using supervised appearance model

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  10. Nothobranchius as a model for aging studies. A review

    PubMed Central

    Lucas-Sánchez, Alejandro; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

    2014-01-01

    In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging. PMID:25110612

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  12. Autophagy and ageing: insights from invertebrate model organisms.

    PubMed

    Lionaki, Eirini; Markaki, Maria; Tavernarakis, Nektarios

    2013-01-01

    Ageing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing. Indeed, loss of autophagy gene function significantly influences longevity. Moreover, genetic or pharmacological manipulations that extend lifespan in model organisms often activate autophagy. Interestingly, conserved signalling pathways and environmental factors that regulate ageing, such as the insulin/IGF-1 signalling pathway and oxidative stress response pathways converge on autophagy. In this article, we survey recent findings in invertebrates that contribute to advance our understanding of the molecular links between autophagy and the regulation of ageing. In addition, we consider related mechanisms in other organisms and discuss their similarities and idiosyncratic features in a comparative manner.

  13. Annual fish as a genetic model for aging.

    PubMed

    Herrera, Michael; Jagadeeswaran, Pudur

    2004-02-01

    Advancement in the genetics of aging and identification of longevity genes has been largely due to the model organisms such as Caenorhabditis elegans and Drosophila melanogaster. However, knowledge gained from these invertebrates will not be able to identify vertebrate-specific longevity genes. The mouse has a relatively long life span of about 3 years, which limits its utility for screening of longevity genes. Fish have been used in aging studies. However, systematic comparison of survivorship curves for fish is lacking. In this study, we compared the survivorship curves of zebrafish and 2 different annual fish, namely, Cynolebias nigripinnis and Nothobranchius rachovii. These studies established that Nothobranchius rachovii has the shortest life span (8.5 months, at which time 10% of population remains). We also established that it is possible to breed Nothobranchius rachovii under laboratory conditions, and showed that their embryos can be stored for several months and hatched at any time by adding water. In addition, we have isolated 31 cDNA markers out of 71 attempted amplifications based on corresponding homologous genomic sequences in zebrafish and Fugu available from public databases, suggesting that approximately 40% of the genes from Nothobranchius rachovii could be easily isolated. Thus, the ability to be bred under laboratory conditions and the availability of cDNA markers for mapping, along with the major advantage of a relatively short life span, make Nothobranchius rachovii an attractive vertebrate genetic model for aging over other available vertebrate models.

  14. A behavioural dynamic model of the relative age effect.

    PubMed

    Pierson, Kawika; Addona, Vittorio; Yates, Philip

    2014-01-01

    The relationship between date of birth and success in a variety of sports, including hockey, is well established. This phenomenon is known as the relative age effect (RAE). We model the RAE in Canadian youth hockey as a positive feedback loop where an initial age advantage is reinforced through additional training and playing opportunities based on perceived skill superiority. The same causal mechanism leads to a higher quit rate for relatively younger players. Our model effectively replicates the birth month distribution of Canadian National Hockey League players (R2 = 86.79%) when driven by Canadian birth distributions. We use this model to evaluate three policies that aim to lessen the RAE. All of the policies reduce the RAE with a significant delay. The most effective policy is a combination of providing additional support to age disadvantaged children and rotating the cut-off date for youth leagues between January 1st and July 1st annually. In equilibrium, this approach leads to a 96% reduction in the RAE compared to the base case.

  15. Zebrafish (Danio rerio) as a model for the study of aging and exercise: physical ability and trainability decrease with age.

    PubMed

    Gilbert, Matthew J H; Zerulla, Tanja C; Tierney, Keith B

    2014-02-01

    A rapidly aging global population has motivated the development and use of models for human aging. Studies on aging have shown parallels between zebrafish and humans at the internal organization level; however, few parallels have been studied at the whole-organism level. Furthermore, the effectiveness of exercise as a method to mitigate the effects of aging has not been studied in zebrafish. We investigated the effects of aging and intermittent exercise on swimming performance, kinematics and behavior. Young, middle-aged and old zebrafish (20-29, 36-48 and 60-71% of average lifespan, respectively) were exercised to exhaustion in endurance and sprint swimming tests once a week for four weeks. Both endurance and sprint performance decreased with increased age. Swimming performance improved with exercise training in young and middle-aged zebrafish, but not in old zebrafish. Tail-beat amplitude, which is akin to stride length in humans, increased for all age groups with training. Zebrafish turning frequency, which is an indicator of routine activity, decreased with age but showed no change with exercise. In sum, our results show that zebrafish exhibit a decline in whole-organism performance and trainability with age. These findings closely resemble the senescence-related declines in physical ability experienced by humans and mammalian aging models and therefore support the use of zebrafish as a model for human exercise and aging.

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

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

    PubMed

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

    2014-01-01

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

  18. Re-Evaluating Neonatal-Age Models for Ungulates: Does Model Choice Affect Survival Estimates?

    PubMed Central

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

    2014-01-01

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

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

    USGS Publications Warehouse

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

    2014-01-01

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

  20. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  1. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

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

    SciTech Connect

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

    2011-05-31

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

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

    PubMed Central

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

    2015-01-01

    The comprehension of spoken language has been characterized by a number of “local” theories that have focused on specific aspects of the task: models of word recognition, models of selective attention, accounts of thematic role assignment at the sentence level, and so forth. The ease of language understanding (ELU) model (Rönnberg et al., 2013) stands as one of the few attempts to offer a fully encompassing framework for language understanding. In this paper we discuss interactions between perceptual, linguistic, and cognitive factors in spoken language understanding. Central to our presentation is an examination of aspects of the ELU model that apply especially to spoken language comprehension in adult aging, where speed of processing, working memory capacity, and hearing acuity are often compromised. We discuss, in relation to the ELU model, conceptions of working memory and its capacity limitations, the use of linguistic context to aid in speech recognition and the importance of inhibitory control, and language comprehension at the sentence level. Throughout this paper we offer a constructive look at the ELU model; where it is strong and where there are gaps to be filled. PMID:26124724

  4. The OMS3 JGrass-NewAge Environmental Modelling System

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    PubMed

    Benjamin, Aaron S

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Stein, Carol A.; Stein, Seth

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

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

    NASA Astrophysics Data System (ADS)

    Gorshkov, Vyacheslav; Privman, Vladimir; Libert, Sergiy

    2016-11-01

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

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

    SciTech Connect

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

    2010-09-01

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

  9. Overview of Modeling and Simulations of Plutonium Aging

    SciTech Connect

    Schwartz, A J; Wolfer, W G

    2007-04-24

    Computer-aided materials research is now an integral part of science and technology. It becomes particularly valuable when comprehensive experimental investigations and materials testing are too costly, hazardous, or of excessive duration; then, theoretical and computational studies can supplement and enhance the information gained from limited experimental data. Such is the case for improving our fundamental understanding of the properties of aging plutonium in the nuclear weapons stockpile. The question of the effects of plutonium aging on the safety, security, and reliability of the nuclear weapons stockpile emerged after the United States closed its plutonium manufacturing facility in 1989 and decided to suspend any further underground testing of nuclear weapons in 1992. To address this, the Department of Energy's National Nuclear Security Administration (NNSA) initiated a research program to investigate plutonium aging, i.e., the changes with time of properties of Pu-Ga alloys employed in the nuclear weapons and to develop models describing these changes sufficiently reliable to forecast them for several decades. The November 26, 2006 press release by the NNSA summarizes the conclusions of the investigation, '...there appear to be no serious or sudden changes occurring, or expected to occur, in plutonium that would affect performance of pits beyond the well-understood, gradual degradation of plutonium materials'. Furthermore, 'These studies show that the degradation of plutonium in our nuclear weapons will not affect warhead reliability for decades', then NNSA Administrator Linton Brooks said. 'It is now clear that although plutonium aging contributes, other factors control the overall life expectancy of nuclear weapons systems'. The origin of plutonium aging is the natural decay of certain plutonium isotopes. Specifically, it is the process of alpha decay in which a plutonium atom spontaneously splits into a 5 MeV alpha particle and an 85keV uranium recoil

  10. Modeling Diverse Pathways to Age Progressive Volcanism in Subduction Zones.

    NASA Astrophysics Data System (ADS)

    Kincaid, C. R.; Szwaja, S.; Sylvia, R. T.; Druken, K. A.

    2015-12-01

    One of the best, and most challenging clues to unraveling mantle circulation patterns in subduction zones comes in the form of age progressive volcanic and geochemical trends. Hard fought geological data from many subduction zones, like Tonga-Lau, the Cascades and Costa-Rica/Nicaragua, reveal striking temporal patterns used in defining mantle flow directions and rates. We summarize results from laboratory subduction models showing a range in circulation and thermal-chemical transport processes. These interaction styles are capable of producing such trends, often reflecting apparent instead of actual mantle velocities. Lab experiments use a glucose working fluid to represent Earth's upper mantle and kinematically driven plates to produce a range in slab sinking and related wedge transport patterns. Kinematic forcing assumes most of the super-adiabatic temperature gradient available to drive major downwellings is in the tabular slabs. Moreover, sinking styles for fully dynamic subduction depend on many complicating factors that are only poorly understood and which can vary widely even for repeated parameter combinations. Kinematic models have the benefit of precise, repeatable control of slab motions and wedge flow responses. Results generated with these techniques show the evolution of near-surface thermal-chemical-rheological heterogeneities leads to age progressive surface expressions in a variety of ways. One set of experiments shows that rollback and back-arc extension combine to produce distinct modes of linear, age progressive melt delivery to the surface through a) erosion of the rheological boundary layer beneath the overriding plate, and deformation and redistribution of both b) mantle residuum produced from decompression melting and c) formerly active, buoyant plumes. Additional experiments consider buoyant diapirs rising in a wedge under the influence of rollback, back-arc spreading and slab-gaps. Strongly deflected diapirs, experiencing variable rise

  11. Modeling age-of-onset: Cox model with latent major gene effects

    SciTech Connect

    Li, H.; Thompson, E.A.

    1994-09-01

    Analysis of age-of-onset is a key factor in the segregation and linkage analysis of complex genetic traits, but is complicated by the censoring of unaffected individuals. Most previous work has used parametric distributional assumptions, but it is hard to characterize the distribution of age-of-onset by a single distribution. Other approaches discretize age-of-onset and use logistic regression to model incidence; this approach does not use the information fully. Frailty models have been used for age-of-oset in the biostatistics literature, but these models do not lend themselves to modeling the correlations due to genetic effects which segregate within a family. Here, we propose use of the Cox model with latent major gene effects; conditional on the major genotypes, Cox`s proportional hazards model is used for age-of-onset for each individual. This is a semiparametric model; we do not specify the baseline hazard function. Likelihood analysis of such models is restricted by the difficulty in evaluating of maximizing the likelihood, especially when data are available for some of the members of an extended pedigree. Markov chain Monte Carlo permits genotypic configurations to be realized from the posterior distributions given a current model and the observed data. Hence methods for likelihood analysis can be developed: Monte Carlo EM is used for estimation of the parameters and their variance-covariance matrix. Markers and observed covariates are easily incorporated into this analysis. We present the model, methods for likelihood analysis and the results of a simulation study. The results are comparable with those based on a Cox model with known genotypic dependence in a pedigree. An early-onset Alzheimer`s pedigree and some breast cancer pedigrees have been used as real data examples. Some possible extensions are also discussed.

  12. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT 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. PMID:26035859

  13. Improved age modelling and high-precision age estimates of late Quaternary tephras, for accurate palaeoclimate reconstruction

    NASA Astrophysics Data System (ADS)

    Blockley, Simon P. E.; Bronk Ramsey, C.; Pyle, D. M.

    2008-10-01

    The role of tephrochronology, as a dating and stratigraphic tool, in precise palaeoclimate and environmental reconstruction, has expanded significantly in recent years. The power of tephrochronology rests on the fact that a tephra layer can stratigraphically link records at the resolution of as little as a few years, and that the most precise age for a particular tephra can be imported into any site where it is found. In order to maximise the potential of tephras for this purpose it is necessary to have the most precise and robustly tested age estimate possible available for key tephras. Given the varying number and quality of dates associated with different tephras it is important to be able to build age models to test competing tephra dates. Recent advances in Bayesian age modelling of dates in sequence have radically extended our ability to build such stratigraphic age models. As an example of the potential here we use Bayesian methods, now widely applied, to examine the dating of some key Late Quaternary tephras from Italy. These are: the Agnano Monte Spina Tephra (AMST), the Neapolitan Yellow Tuff (NYT) and the Agnano Pomici Principali (APP), and all of them have multiple estimates of their true age. Further, we use the Bayesian approaches to generate a revised mixed radiocarbon/varve chronology for the important Lateglacial section of the Lago Grande Monticchio record, as a further illustration of what can be achieved by a Bayesian approach. With all three tephras we were able to produce viable model ages for the tephra, validate the proposed 40Ar/ 39Ar age ranges for these tephras, and provide relatively high precision age models. The results of the Bayesian integration of dating and stratigraphic information, suggest that the current best 95% confidence calendar age estimates for the AMST are 4690-4300 cal BP, the NYT 14320-13900 cal BP, and the APP 12380-12140 cal BP.

  14. Age and structure of a model vapour-deposited glass

    PubMed Central

    Reid, Daniel R.; Lyubimov, Ivan; Ediger, M. D.; de Pablo, Juan J.

    2016-01-01

    Glass films prepared by a process of physical vapour deposition have been shown to have thermodynamic and kinetic stability comparable to those of ordinary glasses aged for thousands of years. A central question in the study of vapour-deposited glasses, particularly in light of new knowledge regarding anisotropy in these materials, is whether the ultra-stable glassy films formed by vapour deposition are ever equivalent to those obtained by liquid cooling. Here we present a computational study of vapour deposition for a two-dimensional glass forming liquid using a methodology, which closely mimics experiment. We find that for the model considered here, structures that arise in vapour-deposited materials are statistically identical to those observed in ordinary glasses, provided the two are compared at the same inherent structure energy. We also find that newly deposited hot molecules produce cascades of hot particles that propagate far into the film, possibly influencing the relaxation of the material. PMID:27762262

  15. Ploidy, sex and crossing over in an evolutionary aging model

    NASA Astrophysics Data System (ADS)

    Lobo, Matheus P.; Onody, Roberto N.

    2006-02-01

    Nowadays, many forms of reproduction coexist in nature: Asexual, sexual, apomictic and meiotic parthenogenesis, hermaphroditism and parasex. The mechanisms of their evolution and what made them successful reproductive alternatives are very challenging and debated questions. Here, using a simple evolutionary aging model, we give a possible scenario. By studying the performance of populations where individuals may have diverse characteristics-different ploidies, sex with or without crossing over, as well as the absence of sex-we find an evolution sequence that may explain why there are actually two major or leading groups: Sexual and asexual. We also investigate the dependence of these characteristics on different conditions of fertility and deleterious mutations. Finally, if the primeval organisms on Earth were, in fact, asexual individuals we conjecture that the sexual form of reproduction could have more easily been set and found its niche during a period of low-intensity mutations.

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

    USGS Publications Warehouse

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

  18. Aging Through Hierarchical Coalescence in the East Model

    NASA Astrophysics Data System (ADS)

    Faggionato, A.; Martinelli, F.; Roberto, C.; Toninelli, C.

    2012-01-01

    We rigorously analyze the low temperature non-equilibrium dynamics of the East model, a special example of a one dimensional oriented kinetically constrained particle model, when the initial distribution is different from the reversible one and for times much smaller than the global relaxation time. This setting has been intensively studied in the physics literature to analyze the slow dynamics which follows a sudden quench from the liquid to the glass phase. In the limit of zero temperature (i.e. a vanishing density of vacancies) and for initial distributions such that the vacancies form a renewal process, we prove that the density of vacancies, the persistence function and the two-time autocorrelation function behave as staircase functions with several plateaux. Furthermore the two-time autocorrelation function displays an aging behavior. We also provide a sharp description of the statistics of the domain length as a function of time, a domain being the interval between two consecutive vacancies. When the initial renewal process has finite mean, our results confirm (and generalize) previous findings of the physicists for the restricted case of a product Bernoulli measure. However we show that a different behavior appears when the initial domain distribution is in the attraction domain of a α-stable law. All the above results actually follow from a more general result which says that the low temperature dynamics of the East model is very well described by that of a certain hierarchical coalescence process, a probabilistic object which can be viewed as a hierarchical sequence of suitably linked coalescence processes and whose asymptotic behavior has been recently studied in Faggionato et al. (Universality in one dimensional hierarchical 1059 coalescence processes. Preprint, 2011).

  19. Modeling of aging in plutonium by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Pochet, P.

    2003-04-01

    The origin of aging in plutonium lies in the extra formation of defects due to self-decay of 239Pu. The modeling of the formation of these defects is achieved by molecular dynamics (MD). In this work a simple EAM potential has been used to study defects formation in fcc plutonium and a 2 keV cascade is analyzed. A large pressure wave is generated around the cascade core. In the used MD code the pressure wave is not absorbed at the box boundaries and due to the periodic boundary conditions, the use of a very large box is crucial in order to avoid interaction of the cascade with itself. More than 800 000 atoms are needed to deal with this small 2 keV cascade without any artifacts. This effect comes from the very low bulk modulus of fcc Pu. The relative long time to achieve the annealing is also connected to the bulk modulus. These results are discussed in terms of large pressure wave: alloying effects are predicted using that viewpoint.

  20. Characterizing cognitive aging in humans with links to animal models

    PubMed Central

    Alexander, Gene E.; Ryan, Lee; Bowers, Dawn; Foster, Thomas C.; Bizon, Jennifer L.; Geldmacher, David S.; Glisky, Elizabeth L.

    2012-01-01

    With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline. PMID:22988439

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

    NASA Astrophysics Data System (ADS)

    Anguelov, R.; Kojouharov, H.

    2009-10-01

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

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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. PMID:26839399

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Urban groundwater age modeling under unconfined condition - Impact of underground structures on groundwater age: Evidence of a piston effect

    NASA Astrophysics Data System (ADS)

    Attard, Guillaume; Rossier, Yvan; Eisenlohr, Laurent

    2016-04-01

    In this paper, underground structures are shown to have a major influence on the groundwater mean age distribution described as a dispersive piston effect. Urban underground development does not occur without impacts on subsoil resources. In particular, groundwater resources can be vulnerable and generate disturbances when this space is exploited. Groundwater age spatial distribution data are fundamental for resource management as it can provide operational sustainability indicators. However, the application of groundwater age modeling is neglected regarding the potential effect of underground structures in urban areas. A three dimensional modeling approach was conducted to quantify the impact of two underground structures: (1) an impervious structure and (2) a draining structure. Both structures are shown to cause significant mixing processes occurring between shallow and deeper aquifers. The design technique used for draining structures is shown to have the greatest impact, generating a decrease in mean age of more than 80% under the structure. Groundwater age modeling is shown to be relevant for highlighting the role played by underground structures in advective-dispersive flows in urban areas.

  6. Radiocarbon age modeling: dissolution, bioturbation and sediment redistribution

    NASA Astrophysics Data System (ADS)

    Mekik, F.

    2012-12-01

    We generated radiocarbon dates for whole and fragmented planktonic foraminifer tests (by several species) from a series of core tops which have experienced little dissolution from two depth transects (Rio Grande Rise - RIO and Ontong Java Plateau - OJP) and from down core records from three tropical Pacific cores with significantly different sediment accumulation rates. We also generated new radiocarbon data from both whole Globorotalia menardii shells and its fragments within the same sediments in order to test the robustness of a calcite dissolution proxy, the G. menardii Fragmentation Index (MFI). Our data reveal that the ages of all sediment components increase with increasing dissolution. This is most easily observable on RIO where the age offset between the shallowest samples and deepest samples is ~5 ka, while the mixing ages of the cores are ~1.9ka. This result is new and significant because previous work has always been in the tropical Pacific where bioturbation and mixing ages are high. Furthermore, two of the 7 core top samples from RIO revealed whole G. menardii shells of Glacial age. This is surprising because G. menardiis have not been reported in sediments from the Atlantic Ocean older than 13,000 years. Lastly, we found that the higher the sediment accumulation rate, the closer the age offset between G. menradii whole shells and its fragments in the same sediments both on RIO and OJP. This is important for the interpretation of down core work with MFI.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Michael, R; Bron, A J

    2011-04-27

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

  9. Autophagy drives epidermal deterioration in a Drosophila model of tissue aging.

    PubMed

    Scherfer, Christoph; Han, Violet C; Wang, Yan; Anderson, Aimee E; Galko, Michael J

    2013-04-01

    Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific aging remains an open question. To examine the crosstalk between longevity programs and specific tissues during aging, biomarkers of organ-specific aging are urgently needed. Since the earliest signs of aging occur in the skin, we sought to examine skin aging in a genetically tractable model. Here we introduce a Drosophila model of skin aging. The epidermis undergoes a dramatic morphological deterioration with age that includes membrane and nuclear loss. These changes were decelerated in a long-lived mutant and accelerated in a short-lived mutant. An increase in autophagy markers correlated with epidermal aging. Finally, the epidermis of Atg7 mutants retained younger characteristics, suggesting that autophagy is a critical driver of epidermal aging. This is surprising given that autophagy is generally viewed as protective during aging. Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity. Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging.

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

    PubMed

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

    2015-01-01

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

  11. NMR and molecular modeling: application to wine ageing

    NASA Astrophysics Data System (ADS)

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

    1998-02-01

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

  12. An Age-Graded Model for Career Development Education

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    1974-01-01

    This paper attempts to provide a framework by which educators interested in stimulating career development can choose the learning experiences most likely to have payoffs for different age youth. Eight stages of child development are described with career development themes suggested for each stage along with sample activities. (Author)

  13. Aging and Predicting Inferences: A Diffusion Model Analysis

    ERIC Educational Resources Information Center

    McKoon, Gail; Ratcliff, Roger

    2013-01-01

    In the domain of discourse processing, it has been claimed that older adults (60-0-year-olds) are less likely to encode and remember some kinds of information from texts than young adults. The experiment described here shows that they do make a particular kind of inference to the same extent that college-age adults do. The inferences examined were…

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

    PubMed Central

    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. PMID:28199320

  15. Rb-Sr age of a Luna 16 basalt and the model age of lunar soils.

    NASA Technical Reports Server (NTRS)

    Papanastassiou, D. A.; Wasserburg, G. J.

    1972-01-01

    An internal isochron was determined on a small basalt fragment (sample B-1) returned from the Luna 16 mission, which yields an age of 3.42 plus or minus 0.8 b.y. and a low initial Sr87/Sr86 value. A comparison is made of the data from four lunar missions to mare sites which shows that the last period of major flooding of the mare basins is confined to a narrow time interval of only 0.55 b.y. The direct evidence of major lunar magmatic activity appears to be confined to the interval from 3.1 to 4.0 b.y. The Sr87/Sr86 values for all mare basalts are extremely primitive and lie in a rather narrow range. A diagram is given for initial Sr87/Sr86 as a function of time for all lunar rocks.

  16. Modeling the Information Age Combat Model: An Agent-Based Simulation of Network Centric Operations

    NASA Technical Reports Server (NTRS)

    Deller, Sean; Rabadi, Ghaith A.; Bell, Michael I.; Bowling, Shannon R.; Tolk, Andreas

    2010-01-01

    The Information Age Combat Model (IACM) was introduced by Cares in 2005 to contribute to the development of an understanding of the influence of connectivity on force effectiveness that can eventually lead to quantitative prediction and guidelines for design and employment. The structure of the IACM makes it clear that the Perron-Frobenius Eigenvalue is a quantifiable metric with which to measure the organization of a networked force. The results of recent experiments presented in Deller, et aI., (2009) indicate that the value of the Perron-Frobenius Eigenvalue is a significant measurement of the performance of an Information Age combat force. This was accomplished through the innovative use of an agent-based simulation to model the IACM and represents an initial contribution towards a new generation of combat models that are net-centric instead of using the current platform-centric approach. This paper describes the intent, challenges, design, and initial results of this agent-based simulation model.

  17. All age-depth models are wrong, but are getting better

    NASA Astrophysics Data System (ADS)

    Trachsel, Mathias; Chipperfield, Joseph D.; Telford, Richard J.

    2015-04-01

    Construction of accurate age-depth relationships and realistic assessment of their uncertainties is one of the fundamental prerequisites for comparing and correlating Late Quaternary stratigraphic proxy records. Four widely used age-depth modelling routines: i) clam, ii) OxCal, iii) Bacon, and iv) Bchron were tested using radiocarbon dates simulated from varved sediment stratigraphies. All methods produced average age-depth models that were close to the true varve age, but the uncertainty estimation differed considerably among models. Age uncertainties were underestimated by clam, whereas age uncertainties produced by Bchron were too large. Using OxCal and Bacon, setting of model specific parameters influenced the estimated uncertainties, which varied from too large to too small. Still, compared to the study by Telford et al. (2004), the use of Bayesian age-depth models greatly improved on the assessment of uncertainties of age-depth models. Reference: Telford et al. (2004), All age-depth models are wrong: but how badly? Quaternary Science Reviews, 23,1-5.

  18. Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

    PubMed

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

    2014-10-01

    Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining. A multidisciplinary cross-sector team from disciplines of public health, sociology, gerontology and nursing developed four competency-based courses that focus on healthy aging, behavior change strategies, program management, an internship, and an option for leader training in the Chronic Disease Self-Management Program. To enhance implementation and fidelity, intensive faculty development training was provided to all instructors and community agency partners. Baseline and postprogram evaluation of competencies for faculty and students was conducted. Process evaluation for both groups focused on satisfaction with the curricula and suggestions for program improvement. SHARP has been piloted five times at two community colleges. Trainees (n = 113) were primarily community college students (n = 108) and current aging service personnel (n = 5). Statistically significant improvements in all competencies were found for both faculty and students. Process evaluation outcomes identified the needed logical and component adaptations to enhance the feasibility of program implementation, dissemination, and student satisfaction. The SHARP program provides a well-tested, evidence-based effective model for addressing workforce preparation in support of healthy aging service program expansion and delivery.

  19. Budding yeast as a model organism to study the effects of age.

    PubMed

    Denoth Lippuner, Annina; Julou, Thomas; Barral, Yves

    2014-03-01

    Although a budding yeast culture can be propagated eternally, individual yeast cells age and eventually die. The detailed knowledge of this unicellular eukaryotic species as well as the powerful tools developed to study its physiology makes budding yeast an ideal model organism to study the mechanisms involved in aging. Considering both detrimental and positive aspects of age, we review changes occurring during aging both at the whole-cell level and at the intracellular level. The possible mechanisms allowing old cells to produce rejuvenated progeny are described in terms of accumulation and inheritance of aging factors. Based on the dynamic changes associated with age, we distinguish different stages of age: early age, during which changes do not impair cell growth; intermediate age, during which aging factors start to accumulate; and late age, which corresponds to the last divisions before death. For each aging factor, we examine its asymmetric segregation and whether it plays a causal role in aging. Using the example of caloric restriction, we describe how the aging process can be modulated at different levels and how changes in different organelles might interplay with each other. Finally, we discuss the beneficial aspects that might be associated with age.

  20. 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

    PubMed Central

    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. PMID:25538730

  1. The development of a ductility-based aging model for low temperature aged U-6Nb alloy

    SciTech Connect

    Bridges, B

    2005-03-24

    This study focuses on the ductility evaluation of low-temperature (100 and 200 C) aged U-6Nb alloy. The objective is to develop a ductility-based aging model to improve lifetime prediction for weapon components in the stockpile environment. Literature review shows that the work hardening n-value and the strain-rate hardening mvalue are the two most important metallurgical factors for the uniform and the post-uniform (necking) ductility control, respectively. Unfortunately, both n and m values of the U-6Nb alloy are lacking. The study shows that the total ductility of U-6Nb is dominated by the uniform ductility, which deteriorates in both 100 C and 200 C aging. Further analysis shows that the uniform ductility correlates well with the work hardening n-value of the later stage deformation in which dislocation-slip is the mechanism. The kinetics of the loss of uniform ductility and the associated reduction in work-hardening n-value in low temperature aging will be used for the development of a ductility-based aging model. The necking ductility appears to be a minor but significant factor in the total ductility of U-6Nb. It does not show a clear trend due to large data scatter. The uncertain nature of necking failure may always hinder a reliable measurement of necking ductility. Consequently, a precise measurement of strain-rate hardening m-value could be a viable alternative to model the metallurgical contribution to the necking ductility. The conventional strain rate step-change method and the ABI (Automated-Ball-Indentation) test both show promising result in m-value measurement.

  2. Aging and strain softening model for episodic faulting

    USGS Publications Warehouse

    Stuart, W.D.

    1979-01-01

    Episodic slip on shallow crustal faults can be qualitatively explained by postulating a fault constitutive law that is the superposition of two limiting material responses: (1) strain softening after peak stress during large strain rates, and (2) strength (peak stress) recovery during aging at small strain rates. A single law permits a variety of seismic and aseismic phenomena to occur over a range of space and time scales. Specific cases are determined by the spatial variation of material constants, recent deformation history, crustal rigidity, and remote forcing. ?? 1979.

  3. The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

    PubMed

    Harel, Itamar; Brunet, Anne

    2015-01-01

    Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases.

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

    PubMed Central

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

    2015-01-01

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

  5. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

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

    NASA Astrophysics Data System (ADS)

    Rizzuto, Aaron C.; Ireland, Michael J.; Dupuy, Trent J.; Kraus, Adam L.

    2016-02-01

    We present the results of a long-term orbit monitoring program, using sparse aperture masking observations taken with NIRC2 on the Keck-II telescope, of seven G- to M-type members of the Upper Scorpius subgroup of the Sco-Cen OB association. We present astrometry and derived orbital elements of the binary systems we have monitored, and also determine the age, component masses, distance, and reddening for each system using the orbital solutions and multi-band photometry, including Hubble Space Telescope photometry, and a Bayesian fitting procedure. We find that the models can be forced into agreement with any individual system by assuming an age, but that age is not consistent across the mass range of our sample. The G-type binary systems in our sample have model ages of ˜11.5 Myr, which is consistent with the latest age estimates for Upper Scorpius, while the M-type binary systems have significantly younger model ages of ˜7 Myr. Based on our fits, this age discrepancy in the models corresponds to a luminosity underprediction of 0.8-0.15 dex, or equivalently an effective temperature overprediction of 100-300 K for M-type stars at a given pre-main-sequence age. We also find that the M-type binary system RXJ 1550.0-2312 has an age (˜16 Myr) and distance (˜85 pc) consistent with membership in the Upper Centaurus Lupus subgroup.

  7. Mathematical Model of Three Age-Structured Transmission Dynamics of Chikungunya Virus

    PubMed Central

    Agusto, Folashade B.; Easley, Shamise; Freeman, Kenneth; Thomas, Madison

    2016-01-01

    We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population. PMID:27190548

  8. Aging and symptoms of anxiety and depression: structural invariance of the tripartite model.

    PubMed

    Teachman, Bethany A; Siedlecki, Karen L; Magee, Joshua C

    2007-03-01

    Negative affect measures were evaluated in a cross-sectional community sample of adults aged 18-93 (N = 335) to examine the structure of neuroticism, anxiety, and depressive symptoms in young, middle, and older adult cohorts. Structural equation modeling was used to contrast 3 nested models: a 1-factor general distress model; a 2-factor high negative-low positive affect model; and a 3-factor "tripartite model" reflecting a higher order Negative Affect factor that is common to depression and anxiety problems and 2 lower order factors, Low Positive Affect (mostly specific to depression) and Arousal (specific to anxiety/panic). As expected, the tripartite model fit best for all age groups. Further, multigroup analyses indicated age invariance for the tripartite model, suggesting the model can be effectively applied with older populations.

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2012-04-01

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

  11. Applicability of Willems model for dental age estimations in Brazilian children.

    PubMed

    Franco, Ademir; Thevissen, Patrick; Fieuws, Steffen; Souza, Paulo Henrique Couto; Willems, Guy

    2013-09-10

    Several studies described tooth development as a reliable pathway for age estimations. Depending on the considered life span, the dental age indicators vary. In children, combinations of developing teeth provide the best information about age. In sub adults third molar mineralization is almost exclusively considered. The aim of this study was, firstly, to verify the Willems model in a Brazilian sample. Secondly, to observe differences between the Willems model and a new developed Brazilian model. Thirdly, the information of permanent teeth (PM) and third molar (TM), development was combined for age estimation in children. A sample of 1357 panoramic radiographs of Brazilian males (M) and females (F), with age between 5 and 23 years was collected. The technique of Gleiser and Hunt modified by Kohler (1955) [34] was applied for third molar staging in the entire sample. The Demirjian staging technique was used on the mandibular left permanent teeth (except third molars) of all individuals from 5 to 15 years. Kappa and weighted Kappa statistics were performed to verify inter- and intra-observer reliabilities. Based on the obtained Demirjian scores the Willems model was verified. Next the data were split to develop a new Brazilian model based on the Willems method and to verify the established model. The accuracy in age prediction between the Willems model and the new Brazilian model was compared. Additionally, regression models including PM, TM and PM plus TM information were compared. The Kappa and weighted Kappa statistics revealed high agreement between observers (0.88 Kappa; 0.93 weighted Kappa). The differences between predicted and chronological age for the verified Willems model were expressed in mean errors of -0.17 and -0.38 year for F and M respectively. The differences in mean error between the new developed Brazilian model and the Willems model were 0.02 (F) and 0.20 (M) year. The regression models combining PT and TM information provided only in the age

  12. Modeling Age-Related Differences in Immediate Memory Using SIMPLE

    ERIC Educational Resources Information Center

    Surprenant, Aimee M.; Neath, Ian; Brown, Gordon D. A.

    2006-01-01

    In the SIMPLE model (Scale Invariant Memory and Perceptual Learning), performance on memory tasks is determined by the locations of items in multidimensional space, and better performance is associated with having fewer close neighbors. Unlike most previous simulations with SIMPLE, the ones reported here used measured, rather than assumed,…

  13. In vivo animal models of body composition in aging

    SciTech Connect

    Yasumura, S. |; Jones, K.; Spanne, P.; Schidlovsky, G.; Wielopolski, L.; Ren, X.; Glaros, D.; Xatzikonstantinou, Y. |

    1992-12-31

    We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous {sup 40}K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN Increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCA and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass.

  14. Conscientiousness, health, and aging: the life course of personality model.

    PubMed

    Shanahan, Michael J; Hill, Patrick L; Roberts, Brent W; Eccles, Jacquelynne; Friedman, Howard S

    2014-05-01

    The Conscientiousness (C) of the self and significant others influences health by way of mediational chains involving socioeconomic attainment, the avoidance and neutralization of stressors, the promotion of health behaviors and the minimization of risk behaviors, and the management of symptoms and diseases. Yet, meta-analyses reveal that these associations are moderated by factors that are not well understood. We propose the Life Course of Personality Model (LCP Model), which comprises a series of hypotheses that suggest how such mediational chains are subject to 2 sources of contingency. First, the mechanisms by which C translates into health and the avoidance of risk change from early childhood to late adulthood, involving processes that are specific to phases of the life course; also, however, C influences health by way of continuous processes extending over many decades of life. Second, C may be more consequential in some social contexts than in others, and when accompanied by some constellations of personality characteristics than by others. That is, the mediational processes by which C translates into health and the avoidance of disease are likely moderated by timing, social context (including the C of others), and other aspects of the individual's personality. We consider methodological implications of the LCP Model.

  15. Aging and linear response in the Hébraud–Lequeux model for amorphous rheology

    NASA Astrophysics Data System (ADS)

    Sollich, Peter; Olivier, Julien; Bresch, Didier

    2017-04-01

    We analyse the aging dynamics of the Hébraud–Lequeux model, a self-consistent stochastic model for the evolution of local stress in an amorphous material. We show that the model exhibits initial-condition dependent freezing: the stress diffusion constant decays with time as D∼ 1/{{t}2} during aging so that the cumulative amount of memory that can be erased, which is given by the time integral of D(t), is finite. Accordingly the shear stress relaxation function, which we determine in the long-time regime, only decays to a plateau and becomes progressively elastic as the system ages. The frequency-dependent shear modulus exhibits a corresponding overall decay of the dissipative part with system age, while the characteristic relaxation times scale linearly with age as expected.

  16. A Comparison of the Age-Spectra from Data Assimilation Models

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark R.; Douglass, Anne R.; Zhu, Zheng-Xin; Pawson, Steven; Einaudi, Franco (Technical Monitor)

    2002-01-01

    We use kinematic and diabatic back trajectory calculations, driven by winds from a general circulation model (GCM) and two different data assimilation systems (DAS), to compute the age spectrum at three latitudes in the lower stratosphere. The age-spectra are compared to chemical transport model (CTM) calculations, and the mean ages from all of these studies are compared to observations. The age spectra computed using the GCM winds show a reasonably well-isolated tropics in good agreement with observations; however, the age spectra determined from the DAS differ from the GCM spectra. For the diabatic trajectory calculations, the age spectrum is too broad as a result of too much exchange between the tropics and mid-latitudes. The age spectrum determined using the kinematic trajectory calculation is less broad and lacks an age offset; both of these features are due to excessive vertical dispersion of parcels. The tropical and mid-latitude mean age difference between the diabatically and kinematically determined age-spectra is about one year, the former being older. The CTM calculation of the age spectrum using the DAS winds shows the same dispersive characteristics of the kinematic trajectory calculation. These results suggest that the current DAS products will not give realistic trace gas distributions for long integrations; they also help explain why the mean ages determined in a number of previous DAS driven CTM's are too young compared with observations. Finally, we note trajectory-generated age spectra show significant age anomalies correlated with the seasonal cycles, and these anomalies can be linked to year-to-year variations in the tropical heating rate. These anomalies are suppressed in the CTM spectra suggesting that the CTM transport is too diffusive.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  18. Comparative and alternative approaches and novel animal models for aging research

    PubMed Central

    Kristan, D. M.

    2008-01-01

    This special issue of AGE showcases powerful alternative or unconventional approaches to basic aging research, including the use of exceptionally long-lived animal model species and comparative methods from evolutionary biology. In this opening paper, we introduce several of these alternative aging research themes, including the comparative phylogenetic approach. This approach applies modern inferential methods for dissecting basic physiological and biochemical mechanisms correlated with phenotypic traits including longevity, slow aging, sustained somatic maintenance, and repair of molecular damage. Comparative methods can be used to assess the general relevance of specific aging mechanisms—including oxidative processes—to diverse animal species, as well as to assess their potential clinical relevance to humans and other mammals. We also introduce several other novel, underexploited approaches with particular relevance to biogerontology, including the use of model animal species or strains that retain natural genetic heterogeneity, studies of effects of infectious disease and parasites on aging and responses to caloric restriction, studies of reproductive aging, and naturally occurring sex differences in aging. We emphasize the importance of drawing inferences from aging phenomena in laboratory studies that can be applied to clinically relevant aging syndromes in long-lived, outbred animals, including humans. PMID:19424857

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    Melnik, Andrey V; Korobeinikov, Andrei

    2013-04-01

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

  2. The Aging and Elderly Population with Mental Retardation: A Model Project in Rural Kentucky.

    ERIC Educational Resources Information Center

    Stone, James A.

    A model to serve rural (Kentucky) mentally retarded adults age 50 and over incorporates generic community resources such as residential, nutritional, medical, recreational, and transportation services with age appropriate activities and programs. The system is intended to provide an alternative to the life-long work setting of the workshop or work…

  3. Age Differences within Secular IQ Trends: An Individual Growth Modeling Approach

    ERIC Educational Resources Information Center

    Kanaya, Tomoe; Ceci, Stephen J.; Scullin, Matthew H.

    2005-01-01

    Age differences within the yo-yo trend in IQ, caused when aging norms that produce inflated scores are replaced with new norms, were examined using longitudinal WISC, WISC-R and WISC-III records of students tested for special education services from 10 school districts. Descriptive and individual growth modeling analyses revealed that while the…

  4. Establishment of a model of acetaminophen-induced hepatotoxicity in different weekly-aged ICR mice.

    PubMed

    Taguchi, K; Tokuno, M; Yamasaki, K; Kadowaki, D; Seo, H; Otagiri, M

    2015-10-01

    Acetaminophen (APAP), a widely used analgesic and antipyretic drug, has the potential to cause lethal hepatotoxicity. Mice are widely used for developing murine models of APAP-induced hepatotoxicity, and many researchers have used these models for APAP-related studies including the fields of biology, pharmacology and toxicology. Although drug-induced hepatotoxicity is dependent on a number of factors (species, gender and age), very few studies have investigated the effect of aging on APAP hepatotoxicity. In this study, we evaluated the effect of age on APAP-induced hepatotoxicity in different weekly-aged mice to establish a model of APAP-induced hepatotoxicity that is an accurate reflection of general experimental conditions. Male ICR mice 4, 6, 8, 10 and 12 weeks old were given APAP intraperitoneally, and mortality, hepatic damage and the plasma concentration of APAP metabolites were evaluated. It was found that younger male ICR mice were relatively resistant to hepatotoxicity induced by intraperitoneal APAP administration. In addition, the APAP-glucuronide concentration in plasma remained essentially the same among the differently-aged mice, while APAP-sulfate levels were dramatically decreased in an age-dependent manner. Thus, it is recommended that mice of the same ages be used in studies related to APAP-induced hepatotoxixity. These results provide evidence in support of not only the age-related changes in susceptibility to APAP-derived hepatotoxicity in mice but also in developing mouse models for APAP-related studies.

  5. A Diffusion Model Analysis of the Effects of Aging on Recognition Memory

    ERIC Educational Resources Information Center

    Ratcliff, Roger; Thapar, Anjali; McKoon, Gail

    2004-01-01

    The effects of aging on response time were examined in a recognition memory experiment with young, college age subjects and older, 60-75 year old subjects. The older subjects were slower than the young subjects but almost as accurate. Ratcliff's (1978) diffusion model was fit to the data and it provided a good account of response times, their…

  6. Degeneration of the Y chromosome in evolutionary aging models

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  7. Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

    PubMed Central

    DeGraff, Deborah S.; Wong, Rebeca

    2014-01-01

    This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

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

    PubMed Central

    2012-01-01

    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. PMID:23281647

  9. A novel strategy for forensic age prediction by DNA methylation and support vector regression model

    PubMed Central

    Xu, Cheng; Qu, Hongzhu; Wang, Guangyu; Xie, Bingbing; Shi, Yi; Yang, Yaran; Zhao, Zhao; Hu, Lan; Fang, Xiangdong; Yan, Jiangwei; Feng, Lei

    2015-01-01

    High deviations resulting from prediction model, gender and population difference have limited age estimation application of DNA methylation markers. Here we identified 2,957 novel age-associated DNA methylation sites (P < 0.01 and R2 > 0.5) in blood of eight pairs of Chinese Han female monozygotic twins. Among them, nine novel sites (false discovery rate < 0.01), along with three other reported sites, were further validated in 49 unrelated female volunteers with ages of 20–80 years by Sequenom Massarray. A total of 95 CpGs were covered in the PCR products and 11 of them were built the age prediction models. After comparing four different models including, multivariate linear regression, multivariate nonlinear regression, back propagation neural network and support vector regression, SVR was identified as the most robust model with the least mean absolute deviation from real chronological age (2.8 years) and an average accuracy of 4.7 years predicted by only six loci from the 11 loci, as well as an less cross-validated error compared with linear regression model. Our novel strategy provides an accurate measurement that is highly useful in estimating the individual age in forensic practice as well as in tracking the aging process in other related applications. PMID:26635134

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

    PubMed

    Roede, James R; Uppal, Karan; Liang, Yongliang; Promislow, Daniel E L; Wachtman, Lynn M; Jones, Dean P

    2013-01-01

    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 (E hCySS) 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 (E h) 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.

  11. Aging and immortality in a cell proliferation model.

    PubMed

    Antal, T; Blagoev, K B; Trugman, S A; Redner, S

    2007-10-07

    We investigate a model of cell division in which the length of telomeres within a cell regulates its proliferative potential. At each division, telomeres undergo a systematic length decrease as well as a superimposed fluctuation due to exchange of telomere DNA between the two daughter cells. A cell becomes senescent when one or more of its telomeres become shorter than a critical length. We map this telomere dynamics onto a biased branching-diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. Using first-passage ideas, we find a phase transition between finite lifetime and immortality (infinite proliferation) of the cell population as a function of the influence of telomere shortening, fluctuations, and cell division.

  12. Systems integrity in health and aging - an animal model approach

    PubMed Central

    2013-01-01

    Human lifespan is positively correlated with childhood intelligence, as measured by psychometric (IQ) tests. The strength of this correlation is similar to the negative effect that smoking has on the life course. This result suggests that people who perform well on psychometric tests in childhood may remain healthier and live longer. The correlation, however, is debated: is it caused exclusively by social-environmental factors or could it also have a biological component? Biological traits of systems integrity that might result in correlations between brain function and lifespan have been suggested but are not well-established, and it is questioned what useful knowledge can come from understanding such mechanisms. In a recent study, we found a positive correlation between brain function and longevity in honey bees. Honey bees are highly social, but relevant social-environmental factors that contribute to cognition-survival correlations in humans are largely absent from insect colonies. Our results, therefore, suggest a biological explanation for the correlation in the bee. Here, we argue that individual differences in stress handling (coping) mechanisms, which both affect the bees’ performance in tests of brain function and their survival could be a trait of systems integrity. Individual differences in coping are much studied in vertebrates, and several species provide attractive models. Here, we discuss how pigs are an interesting model for studying behavioural, physiological and molecular mechanisms that are recruited during stress and that can drive correlations between health, cognition and longevity traits. By revealing biological factors that make individuals susceptible to stress, it might be possible to alleviate health and longevity disparities in people. PMID:24472488

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

    PubMed

    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.

  14. Age-dependent cognitive impairment in a Drosophila Fragile X model and its pharmacological rescue

    PubMed Central

    Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.

    2010-01-01

    Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205

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

    PubMed Central

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

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. PMID:27095931

  16. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M.; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B.; Schlesewsky, Matthias

    2015-01-01

    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

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

    PubMed

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

    2011-04-15

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

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

    PubMed

    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.

  19. The use of genetically engineered model systems for research on human aging.

    PubMed

    Lepperdinger, Guenter; Berger, Peter; Breitenbach, Michael; Frohlich, Kai-Uwe; Grillari, Johannes; Grubeck-Loebenstein, Beatrix; Madeo, Frank; Minois, Nadege; Zwerschke, Werner; Jansen-Durr, Pidder

    2008-05-01

    A major goal in the field of aging research is to identify molecular mechanisms of aging at the cellular level, which are anticipated to form the basis for the development of age-associated dysfunctions and diseases in human beings. Recent progress in research into model organisms of aging has allowed determining precise molecular mechanisms and genetic determinants of the aging process, which appear to be conserved in evolution and some of which apply to human aging as well. The consortium of the authors focuses on aging mechanisms at the cellular level, and exploits the potential of genetic analyses in lower eukaryotic model organisms for a better understanding of regulatory pathways implicated in aging processes. We have established a new database (GiSAO), which provides a unique resource for the analysis of genome-wide expression patterns as being regulated by senescence, apoptosis and oxidative stress in our model systems. This has led to the identification of candidate genes, which are being tested for their impact on lifespan regulation in yeast, the fruit fly Drosophila melanogaster and the nematode C. elegans.

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

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-05-28

    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.

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

    PubMed

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

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P < .05). Also, GP treatment prevented age-induced anxiety-like behavior in AG-GP rats (P < .05). Neither short-term nor long-term age-associated memory deficits improved with GP treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P < .05), whereas protein carbonylation was recovered in the amygdala region only (P < .05). Grape powder by regulating oxidative stress ameliorates age-induced anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  2. Characterizing cognitive aging of spatial and contextual memory in animal models

    PubMed Central

    Foster, Thomas C.; DeFazio, R. A.; Bizon, Jennifer L.

    2012-01-01

    Episodic memory, especially memory for contextual or spatial information, is particularly vulnerable to age-related decline in humans and animal models of aging. The continuing improvement of virtual environment technology for testing humans signifies that widely used procedures employed in the animal literature for examining spatial memory could be developed for examining age-related cognitive decline in humans. The current review examines cross species considerations for implementing these tasks and translating findings across different levels of analysis. The specificity of brain systems as well as gaps in linking human and animal laboratory models is discussed. PMID:22988436

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

    SciTech Connect

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

    2007-01-01

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

  4. A dimensional liability model of age differences in mental disorder prevalence: evidence from a national sample.

    PubMed

    Hoertel, Nicolas; McMahon, Kibby; Olfson, Mark; Wall, Melanie M; Rodríguez-Fernández, Jorge Mario; Lemogne, Cédric; Limosin, Frédéric; Blanco, Carlos

    2015-05-01

    Recent theories have proposed a metastructure that organizes related mental disorders into broad dimensions of psychopathology (i.e., internalizing and externalizing dimensions). Prevalence rates of most mental disorders, when examined independently, are substantially lower in older than in younger adults, which may affect this metastructure. Within a nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093), we developed a dimensional liability model of common psychiatric disorders to clarify whether aging affects specific disorders or general dimensions of psychopathology. Significant age differences existed across age groups (18-24, 25-34, 35-44, 45-54, 55-64, 65-75 and 75+), such that older adults showed lower prevalence rates of most disorders compared to younger adults. We next investigated patterns of disorder comorbidity for past-year psychiatric disorders and found that a distress-fear-externalizing liability model fit the data well. This model was age-group invariant and indicated that the observed lower prevalence of mental disorders with advancing age originates from lower average means on externalizing and internalizing liability dimensions. This unifying dimensional liability model of age and mental disorder comorbidity can help inform the role of aging on mental disorder prevalence for research and intervention efforts, and service planning for the impending crisis in geriatric mental health.

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

    PubMed

    Levy, Sheri R

    2016-08-10

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

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

    PubMed

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

    2011-12-01

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

  7. Predicting age-related differences in visual information processing using a two-stage queuing model.

    PubMed

    Ellis, R D; Goldberg, J H; Detweiler, M C

    1996-05-01

    Recent work on age-related differences in some types of visual information processing has qualitatively stated that younger adults are able to develop parallel processing capability, while older adults remain serial processors. A mathematical model based on queuing theory was used to quantitatively predict and parameterize age-related differences in the perceptual encoding and central decision-making aspects of a multiple-frame search task. Statistical results indicated main effects for frame duration, display load, age group, and session of practice. Comparison of the full model and a restricted model indicated an efficient contribution of the encoding speed parameter. The best-fitting parameter set indicated that (1) younger participants processed task information with a two-channel parallel system, while older participants were serial processors; and (2) perceptual encoding had a large impact on age-related differences in task performance. Results are discussed with implications for human factors design principles.

  8. Accelerated failure time models provide a useful statistical framework for aging research.

    PubMed

    Swindell, William R

    2009-03-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

  9. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Romo-Madero, Sonia; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Rodríguez-Gómez, José A; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2016-01-01

    Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches.

  10. COMPONENT DEGRADATION SUSCEPTIBILITIES AS THE BASES FOR MODELING REACTOR AGING RISK

    SciTech Connect

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

    2010-07-18

    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.

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

    PubMed Central

    Djordjevic, Ivan B.

    2015-01-01

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

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

    PubMed

    Djordjevic, Ivan B

    2015-08-24

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

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

    PubMed

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

    2016-02-01

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

  14. Using remotely-sensed multispectral imagery to build age models for alluvial fan surfaces

    NASA Astrophysics Data System (ADS)

    D'Arcy, Mitch; Mason, Philippa J.; Roda Boluda, Duna C.; Whittaker, Alexander C.; Lewis, James

    2016-04-01

    Accurate exposure age models are essential for much geomorphological field research, and generally depend on laboratory analyses such as radiocarbon, cosmogenic nuclide, or luminescence techniques. These approaches continue to revolutionise geomorphology, however they cannot be deployed remotely or in situ in the field. Therefore other methods are still needed for producing preliminary age models, performing relative dating of surfaces, or selecting sampling sites for the laboratory analyses above. With the widespread availability of detailed multispectral imagery, a promising approach is to use remotely-sensed data to discriminate surfaces with different ages. Here, we use new Landsat 8 Operational Land Imager (OLI) multispectral imagery to characterise the reflectance of 35 alluvial fan surfaces in the semi-arid Owens Valley, California. Alluvial fans are useful landforms to date, as they are widely used to study the effects of tectonics, climate and sediment transport processes on source-to-sink sedimentation. Our target fan surfaces have all been mapped in detail in the field, and have well-constrained exposure ages ranging from modern to ~ 125 ka measured using a high density of 10Be cosmogenic nuclide samples. Despite all having similar granitic compositions, the spectral properties of these surfaces vary systematically with their exposure ages. Older surfaces demonstrate a predictable shift in reflectance across the visible and short-wave infrared spectrum. Simple calculations, such as the brightness ratios of different wavelengths, generate sensitive power law relationships with exposure age that depend on post-depositional alteration processes affecting these surfaces. We investigate what these processes might be in this dryland location, and evaluate the potential for using remotely-sensed multispectral imagery for developing surface age models. The ability to remotely sense relative exposure ages has useful implications for preliminary mapping, selecting

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

    PubMed

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

    2014-01-01

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

  16. Modeling age-specific cancer incidences using logistic growth equations: implications for data collection.

    PubMed

    Shen, Xing-Rong; Feng, Rui; Chai, Jing; Cheng, Jing; Wang, De-Bin

    2014-01-01

    Large scale secular registry or surveillance systems have been accumulating vast data that allow mathematical modeling of cancer incidence and mortality rates. Most contemporary models in this regard use time series and APC (age-period-cohort) methods and focus primarily on predicting or analyzing cancer epidemiology with little attention being paid to implications for designing cancer registry, surveillance or evaluation initiatives. This research models age-specific cancer incidence rates using logistic growth equations and explores their performance under different scenarios of data completeness in the hope of deriving clues for reshaping relevant data collection. The study used China Cancer Registry Report 2012 as the data source. It employed 3-parameter logistic growth equations and modeled the age-specific incidence rates of all and the top 10 cancers presented in the registry report. The study performed 3 types of modeling, namely full age-span by fitting, multiple 5-year- segment fitting and single-segment fitting. Measurement of model performance adopted adjusted goodness of fit that combines sum of squred residuals and relative errors. Both model simulation and performance evalation utilized self-developed algorithms programed using C# languade and MS Visual Studio 2008. For models built upon full age-span data, predicted age-specific cancer incidence rates fitted very well with observed values for most (except cervical and breast) cancers with estimated goodness of fit (Rs) being over 0.96. When a given cancer is concerned, the R valuae of the logistic growth model derived using observed data from urban residents was greater than or at least equal to that of the same model built on data from rural people. For models based on multiple-5-year-segment data, the Rs remained fairly high (over 0.89) until 3-fourths of the data segments were excluded. For models using a fixed length single-segment of observed data, the older the age covered by the corresponding

  17. Mechanism of Origin of Conduction Disturbances in Aging Human Atrial Bundles: Experimental and Model Study

    PubMed Central

    Spach, Madison S.; Heidlage, J. Francis; Dolber, Paul C.; Barr, Roger C.

    2007-01-01

    BACKGROUND Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site prior to a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue has remained unknown. OBJECTIVE This study was to determine if the pattern of cellular connectivity in aging human atrial bundles produces a mechanism for variable early premature responses. METHODS Extracellular and intracellular potentials were recorded following control and premature stimuli at a single site in aging human atrial bundles. We also measured cellular geometry, the distribution of connexins, and the distribution of collagenous septa. A model of the atrial bundles was constructed based on the morphological results. Action potential propagation and the sodium current were analyzed following premature stimuli in the model. RESULTS Similar extracellular potential waveform responses occurred following early premature stimuli in the aging bundles and in the model. Variable premature conduction patterns were accounted for by the single model of aging atrial structure. A major feature of the model results was that the conduction events and the magnitude of the sodium current at multiple sites were very sensitive to small changes in the location and the timing of premature stimuli. CONCLUSION In aging human atrial bundles stimulated from only a single site, premature stimuli induce variable arrhythmogenic conduction responses. The generation of these responses is greatly enhanced by remodeling of cellular connectivity during aging. The results provide insight into sodium current-structural interactions as a general mechanism of arrhythmogenic atrial responses to premature stimuli. PMID:17275753

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

    EPA Science Inventory

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

  19. Sensitivity Analysis of Hierarchical Models for the Ages of Galactic Halo White Dwarfs

    NASA Astrophysics Data System (ADS)

    Si, S.; van Dyk, D. A.; von Hippel, T.

    2017-03-01

    The ages of white dwarfs are of great importance in stellar evolution. Si et al. developed a novel approach to increase the precision of such estimates by combining multiple white dwarfs in a Bayesian hierarchical model. In this paper, we further investigate the robustness of the Bayesian hierarchical model by performing a simulation study.

  20. Lens opacity based modelling of the age-related straylight increase.

    PubMed

    Rozema, Jos J; Sanchez, Victoria; Artal, Natalia; Gramajo, Ana L; Torres, Eduardo; Luna, Jose D; Iribarren, Rafael; Tassignon, Marie-José; Juarez, Claudio P

    2015-12-01

    This work studies ethnic and geographical differences in the age-related straylight increase by means of a stochastic model and unpublished lens opacity data of 559 residents of Villa Maria (Argentina), as well as data of 912 Indonesian subjects published previously by Husain et al. For both cohorts the prevalence of each type and grade of lens opacity was determined as a function of age, from which a stochastic model was derived capable of simulating the lens opacity prevalence for both populations. These simulated lens opacity data were then converted to estimated straylight by means of an equation derived from previously recorded data of 107 eyes with varying degrees of cataract. Based on these opacity templates 2500 random sets of subject age and lens opacity data were generated by the stochastic model for each dataset, from which estimated straylight could be calculated. For the Argentinian data the estimated straylight was found to closely resemble the published models for age-related straylight increase. For younger eyes the straylight variation of the model was the same as what was previously published (in both cases ±0.200logunits), which doubled in size for older eyes. For the Indonesian data, however, this age-related straylight increase was found to be fundamentally different from the published age model. This suggests that current normative curves for age-related straylight increase may not always be appropriate for non-European populations, and that the inter-individual straylight variations in young, healthy eyes may possibly be due to variations in lens opacities.

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

    PubMed

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

    2011-02-28

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

  2. Estimating Black Carbon Aging Time-Scales with a Particle-Resolved Aerosol Model

    SciTech Connect

    Riemer, Nicole; West, Matt; Zaveri, Rahul A.; Easter, Richard C.

    2010-01-13

    Understanding the aging process of aerosol particles is important for assessing their chemical reactivity, cloud condensation nuclei activity, radiative properties and health impacts. In this study we investigate the aging of black carbon containing particles in an idealized urban plume using a new approach, the particleresolved aerosol model PartMC-MOSAIC. We present a method to estimate aging time-scales using an aging criterion based on cloud condensation nuclei activation. The results show a separation into a daytime regime where condensation dominates and a nighttime regime where coagulation dominates. For the chosen urban plume scenario, depending on the supersaturation threshold, the values for the aging timescales vary between 0.06 hours and 10 hours during the day, and between 6 hours and 20 hours during the night.

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

    PubMed

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

    2015-01-01

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

  4. Lithium-ion Open Circuit Voltage (OCV) curve modelling and its ageing adjustment

    NASA Astrophysics Data System (ADS)

    Lavigne, L.; Sabatier, J.; Francisco, J. Mbala; Guillemard, F.; Noury, A.

    2016-08-01

    This paper is a contribution to lithium-ion batteries modelling taking into account aging effects. It first analyses the impact of aging on electrode stoichiometry and then on lithium-ion cell Open Circuit Voltage (OCV) curve. Through some hypotheses and an appropriate definition of the cell state of charge, it shows that each electrode equilibrium potential, but also the whole cell equilibrium potential can be modelled by a polynomial that requires only one adjustment parameter during aging. An adjustment algorithm, based on the idea that for two fixed OCVs, the state of charge between these two equilibrium states is unique for a given aging level, is then proposed. Its efficiency is evaluated on a battery pack constituted of four cells.

  5. Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models

    PubMed Central

    Brubaker, Aleah L.; Palmer, Jessica L.; Kovacs, Elizabeth J.

    2011-01-01

    In the elderly patient population, it has become increasingly evident that immune dysregulation is a contributing factor to age-related pathologies and their associated morbidity and mortality. In particular, elderly subjects are plagued by poor responses to infectious challenge and immunization and are at heightened risk for the development of autoimmune, neuroinflammatory and tumor-associated pathologies. Rodent models of aging and age-related disorders have been utilized to better describe how innate immune cell dysfunction contributes to these clinical scenarios. As the elderly population continues to increase in size, use of these aging rodent models to study immune dysregulation may translate into increased healthy living years for these individuals. PMID:22396887

  6. The effects of aging on the BTBR mouse model of autism spectrum disorder

    PubMed Central

    Jasien, Joan M.; Daimon, Caitlin M.; Wang, Rui; Shapiro, Bruce K.; Martin, Bronwen; Maudsley, Stuart

    2014-01-01

    Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including “Neural synaptic plasticity regulation” and “Neurotransmitter secretion regulation.” Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype. PMID:25225482

  7. The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.

    PubMed

    Yashin, A I; Arbeev, K G; Akushevich, I; Kulminski, A; Ukraintseva, S V; Stallard, E; Land, K C

    2012-06-01

    A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, we describe an approach to analyses of longitudinal data based on the use of stochastic process models of human aging, health, and longevity which allows for incorporating state of the art advances in aging research into the model structure. In particular, the model incorporates the notions of resistance to stresses, adaptive capacity, and "optimal" (normal) physiological states. To capture the effects of exposure to persistent external disturbances, the notions of allostatic adaptation and allostatic load are introduced. These notions facilitate the description and explanation of deviations of individuals' physiological indices from their normal states, which increase the chances of disease development and death. The model provides a convenient conceptual framework for comprehensive systemic analyses of aging-related changes in humans using longitudinal data and linking these changes with genotyping profiles, morbidity, and mortality risks. The model is used for developing new statistical methods for analyzing longitudinal data on aging, health, and longevity.

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

    NASA Astrophysics Data System (ADS)

    Harwood, Jeremy J.

    2017-04-01

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

  9. Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

    PubMed Central

    Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

    2016-01-01

    Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

  10. Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

    PubMed

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

    2013-10-01

    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 because of 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 life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine 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.

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

    PubMed Central

    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

  12. Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

    PubMed

    Khalil, Z; LeVasseur, S; Merhi, M; Helme, R D

    1997-11-01

    1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

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

    PubMed

    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.

  14. Normal and diseased personal eye modeling using age-appropriate lens parameters

    PubMed Central

    Chen, Ying-Ling; Shi, L.; Lewis, J. W. L.; Wang, M.

    2012-01-01

    Personalized eye modeling of normal and diseased eye conditions is attractive due to the recent availability of detailed ocular measurements in clinic environments and the promise of its medical and industrial applications. In the customized modeling, the optical properties of the crystalline lens including the gradient refractive index, the lens bio-geometry and orientation are typically assigned with average lens parameters from literature since typically they are not clinically available. Although, through the optical optimization by assigning lens parameters as variables, the clinical measured wavefront aberration can be achieved, the optimized lens biometry and orientation often end up at edges of the statistical distribution. Without an effective validation of these models today, the fidelity of the final lens (and therefore the model) remains questionable. To develop a more reliable customized model without detailed lens information, we incorporate age-appropriate lens parameters as the initial condition of optical optimization. A biconic lens optimization was first performed to provide a correct lens profile for accurate lower order aberration and then followed by the wavefront optimization. Clinical subjects were selected from all ages with both normal and diseased corneal and refractive conditions. 19 ammetropic eyes ( + 4D to −11D), and 16 keratoconus eyes (mild to moderate with cylinder 0.25 to 6D) were modeled. Age- and gender-corrected refractive index was evaluated. Final models attained the lens shapes comparable to the statistical distribution in their age. PMID:22714237

  15. Effect of aging and damage on the brain modelled by a phase transition

    NASA Astrophysics Data System (ADS)

    Miyazima, Sasuke; Sakakibara, Mitsuharu

    1992-03-01

    Aging and the effects of damage on the brain are considered on the basis of the Hopfield model. As the damage to the brain or the debility of neurons is increased by aging, a sudden change similar to critical phenomena is observed in the ability to retrieve information or in recognition. This type of critical behavior is very similar to the percolation phenomenon in physics. Furthermore the relearning effect, which corresponds to so-called rehabilitation, is discussed.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    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

  18. Revisiting gerontology's scrapbook: from Metchnikoff to the Spectrum Model of Aging.

    PubMed

    Martin, Diane J; Gillen, Laura L

    2014-02-01

    The historical roots of gerontology date to a time when old age was characterized as physical and mental decline. Nonetheless, Metchnikoff questioned the inevitability of this decline, believing that quality of life could be improved by broadening our understanding of the science of aging, a multifaceted concept that extends well beyond the biological science interpretation so prevalent in gerontology's history. This article examines foundational gerontological theories in an effort to unravel complex interactions that constitute physiological aging processes, the psychological manifestations of individual adaptation, and the importance of social and spiritual relationships in aging successfully. Evaluating these theories through an interdisciplinary lens will benefit scholars, researchers, and aging services professionals because it offers opportunities to extend gerontological concepts from theory to development of models that can ultimately be applied in common practice to promote successful aging, regardless of one's physical or cognitive health status. To that end, we propose the Spectrum Model of Aging. Utilizing components of game theory, we believe it offers a synergistic approach to improving quality of later life and thus promises to move the field of gerontology beyond disciplinary boundaries.

  19. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

  20. Groundwater ages in an alluvial aquifer: Confronting lumped parameter models (3H, CFCs and SF6) and numerical transport modeling.

    NASA Astrophysics Data System (ADS)

    Mouloudi, R.; Gourcy, L.; Kloppmann, W.; Violette, S.

    2012-04-01

    Groundwater age dating using tritium and dissolved gases was undertaken in an alluvial aquifer to determine groundwater transit time and flow rate as key parameters for assessing diffuse nitrate pollution.The studied site of about 260 km2 is crossed by the Ain River and bordered by the Rhône River which is the natural drain for the aquifer. It is mainly recharged by precipitation but also receives water from the Dombes plain (NW and W), intensively cultivated, and from the Bugey and Jura karstic mountains (NE and E part). In this study, we investigated the relevance of the gas-tracers CFCs and SF6 as age dating tools in alluvial shallow aquifers. The exponential model was chosen to conceptualize the alluvial aquifer recharge, 3H also used. Age-dating gave a mean recharge date of 5 to 18 years. CFCs, SF6 and 3H age estimation was confronted with the results of 2D transport modelling. Lumped parameter models were used to estimate the distribution of CFC and SF6 ages. Groundwater age is a measurable quantity, provided many assumptions. One of the underlying questions is the physical meaning of "ages" obtained by the lumped parameter models. Indeed, knowledge of an apparent age does not necessarily imply knowledge of the groundwater residence time. An independent approach of groundwater age determination is based on solving the solute transport problem. Few studies seek to compare the hydrodynamic and tracers approaches. This comparison aims to increase our hydrogeological understanding of the Ain alluvial plain and to better define " groundwater age" and its meanings. The hydrodynamic modelling was performed using MARTHE code (Thiéry, 2004). It was calibrated over a period of 8 years at a 10 days' time step. Results of the transitory regime calibration are satisfactory and allowed the use of this model for solute transport of 3H, CFCs and SF6. Different approaches are possible for the comparison of tracer and hydrodynamic models. The first is to reproduce the tracer

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  3. AgedCare+GP: description and evaluation of an in-house model of general practice in a residential aged-care facility.

    PubMed

    Pain, Tilley; Stainkey, Lesley; Chapman, Sue

    2014-01-01

    This paper describes a medical model to provide in-house GP services to residents of aged-care facilities. Access to GP services for aged-care residents is decreasing, partially due to the changing demographic of the Australian GP workforce. The model we have developed is an in-house GP (AgedCare+GP) trialled in a publicly funded residential aged-care facility (RACF). The service model was based on the GP cooperative used in our after-hours general practice (AfterHours+GP). Briefly, the service model involves rostering a core group of GPs to provide weekly sessional clinics at the RACF. Financial contributions from appropriate Medicare Benefits Schedule (MBS) items for aged-care planning (including chronic conditions) provided adequate funds to operate the clinic for RACF residents. Evaluation of the service model used the number of resident transfers to the local emergency department as the primary outcome measure. There were 37 transfers of residents in the 3 months before the commencement of the AgedCare+GP and 11 transfers over a 3-month period at the end of the first year of operation; a reduction of almost 70%. This project demonstrates that AgedCare+GP is a successful model for GP service provision to RACF residents, and it also reduces the number of emergency department transfers.

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

    NASA Astrophysics Data System (ADS)

    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 R0<1, and there exists at least one endemic equilibrium and that the disease is uniformly persistent if R0>1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  6. Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age.

    PubMed

    Li, Xiaoming; Zhang, Jane H; Betts, Robert F; Morrison, Vicki A; Xu, Ruifeng; Itzler, Robbin F; Acosta, Camilo J; Dasbach, Erik J; Pellissier, James M; Johnson, Gary R; Chan, Ivan S F

    2015-03-17

    Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.

  7. Multiple morbidities in companion dogs: a novel model for investigating age-related disease

    PubMed Central

    Jin, Kelly; Hoffman, Jessica M.; Creevy, Kate E.; O’Neill, Dan G.; Promislow, Daniel E.L.

    2016-01-01

    The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality. PMID:27876455

  8. A New, Discontinuous 2 Phases of Aging Model: Lessons from Drosophila melanogaster

    PubMed Central

    Tricoire, Hervé; Rera, Michael

    2015-01-01

    Aging is commonly described as being a continuous process affecting progressively organisms as time passes. This process results in a progressive decrease in individuals fitness through a wide range of both organismal–decreased motor activity, fertility, resistance to stress–and molecular phenotypes–decreased protein and energy homeostasis, impairment of insulin signaling. In the past 20 years, numerous genes have been identified as playing a major role in the aging process, yet little is known about the events leading to that loss of fitness. We recently described an event characterized by a dramatic increase of intestinal permeability to a blue food dye in aging flies committed to die within a few days. Importantly, flies showing this so called ‘Smurf’ phenotype are the only ones, among a population, to show various age-related changes and exhibit a high-risk of impending death whatever their chronological age. Thus, these observations suggest that instead of being one continuous phenomenon, aging may be a discontinuous process well described by at least two distinguishable phases. In this paper we addressed this hypothesis by implementing a new 2 Phases of Aging mathematiCal model (2PAC model) to simulate longevity curves based on the simple hypothesis of two consecutive phases of lifetime presenting different properties. We first present a unique equation for each phase and discuss the biological significance of the 3 associated parameters. Then we evaluate the influence of each parameter on the shape of survival curves. Overall, this new mathematical model, based on simple biological observations, is able to reproduce many experimental longevity curves, supporting the existence of 2 phases of aging exhibiting specific properties and separated by a dramatic transition that remains to be characterized. Moreover, it indicates that Smurf survival can be approximated by one single constant parameter for a broad range of genotypes that we have tested under

  9. Periodic and quasi-periodic behavior in resource-dependent age structured population models.

    PubMed

    Dilão, R; Domingos, T

    2001-03-01

    To describe the dynamics of a resource-dependent age structured population, a general non-linear Leslie type model is derived. The dependence on the resources is introduced through the death rates of the reproductive age classes. The conditions assumed in the derivation of the model are regularity and plausible limiting behaviors of the functions in the model. It is shown that the model dynamics restricted to its omega-limit sets is a diffeomorphism of a compact set, and the period-1 fixed points of the model are structurally stable. The loss of stability of the non-zero steady state occurs by a discrete Hopf bifurcation. Under general conditions, and after the loss of stability of the structurally stable steady states, the time evolution of population numbers is periodic or quasi-periodic. Numerical analysis with prototype functions has been performed, and the conditions leading to chaotic behavior in time are discussed.

  10. 230Th-234U Model-Ages of Some Uranium Standard Reference Materials

    SciTech Connect

    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.

  11. Modeling early-onset post-ischemic seizures in aging mice.

    PubMed

    Wu, Chiping; Wang, Justin; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2015-09-01

    Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals.

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

    PubMed

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

    2006-04-01

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

  13. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    PubMed

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    Ward, Logan Timothy; Hackenberg, Robert Errol

    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.

  16. Neurogenesis in a rat model of age-related cognitive decline.

    PubMed

    Bizon, J L; Lee, H J; Gallagher, M

    2004-08-01

    Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

  17. Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model

    PubMed Central

    Spiers, Helen; Hannon, Eilis; Wells, Sara; Williams, Brenda; Fernandes, Cathy; Mill, Jonathan

    2016-01-01

    Epigenetic disruption has been implicated in many diseases of aging, and age-associated DNA methylation changes at specific genomic loci in humans are strongly correlated with chronological age. The aim of this study was to explore the specificity of selected age-associated differentially methylated positions (aDMPs) identified in human epidemiological studies by quantifying DNA methylation across multiple tissues in homologous regions of the murine genome. We selected four high-confidence aDMPs (located in the vicinity of the ELOVL2, GLRA1, MYOD1 and PDE4C genes) and quantified DNA methylation across these regions in four tissues (blood, lung, cerebellum and hippocampus) from male and female C57BL/6J mice, ranging in age from fetal (embryonic day 17) to 630 days. We observed tissue-specific age-associated changes in DNA methylation that was directionally consistent with those observed in humans. These findings lend further support to the notion that changes in DNA methylation are associated with chronological age and suggest that these processes are often conserved across tissues and between mammalian species. Our data highlight the relevance of utilizing model systems, in which environmental and genetic influences can be carefully controlled, for the further study of these phenomena. PMID:26861500

  18. Mechanisms of Muscle Denervation in Aging: Insights from a Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Park, Kevin H.J

    2015-01-01

    Muscle denervation at the neuromuscular junction (NMJ) is thought to be a contributing factor in age-related muscle weakness. Therefore, understanding the mechanisms that modulate NMJ innervation is a key to developing therapies to combat age-related muscle weakness affecting the elderly. Two mouse models, one lacking the Cu/Zn superoxide dismutase (SOD1) gene and another harboring the transgenic mutant human SOD1 gene, display progressive changes at the NMJ, including muscle endplate fragmentation, nerve terminal sprouting, and denervation. These changes at the NMJ share many of the common features observed in the NMJs of aged mice. In this review, research findings demonstrating the effects of PGC-1α, IGF-1, GDNF, MyoD, myogenin, and miR-206 on NMJ innervation patterns in the G93A SOD1 mice will be highlighted in the context of age-related muscle denervation. PMID:26425392

  19. Constitutive Modeling and Testing of Polymer Matrix Composites Incorporating Physical Aging at Elevated Temperatures

    NASA Technical Reports Server (NTRS)

    Veazie, David R.

    1998-01-01

    Advanced polymer matrix composites (PMC's) are desirable for structural materials in diverse applications such as aircraft, civil infrastructure and biomedical implants because of their improved strength-to-weight and stiffness-to-weight ratios. For example, the next generation military and commercial aircraft requires applications for high strength, low weight structural components subjected to elevated temperatures. A possible disadvantage of polymer-based composites is that the physical and mechanical properties of the matrix often change significantly over time due to the exposure of elevated temperatures and environmental factors. For design, long term exposure (i.e. aging) of PMC's must be accounted for through constitutive models in order to accurately assess the effects of aging on performance, crack initiation and remaining life. One particular aspect of this aging process, physical aging, is considered in this research.

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

    PubMed

    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.

  1. A Validated Normative Model for Human Uterine Volume from Birth to Age 40 Years

    PubMed Central

    Ginbey, Eleanor; Chowdhury, Moti M.; Bath, Louise E.; Anderson, Richard A.; Wallace, W. Hamish B.

    2016-01-01

    Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non-invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone. The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume. PMID:27295032

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

    PubMed Central

    Lökk, Johan

    2014-01-01

    Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson's disease (PD). The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson's Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging. PMID:25225618

  3. Limiting extensibility constitutive model with distributed fibre orientations and ageing of abdominal aorta.

    PubMed

    Horný, Lukáš; Netušil, Marek; Daniel, Matěj

    2014-10-01

    The abdominal aorta is susceptible to age-related pathological changes (arteriosclerosis, atherosclerosis, aneurysm, and tortuosity). Computational biomechanics and mechanobiology provide models capable of predicting mutual interactions between a changing mechanical environment and patho-physiological processes in ageing. However, a key factor is a constitutive equation which should reflect the internal tissue architecture. Our study investigates three microstructurally-motivated invariant-based hyperelastic anisotropic models suitable for description of the passive mechanical behaviour of the human abdominal aorta at a multiaxial state of stress known from recent literature. The three adopted models have also been supplemented with a newly proposed constitutive model (limiting extensibility with fibre dispersion). All models additively decouple the mechanical response of the isotropic (elastin and smooth muscle cells represented by the neo-Hookean term) and the anisotropic (collagen) parts. Two models use exponential functions to capture large strain stiffening ascribed to the engagement of collagen fibres into the load-bearing process. The other two models are based on the concept of limiting extensibility. Perfect alignment of reinforcing fibres with two preferred directions as well as fibre dispersion are considered. Constitutive models are calibrated to the inflation-extension response adopted from the literature based on the computational model of the residually-stressed thick-walled tube. A correlation analysis of determined material parameters was performed to reveal dependence on the age. The results of the nonlinear regression suggest that limiting fibre extensibility is the concept which is suitable to be used for the constitutive description of the aorta at multiaxial stress states and is highly sensitive to ageing-induced changes in mechanical response.

  4. Frontiers of Model Animals for Neuroscience:Two Prosperous Aging Model Animals forPromoting Neuroscience Research

    PubMed Central

    Ito, Koichi

    2013-01-01

    A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer’s disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer’s disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future. PMID:24172191

  5. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

    PubMed Central

    Fujitsuka, N; Asakawa, A; Morinaga, A; Amitani, M S; Amitani, H; Katsuura, G; Sawada, Y; Sudo, Y; Uezono, Y; Mochiki, E; Sakata, I; Sakai, T; Hanazaki, K; Yada, T; Yakabi, K; Sakuma, E; Ueki, T; Niijima, A; Nakagawa, K; Okubo, N; Takeda, H; Asaka, M; Inui, A

    2016-01-01

    Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID:26830139

  6. Predicting Age-Appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically Based Pharmacokinetic Modeling

    EPA Science Inventory

    The capability of physiologically based pharmacokinetic models to incorporate age-appropriate physiological and chemical-specific parameters was utilized to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages of rats.

  7. Random regression model of growth during the first three months of age in Spanish Merino sheep.

    PubMed

    Molina, A; Menéndez-Buxadera, A; Valera, M; Serradilla, J M

    2007-11-01

    A total of 88,727 individual BW records of Spanish Merino lambs, obtained from 30,214 animals between 2 and 92 d of age, were analyzed using a random regression model (RRM). These animals were progeny of 546 rams and 15,586 ewes raised in 30 flocks, between 1992 and 2002, with a total of 45,941 animals in the pedigree. The contemporary groups (animals of the same flock, year, and season, with 452 levels), the lambing number (11 levels), the combination sex of lambs with type of litter (4 levels), and a fixed regression coefficient of age on BW were included as fixed effects. A total of 7 RRM were compared, and the best fit was obtained for a model of order 3 for the direct and maternal genetic effects and for the individual permanent environmental effect. For the maternal permanent environmental effect the best model had an order 2. The residual variance was assumed to be heterogeneous with 10 age classes; the covariance between both genetic effects was included. According to the results of the selected RRM, the heritability for both genetic effects (h(a)2 and h(m)2) increased with age, with estimates of 0.123 to 0.186 for h(a)2 and of 0.059 to 0.108 for h(m)2. The correlations between direct and genetic maternal effects were -0.619 to -0.387 during the first 45 d of age and decreased as age increased, until reaching values from -0.366 to -0.275 between 45 to 75 d of age. Important changes in ranking of the animals were found based on the breeding value estimation with the current method and with the random regression procedure. The use of RRM to analyze the genetic trajectory of growth in this population of Merino sheep is highly recommended.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  9. Age at first birth and fathers' subsequent health: evidence from sibling and twin models.

    PubMed

    Pudrovska, Tetyana; Carr, Deborah

    2009-06-01

    Using a sample of 540 siblings and twins from the National Survey of Midlife Development in the United States, this study examines the relationship between the age at which men become biological fathers and their subsequent health. The analysis includes both between-family models that treat brothers as independent observations and within-family models that account for unobserved genetic and early-life environmental endowments shared by brothers within families. Findings indicate that age at first birth has a positive, linear effect on men's health, and this relationship is not explained by the confounding influences of unobserved early-life characteristics. However, the effect of age at first birth on fathers' health is explained by men's socioeconomic and family statuses. Whereas most research linking birth timing to specific diseases focuses narrowly on biological mechanisms among mothers, this study demonstrates the importance of reproductive decisions for men's health and well-being.

  10. Compact modeling of total ionizing dose and aging effects in MOS technologies

    DOE PAGES

    Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

    2015-06-18

    This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimentalmore » I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.« less

  11. Compact modeling of total ionizing dose and aging effects in MOS technologies

    SciTech Connect

    Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

    2015-06-18

    This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimental I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.

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

    PubMed

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

    2013-06-01

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

  13. Neuroscientists as Cartographers: Mapping the Crossroads of Gonadal Hormones, Memory and Age Using Animal Models

    PubMed Central

    Bimonte-Nelson, Heather A.; Acosta, Jazmin I.; Talboom, Joshua S.

    2010-01-01

    Cognitive function is multidimensional and complex, and research in multiple species indicates it is considerably impacted by age and gonadal hormone milieu. One domain of cognitive function particularly susceptible to age-related decrements is spatial memory. Gonadal hormones can alter spatial memory, and they are potent modulators of brain microstructure and function in many of the same brain areas affected by aging. In this paper, we review decades of animal and human literature to support a tertiary model representing interactions between gonadal hormones, spatial cognition and age given that: 1) gonadal hormones change with age, 2) age impacts spatial learning and memory, and 3) gonadal hormones impact spatial learning and memory. While much has been discovered regarding these individual tenets, the compass for future aging research points toward clarifying the interactions that exist between these three points, and understanding mediating variables. Indeed, identifying and aligning the various components of the complex interactions between these tenets, including evaluations using basic science, systems, and clinical perspectives, is the optimal approach to attempt to converge the many findings that may currently appear contradictory. In fact, as discoveries are being made it is becoming clear that the findings across studies that appear contradictory are not contradictory at all. Rather, there are mediating variables that are influencing outcome and affecting the extent, and even the direction, of the effects that gonadal hormones have on cognition during aging. These mediating variables are just starting to be understood. By aligning basic scientific discoveries with clinical interpretations, we can maximize the opportunities for discoveries and subsequent interventions to allow individuals to “optimize their aging” and find their own map to cognitive health as aging ensues. PMID:20877209

  14. Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

    PubMed Central

    Kang, Ji Young; Lee, Sook Young; Rhee, Chin Kook; Kim, Seung Joon; Kwon, Soon Seog; Kim, Young Kyoon

    2013-01-01

    Background and objectives The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8–12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. Periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice. PMID:24204129

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  16. The reemergence of long-term potentiation in aged Alzheimer’s disease mouse model

    PubMed Central

    Huh, Seonghoo; Baek, Soo-Ji; Lee, Kyung-Hwa; Whitcomb, Daniel J.; Jo, Jihoon; Choi, Seong-Min; Kim, Dong Hyun; Park, Man-Seok; Lee, Kun Ho; Kim, Byeong C.

    2016-01-01

    Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID:27377368

  17. A Second Note on Ageing in a Library Circulation Model: The Correlation Structure.

    ERIC Educational Resources Information Center

    Burrell, Quentin L.

    1986-01-01

    Correlation structure of the Burrell and Cane mixed Poisson model for library loans with aging is presented and illustrated by data from University of Sussex. The approach is compared and contrasted with that originally formulated by Morse and recently reevaluated by Beheshti and Tague. Directions for future investigations are suggested. (Author)

  18. Modeling the aging heart: from local respiratory defects to global rhythm disturbances.

    PubMed

    Khrapko, Konstantin; Trayanova, Natalia; Nattel, Stanley

    2015-05-05

    In this issue, Baris et al. (2015) describe cardiac rhythm abnormalities in a mouse model of mitochondrial dysfunction in widely distributed cells of the aging human heart. How do a few metabolically challenged cells disrupt cardiac rhythm? We suggest that these cells provide "crystallization centers" for latent dysfunctional zones to allow arrhythmia emergence.

  19. On the Problem of the Numerical Model Construction of Zero-Age Substars

    NASA Astrophysics Data System (ADS)

    Zakhozhaj, V. A.; Blokhina, M. D.; Pysarenko, A. I.; Yatsenko, A. A.; Slusarenko, Yu. V.

    The numerical modelling of substars inner structure is analysed and main definitions are suggested. Here we present results of calculation of degeneracy parameter psi, permitting to make calculate the dependence of number of free electrons on function temperature and density typical interior of zero-age substars (ZAS).

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

    EPA Science Inventory

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

  1. Rowe and Kahn's Model of Successful Aging Revisited: Positive Spirituality--The Forgotten Factor.

    ERIC Educational Resources Information Center

    Crowther, Martha R.; Parker, Michael W.; Achenbaum, W. A.; Larimore, Walter L.; Koenig, Harold G.

    2002-01-01

    Explains the concept of positive spirituality and offers evidence that links positive spirituality with health. Describes effective partnerships between health professionals and religious communities and summarized the information as a basis for strengthening the existing successful aging model proposed by Rowe and Kahn. (Contains 59 references…

  2. Education for Positive Ageing: A Partnership Model for Effecting Sustainable Outcomes.

    ERIC Educational Resources Information Center

    Feldman, Susan; Mahoney, Helen; Seedsman, Terence

    2002-01-01

    Pre/posttest results from 282 elementary students who interacted with older adults and observations by teachers and elders revealed changes in attitudes and awareness about aging. In stage 2, preservice teachers and older adults worked together in elementary schools. A model for sustainable lifespan curriculum involving elementary schools, teacher…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

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

    1977-01-01

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

  6. Crisis Model for Older Adults: Special Considerations for an Aging Population

    ERIC Educational Resources Information Center

    Jungers, Christin M.; Slagel, Leslie

    2009-01-01

    As the U.S. population ages, counselors must begin structuring their interactions to meet the unique needs of older adults, especially in the area of crisis intervention. The purposes of this article are to draw attention to the rapidly growing, often disregarded older population and to introduce the Crisis Model for Older Adults (CM-OA), an…

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

    ERIC Educational Resources Information Center

    Scharlach, Andrew; Graham, Carrie; Lehning, Amanda

    2012-01-01

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

  8. Multi-State Physics Models of Aging Passive Components in Probabilistic Risk Assessment

    SciTech Connect

    Unwin, Stephen D.; Lowry, Peter P.; Layton, Robert F.; Heasler, Patrick G.; Toloczko, Mychailo B.

    2011-03-13

    Multi-state Markov modeling has proved to be a promising approach to estimating the reliability of passive components - particularly metallic pipe components - in the context of probabilistic risk assessment (PRA). These models consider the progressive degradation of a component through a series of observable discrete states, such as detectable flaw, leak and rupture. Service data then generally provides the basis for estimating the state transition rates. Research in materials science is producing a growing understanding of the physical phenomena that govern the aging degradation of passive pipe components. As a result, there is an emerging opportunity to incorporate these insights into PRA. This paper describes research conducted under the Risk-Informed Safety Margin Characterization Pathway of the Department of Energy’s Light Water Reactor Sustainability Program. A state transition model is described that addresses aging behavior associated with stress corrosion cracking in ASME Class 1 dissimilar metal welds – a component type relevant to LOCA analysis. The state transition rate estimates are based on physics models of weld degradation rather than service data. The resultant model is found to be non-Markov in that the transition rates are time-inhomogeneous and stochastic. Numerical solutions to the model provide insight into the effect of aging on component reliability.

  9. Age and regulatory focus determine preferences for health-related role models.

    PubMed

    Lockwood, Penelope; Chasteen, Alison L; Wong, Carol

    2005-09-01

    The authors hypothesized that the effectiveness of role models varies across the adult life span because of differences in health-related regulatory orientations. Because young adults have strong health-related promotion orientations, they should be motivated by positive models who illustrate the benefits of good health. Because older adults have more balanced health-related promotion and prevention orientations, they should be motivated not only by positive models but also by negative models who illustrate the costs of poor health. Results indicated that both young and older adults perceived positive models to be motivating, but older adults found negative models to be more motivating than did young adults. Age differences in responses to negative models were partially mediated by differences in health-related prevention orientation.

  10. Aging Well Socially through Engagement with Life: Adapting Rowe and Kahn's Model of Successful Aging to Chinese Cultural Context

    ERIC Educational Resources Information Center

    Ng, Sik Hung; Cheung, Chau-Kiu; Chong, Alice M. L.; Woo, Jean; Kwan, Alex Y. H.; Lai, Stephanie

    2011-01-01

    Although aging well socially (Engagement with Life) is as important as aging well personally (Illness Avoidance and Functioning) (Rowe & Kahn, 1998), it has received less research attention. A Caring (CE) and a Productive (PE) form of Engagement were derived from an analysis of Chinese cultural meanings of engagement, and combined with Illness…

  11. Modeling shortwave solar radiation using the JGrass-NewAge system

    NASA Astrophysics Data System (ADS)

    Formetta, G.; Rigon, R.; Chávez, J. L.; David, O.

    2013-07-01

    This paper presents two new modeling components based on the object modeling system v3 (OMS3) for the calculation of the shortwave incident radiation (Rsw↓) on complex topography settings, and the implementation of several ancillary tools. The first component, NewAGE-SwRB, accounts for elevation slope, aspect, shadow of the sites, and uses suitable parameterization for obtaining the cloudless irradiance. A second component, NewAGE-DEC-MOD's is implemented to estimate the irradiance reduction due to the presence of clouds according to three parameterizations. To obtain a working modeling composition that is comparable with ground data at measurement stations the two components are connected to a kriging component. With the help of an additional component, NewAGE-V (verification package), the performance of modeled (Rsw↓) is quantitatively evaluated. The two components (and the various parameterizations they contain) are tested using the data from three basins, and some simple verification tests were carried out to assess the goodness of the methods used. Moreover, a raster mode test is performed in order to show the capability of the system in providing solar radiation raster maps. The components are part of a larger system, JGrass-NewAGE, their input and outputs are geometrical objects immediately displayed in a geographical information system (GIS). They can be used seamlessly with the various modeling solutions available in JGrass-NewAGE for the estimation of long wave radiation, evapotranspiration, and snow melting, as well as standalone components to just estimate shortwave radiation for various uses. The modularity of the approach leads to more accurate physical-statistical studies aimed to assess in depth the components' performances and extends their results spatially, without the necessity of recoding any part of the component.

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

    Hemphill, Geralyn M; Hackenberg, Robert E

    2009-01-01

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

  14. Premature aging-related peripheral neuropathy in a mouse model of progeria.

    PubMed

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

    2011-08-01

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

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

    USGS Publications Warehouse

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

    2008-01-01

    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 14C ages, along with the 137Cs and 210Pb activities of recent sediment, we evaluated different models to determine the age-depth relation of the core, and to determine the age of each tephra deposit. The selected age model is based on a mixed-effect regression that was passed through the adjusted tephra-free depth of each dated layer. The estimated age uncertainty of the 67 tephras averages ??105 yr (95% confidence intervals). Tephra-fall frequency at Bear Lake was among the highest during the past 500 yr, with eight tephras deposited compared to an average of 3.7/500 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 one every 130 yr. ?? 2007 Elsevier Ltd. All rights reserved.

  16. A stress-induced cellular aging model with postnatal neural stem cells.

    PubMed

    Dong, C-M; Wang, X-L; Wang, G-M; Zhang, W-J; Zhu, L; Gao, S; Yang, D-J; Qin, Y; Liang, Q-J; Chen, Y-L; Deng, H-T; Ning, K; Liang, A-B; Gao, Z-L; Xu, J

    2014-03-13

    Aging refers to the physical and functional decline of the tissues over time that often leads to age-related degenerative diseases. Accumulating evidence implicates that the senescence of neural stem cells (NSCs) is of paramount importance to the aging of central neural system (CNS). However, exploration of the underlying molecular mechanisms has been hindered by the lack of proper aging models to allow the mechanistic examination within a reasonable time window. In the present study, we have utilized a hydroxyurea (HU) treatment protocol and effectively induced postnatal subventricle NSCs to undergo cellular senescence as determined by augmented senescence-associated-β-galactosidase (SA-β-gal) staining, decreased proliferation and differentiation capacity, increased G0/G1 cell cycle arrest, elevated reactive oxygen species (ROS) level and diminished apoptosis. These phenotypic changes were accompanied by a significant increase in p16, p21 and p53 expression, as well as a decreased expression of key proteins in various DNA repair pathways such as xrcc2, xrcc3 and ku70. Further proteomic analysis suggests that multiple pathways are involved in the HU-induced NSC senescence, including genes related to DNA damage and repair, mitochondrial dysfunction and the increase of ROS level. Intriguingly, compensatory mechanisms may have also been initiated to interfere with apoptotic signaling pathways and to minimize the cell death by downregulating Bcl2-associated X protein (BAX) expression. Taken together, we have successfully established a cellular model that will be of broad utilities to the molecular exploration of NSC senescence and aging.

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:27534441

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

    SciTech Connect

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

    2007-02-25

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

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

    PubMed

    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.

  20. Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease

    PubMed Central

    Kerr, F.; Augustin, H.; Piper, M.D.W.; Gandy, C.; Allen, M.J.; Lovestone, S.; Partridge, L.

    2011-01-01

    Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aβ42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aβ and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD. PMID:19969390

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

    PubMed

    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.

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

    PubMed Central

    Demontis, Fabio; Piccirillo, Rosanna; Goldberg, Alfred L.; Perrimon, Norbert

    2013-01-01

    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. PMID:24092876

  3. Stability analysis of a model gene network links aging, stress resistance, and negligible senescence

    PubMed Central

    Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I.; Reis, Robert J. Shmookler; Fedichev, Peter

    2015-01-01

    Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz “law” of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals. PMID:26316217

  4. Modeling the Multiday Evolution and Aging of Secondary Organic Aerosol During MILAGRO 2006

    NASA Astrophysics Data System (ADS)

    Dzepina, K.; Cappa, C. D.; Volkamer, R.; Madronich, S.; Decarlo, P. F.; Zaveri, R. A.; Jimenez, J. L.

    2010-12-01

    In this study we apply several recently-proposed models to the evolution of secondary organic aerosols (SOA) and organic gases advected from downtown Mexico City at an altitude of ~3.5 km during three days of aging. We constrain the model with and compare its results to available observations. The model SOA formed from oxidation of volatile organic compounds (V-SOA) alone cannot explain the observed mass loadings in aged pollution. Over the regional scale ~5% of the model SOA is due to the low-NOx aromatic V-SOA pathway, which has a higher yield and produces comparably “low-volatility” species that remain in the particle phase as dilution proceeds and more volatile components evaporate. The model SOA formed from oxidation of both semivolatile and intermediate volatility organic vapors (SI-SOA) accounts for most of the predicted SOA mass concentration. With the SI-SOA parameterization of Robinson et al. (2007) the model matches the observed SOA mass, but its O/C is too low by a factor of 2. With the parameterization of Grieshop et al. (2009) the total SOA mass is overpredicted by a factor of ~2 but O/C and volatility are much closer to the observations. Heating or dilution of the air results in evaporation of a substantial fraction of the model SOA; this fraction is reduced by aging although differently for heating vs. dilution. Finally, lifting of the airmass to the free-troposphere during dry convection results in a substantial increase of SOA by condensation of semivolatile vapors, with this effect being reduced by aging.

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

    PubMed

    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.

  6. Racial disparities in age at time of homicide victimization: a test of the multiple disadvantage model.

    PubMed

    Lo, Celia C; Howell, Rebecca J; Cheng, Tyrone C

    2015-01-01

    This study sought the factors associated with race/ethnicity disparities in the age at which homicide deaths tend to occur. We used the multiple disadvantage model to take race into account as we evaluated associations between age at time of homicide victimization and several social structural, mental health-related, and lifestyle factors. Data were derived from the 1993 National Mortality Followback Survey, a cross-sectional interview study of spouses, next of kin, other relatives, and close friends of individuals 15 years and older who died in the United States in 1993. Our results showed age at time of homicide mortality to be related to the three types of factors; race moderated some of these relationships. In general, being employed, married, and a homeowner appeared associated with reduced victimization while young. The relationship of victimization age and employment was not uniform across racial groups, nor was the relationship of victimization age and marital status uniform across groups. Among Blacks, using mental health services was associated with longer life. Homicide by firearm proved important for our Black and Hispanic subsamples, while among Whites, alcohol's involvement in homicide exerted significant effects. Our results suggest that programs and policies serving the various racial/ethnic groups can alleviate multiple disadvantages relevant in homicide victimization at an early age.

  7. The budding yeast, Saccharomyces cerevisiae, as a model for aging research: a critical review.

    PubMed

    Gershon, H; Gershon, D

    2000-12-01

    In this review we discuss the yeast as a paradigm for the study of aging. The budding yeast Saccharomyces cerevisiae, which can proliferate in both haploid and diploid states, has been used extensively in aging research. The budding yeast divides asymmetrically to form a 'mother' cell and a bud. Two major approaches, 'budding life span' and 'stationary phase' have been used to determine 'senescence' and 'life span' in yeast. Discrepancies observed in metabolic behavior and longevity between cells studied by these two systems raise questions of how 'life span' in yeast is defined and measured. Added to this variability in experimental approach and results is the variety of yeast strains with different genetic make up used as 'wild type' and experimental organisms. Another problematic genetic point in the published studies on yeast is the use of both diploid and haploid strains. We discuss the inherent, advantageous attributes that make the yeast an attractive choice for modern biological research as well as certain pitfalls in the choice of this model for the study of aging. The significance of the purported roles of the Sir2 gene, histone deacetylases, gene silencing, rDNA circles and stress genes in determination of yeast 'life span' and aging is evaluated. The relationship between cultivation conditions and longevity are assessed. Discrepancies between the yeast and mammalian systems with regard to aging are pointed out. We discuss unresolved problems concerning the suitability of the budding yeast for the study of basic aging phenomena.

  8. Modelling the p53/p66Shc Aging Pathway in the Shortest Living Vertebrate Nothobranchius Furzeri

    PubMed Central

    Priami, Chiara; De Michele, Giulia; Cotelli, Franco; Cellerino, Alessandro; Giorgio, Marco; Pelicci, Pier Giuseppe; Migliaccio, Enrica

    2015-01-01

    Oxidative stress induced by reactive oxygen species (ROS) increases during lifespan and is involved in aging processes. The p66Shc adaptor protein is a master regulator of oxidative stress response in mammals. Ablation of p66Shc enhances oxidative stress resistance both in vitro and in vivo. Most importantly, it has been demonstrated that its deletion retards aging in mice. Recently, new insights in the molecular mechanisms involving p66Shc and the p53 tumor suppressor genes were given: a specific p66Shc/p53 transcriptional regulation pathway was uncovered as determinant in oxidative stress response and, likely, in aging. p53, in a p66Shc-dependent manner, negatively downregulates the expression of 200 genes which are involved in the G2/M transition of mitotic cell cycle and are downregulated during physiological aging. p66Shc modulates the response of p53 by activating a p53 isoform (p44/p53, also named Delta40p53). Based on these latest results, several developments are expected in the future, as the generation of animal models to study aging and the evaluation of the use of the p53/p66Shc target genes as biomarkers in aging related diseases. The aim of this review is to investigate the conservation of the p66Shc and p53 role in oxidative stress between fish and mammals. We propose to approach this study trough a new model organism, the annual fish Nothobranchius furzeri, that has been demonstrated to develop typical signs of aging, like in mammals, including senescence, neurodegeneration, metabolic disorders and cancer. PMID:25821638

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

    PubMed

    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.

  10. A two-component Bayesian mixture model to identify implausible gestational age

    PubMed Central

    Mohammadian-Khoshnoud, Maryam; Moghimbeigi, Abbas; Faradmal, Javad; Yavangi, Mahnaz

    2016-01-01

    Background: Birth weight and gestational age are two important variables in obstetric research. The primary measure of gestational age is based on a mother’s recall of her last menstrual period. This recall may cause random or systematic errors. Therefore, the objective of this study is to utilize Bayesian mixture model in order to identify implausible gestational age. Methods: In this cross-sectional study, medical documents of 502 preterm infants born and hospitalized in Hamadan Fatemieh Hospital from 2009 to 2013 were gathered. Preterm infants were classified to less than 28 weeks and 28 to 31 weeks. A two-component Bayesian mixture model was utilized to identify implausible gestational age; the first component shows the probability of correct and the second one shows the probability of incorrect classification of gestational ages. The data were analyzed through OpenBUGS 3.2.2 and 'coda' package of R 3.1.1. Results: The mean (SD) of the second component of less than 28 weeks and 28 to 31 weeks were 1179 (0.0123) and 1620 (0.0074), respectively. These values were larger than the mean of the first component for both groups which were 815.9 (0.0123) and 1061 (0.0074), respectively. Conclusion: Errors occurred in recording the gestational ages of these two groups of preterm infants included recording the gestational age less than the actual value at birth. Therefore, developing scientific methods to correct these errors is essential to providing desirable health services and adjusting accurate health indicators. PMID:28210605

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

    SciTech Connect

    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 /sup 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 /sup 131/I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K(exp(-..mu../sub 1/t) - exp(-..mu../sub 2/t)) (..mu..Ci), where ..mu../sub 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/..mu..Ci-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.

  12. Modelling of the aging behavior of polyamide 12 powder during laser melting process

    NASA Astrophysics Data System (ADS)

    Drummer, Dietmar; Wudy, Katrin; Drexler, Maximilian

    2015-05-01

    Concerning individualization, the requirements to products have increased. Additive manufacturing technologies, such as selective laser melting allow manufacturing of complex parts without tools and forms. Due to this additive manufacturing processes comply, in opposite to conventional techniques, with these increased demands on processing technology. Due to the high temperature during processing, a degradation of the used plastic powder occurs. The non-molten material in the building chamber, the so-called partcake, can be removed after building from the finished component and reused for another process. To realize reproducible part properties refreshing of partcake powder with 30 up to 50 % virgin powder is necessary. However, these refreshing strategies lead to varying component properties due to an undefined aging state. Previous investigations on oven aged powder for selective laser melting showed for short periods of storage near the melting point thermally induced post condensation is the predominate aging effect. Due to post condensation the molecular weight and thus the viscosity increases. This paper focuses on the modeling of the post condensation process to define the aging state of polyamide 12 powder in laser melting process. Therefore the rheological behavior of PA 12 powder in dependency of time and temperature is investigated. Isothermal viscosity measurements are conducted in order to describe the post condensation reaction with a model. With knowledge of the kinetics of the post condensation reaction the state of aging can be predicted in a second step. Thus expected useful life of the powder can be calculated in dependency of the building chamber temperature. These results are then compared with viscosity values of defined aged PA 12 powder to validate the determined model.

  13. Testing seismic hazard models with Be-10 exposure ages for precariously balanced rocks

    NASA Astrophysics Data System (ADS)

    Rood, D. H.; Anooshehpoor, R.; Balco, G.; Brune, J.; Brune, R.; Ludwig, L. Grant; Kendrick, K.; Purvance, M.; Saleeby, I.

    2012-04-01

    Currently, the only empirical tool available to test maximum earthquake ground motions spanning timescales of 10 ky-1 My is the use of fragile geologic features, including precariously balanced rocks (PBRs). The ages of PBRs together with their areal distribution and mechanical stability ("fragility") constrain probabilistic seismic hazard analysis (PSHA) over long timescales; pertinent applications include the USGS National Seismic Hazard Maps (NSHM) and tests for ground motion models (e.g., Cybershake). Until recently, age constraints for PBRs were limited to varnish microlamination (VML) dating techniques and sparse cosmogenic nuclide data; however, VML methods yield minimum limiting ages for individual rock surfaces, and the interpretations of cosmogenic nuclide data were ambiguous because they did not account for the exhumation history of the PBRs or the complex shielding of cosmic rays. We have recently published a robust method for the exposure dating of PBRs combining Be-10 profiles, a numerical model, and a three-dimensional model for each PBR constructed using photogrammetry (Balco et al., 2011, Quaternary Geochronology). Here, we use this method to calculate new exposure ages and fragilities for 6 PBRs in southern California (USA) near the San Andreas, San Jacinto, and Elsinore faults at the Lovejoy Buttes, Round Top, Pacifico, Beaumont South, Perris, and Benton Road sites (in addition to the recently published age of 18.7 +/- 2.8 ka for a PBR at the Grass Valley site). We combine our ages and fragilities for each PBR, and use these data to test the USGS 2008 NSHM PGA with 2% in 50 year probability, USGS 2008 PSHA deaggregations, and basic hazard curves from USGS 2002 NSHM data.

  14. Testing seismic hazard models with Be-10 exposure ages for precariously balanced rocks

    NASA Astrophysics Data System (ADS)

    Rood, D. H.; Anooshehpoor, R.; Balco, G.; Biasi, G. P.; Brune, J. N.; Brune, R.; Grant Ludwig, L.; Kendrick, K. J.; Purvance, M.; Saleeby, I.

    2012-12-01

    Currently, the only empirical tool available to test maximum earthquake ground motions spanning timescales of 10 ky-1 My is the use of fragile geologic features, including precariously balanced rocks (PBRs). The ages of PBRs together with their areal distribution and mechanical stability ("fragility") constrain probabilistic seismic hazard analysis (PSHA) over long timescales; pertinent applications include the USGS National Seismic Hazard Maps (NSHM) and tests for ground motion models (e.g., Cybershake). Until recently, age constraints for PBRs were limited to varnish microlamination (VML) dating techniques and sparse cosmogenic nuclide data; however, VML methods yield minimum limiting ages for individual rock surfaces, and the interpretations of cosmogenic nuclide data were ambiguous because they did not account for the exhumation history of the PBRs or the complex shielding of cosmic rays. We have recently published a robust method for the exposure dating of PBRs combining Be-10 profiles, a numerical model, and a three-dimensional shape model for each PBR constructed using photogrammetry (Balco et al., 2011, Quaternary Geochronology). Here, we use our published method to calculate new exposure ages for PBRs at 6 sites in southern California near the San Andreas, San Jacinto, and Elsinore faults, including: Lovejoy Buttes (9 +/- 1 ka), Round Top (35 +/- 1 ka), Pacifico (19 +/- 1 ka, but with a poor fit to data), Beaumont South (17 +/- 2 ka), Perris (24 +/- 2 ka), and Benton Road (40 +/- 1 ka), in addition to the recently published age of 18.5 +/- 2.0 ka for a PBR at the Grass Valley site. We combine our ages and fragilities for each PBR, and use these data to test the USGS 2008 NSHM PGA with 2% in 50 year probability, USGS 2008 PSHA deaggregations, and basic hazard curves from USGS 2002 NSHM data. Precariously balanced rock in southern California

  15. Comprehensive stellar population models and the disentanglement of age and metallicity effects

    NASA Technical Reports Server (NTRS)

    Worthey, Guy

    1994-01-01

    The construction of detailed models for intermediate and old stellar populations is described. Input parameters include metallicity (-2 less than (Fe/H) less than 0.5), single-burst age (between 1.5 and 17 Gyr), and initial mass function (IMF) exponent. Quantities output include broadband magnitudes, spectral energy distributions, surface brightness fluctuation magnitudes, and a suite of 21 absorption feature indices. The models are checked against a wide variety of available observations. Examinations of model output yield the following conclusions. (1) If the percentage change delta age/delta Z approximately equals 3/2 for two populations, they will appear almost identical in most indices. A few indices break this degeneracy by being either more abundance sensitive (Fe4668, Fe5015, Fe5709, and Fe5782) or more age sensitive (G4300, H beta, and presumably higher order Balmer lines) than usual. (2) Present uncertainties in stellar evolution are of the same magnitude as the effects of IMF and Y in the indices studied. (3) Changes in abundance ratios (like (Mg/Fe)) are predicted to be readily apparent in the spectra of old stellar populations. (4) The I-band flux of a stellar population is predicted to be nearly independent of metallicity and only modestly sensitive to age. The I band is therefore recommended for standard candle work or studies of M/L in galaxies. Other conclusions stem from this work. (1) Intercomparison of models and observations of two TiO indices seem to indicate variation of the (V/Ti) ratio among galaxies, but it is not clear how this observation ties into the standard picture of chemical enrichment. (2) Current estimates of (Fe/H) for the most metal-rich globulars that are based on integrated indices are probably slightly too high. (3) Colors of population models from different authors exhibit a substantial range. At solar metallicity and 13 Gyr, this range corresponds to an age error of roughly +/- 7 Gyr. Model colors from different authors

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

    PubMed

    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

  17. Basis for the ICRP`s age-specific biokinetic model for uranium

    SciTech Connect

    Leggett, R.W.

    1994-12-01

    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.

  18. Ice-age simulations with a caving ice-sheet model

    SciTech Connect

    Pollard, D.

    1982-01-01

    Further extensions and results of a simple northern hemispheric ice-sheet model are described for the Quaternary ice ages. The basic model predicts ice thickness and bedrock deformation in a north-south cross section, with a prescribed snow-budget distribution shifted uniformly in space to represent the orbital perturbations. An ice calving parameterization crudely representing proglacial lakes or marine incursions can attack the ice whenever the tip drops below sea level. As in Pollard (1982a) the basic model produces a large approx. 100,000-yr response and agrees fairly well with the delta/sup 18/O deep-sea core records. Three extensions of the model are described: an alternative treatment of bedrock deformation, a more realistic ice-shelf model of ice calving, and a generalized parameterization for such features as the North Atlantic deglacial meltwater layer. Much the same ice-age simulations and agreement with the delta/sup 18/O records as with the original model are still obtained. The observed phase-correlation between the 100,000-yr cycles and eccentricity is examined. First, the model is shown to give a approx. 100,000-yr response to nearly any kind of higher-frequency forcing. Although over the last two million years the model phase is mainly controlled by the precessional modulation due to eccentricity, over just the last 600,000-yr the observed phase can also be simulated with eccentricity held constant. A definitive conclusion on the phase-control of the Quaternary ice ages is prevented by uncertainty in the deep-sea core time scales before approx. 600,000-yr B.P. In an appendix the model is applied to West Antarctica where unforced internal oscillations occur with periods of about 50,000-yr.

  19. Impairments of Synaptic Plasticity in Aged Animals and in Animal Models of Alzheimer's Disease

    PubMed Central

    Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia

    2012-01-01

    Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439

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

    PubMed

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

    2013-01-21

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

  1. Scaling and universality in the aging kinetics of the two-dimensional clock model.

    PubMed

    Corberi, Federico; Lippiello, Eugenio; Zannetti, Marco

    2006-10-01

    We study numerically the aging dynamics of the two-dimensional p -state clock model after a quench from an infinite temperature to the ferromagnetic phase or to the Kosterlitz-Thouless phase. The system exhibits the general scaling behavior characteristic of nondisordered coarsening systems. For quenches to the ferromagnetic phase, the value of the dynamical exponents suggests that the model belongs to the Ising-type universality class. Specifically, for the integrated response function chi(t,s) approximately or = s(-a)chif(t/s), we find a(chi) consistent with the value a(chi)=0.28 found in the two-dimensional Ising model.

  2. Effects of Count Area Size on Model Ages Derived from Random CSFDs

    NASA Astrophysics Data System (ADS)

    van der Bogert, Carolyn; Michael, Gregory; Kneissl, Thomas; Hiesinger, Harald; Hendrik Pasckert, Jan

    2015-04-01

    As higher resolution imagery becomes available, smaller regions can be studied. These small areas, however, contain fewer craters for crater size-frequency distribution (CSFD) analysis. For example, a study of irregular mare patches (IMPs) on the Moon [1] could only measure craters, at three IMPs, that were large enough for derivation of absolute model ages (AMAs), using the current lunar chronology and production functions (CF/PF, valid for craters 10mages of IMPs have significant implications for lunar evolution, the robustness of the AMAs is important. In addition, young craters used to define the lunar chronology (e.g., North Ray [3] and Cone [4] craters) have small count areas of less than 1 km^2. While, Hiesinger et al. [3] show that ages derived from small areas are consistent with ages of larger areas, they exhibit variability greater than the statistical error bars [3,4]. Pasckert et al. [5] investigated whether 25 4 km2 count areas within a 100 km2 count area on mare basalt in Tsiolkovsky crater reproduce the age of the larger area. While 19 of the ages are within the error bars of the large area, six of the ages are not. However, the disparate ages could reflect local resurfacing events associated with later volcanism or impact cratering [5]. To eliminate the effects of local geologic activity such that we can evaluate the effects of count area size alone on the robustness of AMAs, we generated random crater distributions for theoretical lunar surfaces with ages of 0.1-4 Ga. We then analyzed the effects of decreasing count area size on the resulting AMAs. The precision of AMAs is determined by the Poisson cratering process and the non-linearity of the CF for the crater measurements themselves [6]. Smaller count areas have fewer craters, such that this statistical precision decreases. However, our study also shows that the accuracy of the AMAs is decreased for smaller count areas. For example, 4 km2 areas on 0.1 Ga

  3. From CIE 2006 physiological model to improved age-dependent and average colorimetric observers.

    PubMed

    Sarkar, Abhijit; Autrusseau, Florent; Viénot, Françoise; Le Callet, Patrick; Blondé, Laurent

    2011-10-01

    In the context of color perception on modern wide-gamut displays with narrowband spectral primaries, we performed a theoretical analysis on various aspects of physiological observers proposed by CIE TC 1-36 (CIEPO06). We allowed certain physiological factors to vary, which was not considered in the CIEPO06 framework. For example, we analyzed that the long-wave-sensitive (LWS) or medium-wave-sensitive (MWS) peak wavelength shift in the photopigment absorption spectra, a factor not modeled in CIEPO06, contributed more toward observer variability than some of the factors considered in the model. Further, we compared the color-matching functions derived from the CIEPO06 model and the CIE 10° standard colorimetric observer to the average observer data from three distinct subgroups of Stiles-Burch observers, formed on the basis of observer ages (22-23 years, 27-29 years, and 49-50 years). The errors in predicting the x(λ) and y(λ) color-matching functions of the intragroup average observers in the long-wave range and in the medium-wave range, respectively, were generally more in the case of the CIEPO06 model compared to the 10° standard colorimetric observer and manifested in both spectral and chromaticity space. In contrast, the short-wave-sensitive z₁₀(λ) function of the 10° standard colorimetric observer performed poorly compared to the CIEPO06 model for all three subgroups. Finally, a constrained nonlinear optimization on the CIEPO06 model outputs showed that a peak wavelength shift of photopigment density alone could not improve the model prediction errors at higher wavelengths. As an alternative, two optimized weighting functions for each of the LWS and MWS cone photopigment densities led to significant improvement in the prediction of intra-age-group average data for both the 22-23 year and 49-50 year age groups. We hypothesize that the assumption in the CIEPO06 model that the peak optical density of visual pigments does not vary with age is false and is

  4. Cycle ageing analysis of a LiFePO4/graphite cell with dynamic model validations: Towards realistic lifetime predictions

    NASA Astrophysics Data System (ADS)

    Sarasketa-Zabala, E.; Gandiaga, I.; Martinez-Laserna, E.; Rodriguez-Martinez, L. M.; Villarreal, I.

    2015-02-01

    The present investigation work compares cycling ageing behaviour upon constant operation conditions (static tests) with degradation under non-constant schemes (dynamic tests), through a novel methodology for ageing model dynamic validation. A LFP-based Li-ion cell performance loss is analysed using a DOD and C-rate stress factors Ah-throughput-domain characterisation method, and represented using a semi-empirical model. The proposed stepwise validation approach enables assessing the static ageing tests acceleration factor and systematically improving the ageing model. The result is a simple but comprehensive model. The predictions root-mean-square error, under dynamic cycling operation conditions, is just 1.75%.

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

    PubMed Central

    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

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

    PubMed Central

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

    2016-01-01

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

  7. Dental age assessment on panoramic radiographs in a Swiss population: a validation study of two prediction models

    PubMed Central

    Kiliaridis, Stavros; Combescure, Christophe; Vazquez, Lydia

    2016-01-01

    Objectives: Dental age assessment methods are widely used for age estimation. This study aimed to analyse the accuracy of a meta-analysis method to estimate dental age in Swiss individuals and to detect potential limitations of the method. Precision of repeated tooth staging using Demirjian's classification on maxillary and mandibular teeth was also assessed. Methods: Panoramic radiographs of 50 Swiss white healthy children were analysed. Developing teeth on the left maxilla and mandible and all third permanent molars were staged following Demirjian's classification. Dental age was calculated for each subject, using a random effects model and a fixed effect model, and compared with chronological age. Results: The mean error of the dental age ranged between −3 and +1 months for both the calculation models. Dental age calculated with the fixed effect model overestimated the age of the subjects (average + 0.10 y, ranging from −1.95 y to +2.16 y) compared with their chronological age, whereas the random effects model underestimated the age (average −0.32 y, ranging from −2.24 y to +1.61 y). Conclusions: Demirjian's method allowed a precise repeated staging of maxillary and mandibular developing teeth. For both calculation models, dental age correlated well, on average, with chronological age of Swiss subjects younger than 12 years. The random effects model showed a better accuracy for these subjects than the fixed effect model. However, both models underestimated the chronological age in subjects older than 12 years. PMID:26250402

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

    NASA Astrophysics Data System (ADS)

    Christiansen, A. V.; Auken, E.; Marker, P. A.; Vilhelmsen, T. N.; Foged, N.; Wernberg, T.; Bauer-Gottwein, P.

    2015-12-01

    Regional hydrological models are important tools in water resources management, but prediction uncertainties are often high due to non-uniqueness of the hydrostratigraphical model. This model is often based on borehole lithology only. However, a much better resolution can be obtained from large geophysical datasets covering the entire domain. Using boreholes to link between hydrostratigraphical classes and resistivity is efficient and emphasizes the need for an all-inclusive data interpretation procedure that can be integrated in groundwater model calibration. We present an automatic method 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 is calibrated against observed lithological data. In other words, the translator function interprets the geophysical resistivities into a 3D clay fraction model and the 3D clay fraction model is then turned into a zonation for the hydrological model by a K-means clustering. We present the methodology by show-casing a study from Denmark were a regional groundwater model is constructed by including lithological information from 3100 boreholes over an 710 sqkm area. The geophysical models spans more than 30 years of data collection and includes approx. 225,000 DC models, and 35,000 EM models, airborne as well as groundbased. The final model was calibrated giving parameters that were comparable with existing models based on thorough and time-consuming manual

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

    PubMed

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

    2017-01-09

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

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

    PubMed

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

    2016-09-30

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

  11. Estimating risks of heat strain by age and sex: a population-level simulation model.

    PubMed

    Glass, Kathryn; Tait, Peter W; Hanna, Elizabeth G; Dear, Keith

    2015-05-18

    Individuals living in hot climates face health risks from hyperthermia due to excessive heat. Heat strain is influenced by weather exposure and by individual characteristics such as age, sex, body size, and occupation. To explore the population-level drivers of heat strain, we developed a simulation model that scales up individual risks of heat storage (estimated using Myrup and Morgan's man model "MANMO") to a large population. Using Australian weather data, we identify high-risk weather conditions together with individual characteristics that increase the risk of heat stress under these conditions. The model identifies elevated risks in children and the elderly, with females aged 75 and older those most likely to experience heat strain. Risk of heat strain in males does not increase as rapidly with age, but is greatest on hot days with high solar radiation. Although cloudy days are less dangerous for the wider population, older women still have an elevated risk of heat strain on hot cloudy days or when indoors during high temperatures. Simulation models provide a valuable method for exploring population level risks of heat strain, and a tool for evaluating public health and other government policy interventions.

  12. Modeling the Multiday Evolution and Aging of Secondary Organic Aerosol During MILAGRO 2006

    SciTech Connect

    Dzepina, K.; Cappa, Christopher D.; Volkamer, Rainer M.; Madronich, Sasha; DeCarlo, Peter; Zaveri, Rahul A.; Jimenez, Jose L.

    2011-03-22

    In this study we apply several recently-proposed models to the evolution of secondary organic aerosols (SOA) and organic gases advected from downtown Mexico City at an altitude of ~3.5 km during three days of aging. We constrain the model with and compare its results to available observations. The model SOA formed from oxidation of volatile organic compounds (V-SOA) when using the aromatic SOA parameterization of Ng et al. (2007) cannot explain the observed SOA concentrations in aged pollution, even as the low-NOx channel becomes more important away from the city. However, when using the aromatic SOA parameterization of Tsimpidi et al. (2010), V-SOA alone is similar to the regional aircraft observations, highlighting the wide diversity in current V-SOA formulations. When the SOA formed from oxidation of both semivolatile and intermediate volatility organic vapors (SI-SOA) is computed following Robinson et al. (2007) the model matches the observed SOA mass, but its O/C is too low by a factor of 2. With the parameterization of Grieshop et al. (2009) the total SOA mass is overpredicted by a factor of ~2 but O/C and volatility are closer to the observations. Heating or dilution of the air results in evaporation of a substantial fraction of the model SOA; this fraction is reduced by aging although differently for heating vs. dilution. Finally, lifting of the airmass tothe free-troposphere during dry convection results in a substantial increase of SOA bycondensation of semivolatile vapors, with this effect being reduced by aging.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    ERIC Educational Resources Information Center

    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…

  15. Towards the modelling of ageing and atherosclerosis effects in ApoE(-/-) mice aortic tissue.

    PubMed

    Waffenschmidt, Tobias; Cilla, Myriam; Sáez, Pablo; Pérez, Marta M; Martínez, Miguel A; Menzel, Andreas; Peña, Estefanía

    2016-08-16

    The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age.

  16. A Computational Model of Inferior Colliculus Responses to Amplitude Modulated Sounds in Young and Aged Rats

    PubMed Central

    Rabang, Cal F.; Parthasarathy, Aravindakshan; Venkataraman, Yamini; Fisher, Zachery L.; Gardner, Stephanie M.; Bartlett, Edward L.

    2012-01-01

    The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated tone or noise carriers at 20–40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function tuning shape. Their temporal modulation transfer functions were also measured. These spike patterns provided experimental measures of rate, vector strength, and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response sub-types were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with age. PMID:23129994

  17. Relating structural and functional anomalous connectivity in the aging brain via neural mass modeling.

    PubMed

    Pons, A J; Cantero, Jose L; Atienza, Mercedes; Garcia-Ojalvo, Jordi

    2010-09-01

    The structural changes that arise as the brain ages influence its functionality. In many cases, the anatomical degradation simply leads to normal aging. In others, the neurodegeneration is large enough to cause neurological disorders (e.g. Alzheimer's disease). Structure and function can be both currently measured using noninvasive techniques, such as magnetic resonance imaging (MRI) and electroencephalography (EEG) respectively. However, a full theoretical scheme linking structural and functional degradation is still lacking. Here we present a neural mass model that aims to bridge both levels of description and that reproduces experimentally observed multichannel EEG recordings of alpha rhythm in young subjects, healthy elderly subjects, and patients with mild cognitive impairment. We focus our attention in the dominant frequency of the signals at different electrodes and in the correlation between specific electrode pairs, measured via the phase-lag index. Our model allows us to study the influence of different structural connectivity pathways, independently of each other, on the normal and aberrantly aging brain. In particular, we study in detail the effect of the thalamic input on specific cortical regions, the long-range connectivity between cortical regions, and the short-range coupling within the same cortical area. Once the influence of each type of connectivity is determined, we characterize the regions of parameter space compatible with the EEG recordings of the populations under study. Our results show that the different types of connectivity must be fine-tuned to maintain the brain in a healthy functioning state independently of its age and brain condition.

  18. Modelling galactic conformity with the colour-halo age relation in the Illustris simulation

    NASA Astrophysics Data System (ADS)

    Bray, Aaron D.; Pillepich, Annalisa; Sales, Laura V.; Zhu, Emily; Genel, Shy; Rodriguez-Gomez, Vicente; Torrey, Paul; Nelson, Dylan; Vogelsberger, Mark; Springel, Volker; Eisenstein, Daniel J.; Hernquist, Lars

    2016-01-01

    Comparisons between observational surveys and galaxy formation models find that dark matter haloes' mass can largely explain their galaxies' stellar mass. However, it remains uncertain whether additional environmental variables, known as assembly bias, are necessary to explain other galaxy properties. We use the Illustris simulation to investigate the role of assembly bias in producing galactic conformity by considering 18 000 galaxies with Mstellar > 2 × 109 M⊙. We find a significant signal of galactic conformity: out to distances of about 10 Mpc, the mean red fraction of galaxies around redder galaxies is higher than around bluer galaxies at fixed stellar mass. Dark matter haloes exhibit an analogous conformity signal, in which the fraction of haloes formed at earlier times (old haloes) is higher around old haloes than around younger ones at fixed halo mass. A plausible interpretation of galactic conformity is the combination of the halo conformity signal with the galaxy colour-halo age relation: at fixed stellar mass, particularly towards the low-mass end, Illustris' galaxy colours correlate with halo age, with the reddest galaxies (often satellites) preferentially found in the oldest haloes. We explain the galactic conformity effect with a simple semi-empirical model, assigning stellar mass via halo mass (abundance matching) and galaxy colour via halo age (age matching). Regarding comparison to observations, we conclude that the adopted selection/isolation criteria, projection effects, and stacking techniques can have a significant impact on the measured amplitude of the conformity signal.

  19. Age-dependent phenotypic characteristics of a triple transgenic mouse model of Alzheimer disease.

    PubMed

    Pietropaolo, Susanna; Feldon, Joram; Yee, Benjamin K

    2008-08-01

    The triple-transgenic mouse line (3 x Tg-AD) harboring PS1M146V, APPSwe, and taup301L transgenes represents the only transgenic model for Alzheimer's disease (AD) to date capturing both beta-amyloid and tau neuropathology. The present study provides an extensive behavioral characterization of the 3 x Tg-AD mouse line, evaluating the emergence of noncognitive and cognitive AD-like symptoms at two ages corresponding to the early (6-7 months) and advanced (12-13 months) stages of AD-pathology. Enhanced responsiveness to aversive stimulation was detected in mutant mice at both ages: the 3 x Tg-AD genotype enhanced acoustic startle response and facilitated performance in the cued-version of the water maze. These noncognitive phenotypes were accompanied by hyperactivity and reduced locomotor habituation in the open field at the older age. Signs of cognitive aberrations were also detected at both ages, but they were limited to associative learning. The present study suggests that this popular transgenic mouse model of AD has clear phenotypes beyond the cognitive domain, and their potential relationship to the cognitive phenotypes should be further explored.

  20. Adult age differences in interference from a prospective-memory task: a diffusion model analysis.

    PubMed

    Horn, Sebastian S; Bayen, Ute J; Smith, Rebekah E

    2013-12-01

    People often slow down their ongoing activities when they must remember an intended action, known as the cost or interference effect of prospective memory (PM). Only a few studies have examined adult age differences in PM interference, and the specific reasons underlying such differences are not well understood. The authors used a model-based approach to reveal processes underlying PM interference and age differences in these processes. Older and younger adults first performed a block of an ongoing lexical decision task alone. An embedded event-based PM task was added in a second block. Simultaneously accounting for the changes in response time distributions and error rates induced by the PM task, Ratcliff's (Psychological Review 85:59-108, 1978) diffusion model was used to decompose the nonlinear combination of speed and accuracy into psychologically meaningful components. Remembering an intention not only reduced processing efficiency in both age groups, but also prolonged peripheral nondecision times and induced response cautiousness. Overall, the findings suggest that there are multiple, but qualitatively similar factors underlying PM task interference in both age groups.

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

    PubMed

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

    2014-01-01

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

  2. Spectroscopic age and metallicity for a sample of Globular Clusters from Stellar Population Models

    NASA Astrophysics Data System (ADS)

    Stock, M. J.; Calderón, P.

    2009-05-01

    We present spectroscopic age and metallicity predictions for a sample of 20 Globular Clusters in the massive E0 galaxy NGC 1407 (data from Cenarro et al. 2007, AJ, 134, 391) and for the Galacic Globular Clusters data from the Library of Integrated Spectra of Galactic Globular Clusters (GGC's) from Schiavon et al. (2005, ApJS, 160, 163) including the widely studied 47 Tuc cluster. Using index-index plots we compared model Single Stellar Populations (SSP's) spectra to the integrated spectra of both samples of Globular Clusters using high resolution line strength indices (Stock, in prep.) and the syntethic SSP's models from P. Coelho (2007, private comm.) as well as the CB07 solar models. For the GC's in NGC1407, the predictions from the syntethic models's with [α /Fe]=0.4 are in good agreement with the results from Cenarro et al. (2007, AJ, 134, 391), taking into account that the dispersion is partially due to the fact that the mean [α/Fe] ratio of the sample is ≈ 0.3 dex, resulting in younger ages and lower metallicities (Thomas et al. 2003, A&A, 401, 429). We observe a bimodal distribution of the Fe4383+ index which is in turn an indicator of metallicity, also seen in Cenarro et al. (2005). The CB07 models predict ages that are widely spread over the plot yielding ages greater than 14 Gyrs. The metallicity derived from these models are very low for almost all the objects (Z < 0.008). The distribution of the GGC's on the syntethic model grid shows a trend in the sense that metal poor clusters are younger than metal rich ones, but this effect might not be real (de Angeli et al. 2005, AJ, 130, 116). For 47 Tuc we estimate an age of ≈ 10 Gyr, and metallicity Z < 0.011 (<[Fe/H]= -0.5) which are both comparable with the values reported in the literature (Carretta et al. 2000; Liu & Chaboyer 2000, ApJ, 544, 818; Schiavon et al. 2002, ApJ, 580, 873; Gratton et al. 2003, A&A, 408, 529).

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  4. Cryptococcus neoformans constitutes an ideal model organism to unravel the contribution of cellular aging to the virulence of chronic infections.

    PubMed

    Bouklas, Tejas; Fries, Bettina C

    2013-08-01

    Aging affects all organisms, from unicellular yeasts to multicellular humans. Studies in model organisms demonstrate that the pathways that mediate the two forms of aging, replicative and chronological, are highly conserved. Most studies are focused on the effect of aging on an individual cell rather than a whole population. Complex longevity regulation, however, makes aging a highly adaptive trait that is subject to natural selection. Recent studies have shed light on the potential relevance of aging in fungal pathogens, which undergo replicative aging when they expand in the host environment. Hence, pathogens causing chronic infections can constitute ideal model organisms in unraveling the contribution of selection to aging within a population and help elucidate the contribution of aging itself to the virulence of infections.

  5. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

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

    PubMed

    Rock, K S; Wood, D A; Keeling, M J

    2015-09-01

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

  7. EFFECTS OF AGE, DIETARY AND BEHAVIORAL ENRICHMENT ON BRAIN MITOCHONDRIA IN A CANINE MODEL OF HUMAN AGING

    PubMed Central

    Head, E.; Nukala, V. N.; Fenoglio, K.A.; Muggenburg, B. A.; Cotman, C. W.; Sullivan, P. G.

    2009-01-01

    Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with behavioral enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (Vitamins E, C, fruits and vegetables) and mitochondrial co-factors (lipoic acid and carnitine). Behavioral enrichment consisted of physical exercise, social enrichment and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast behavioral enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by behavioral enrichment. PMID:19703441

  8. A proposed theoretical model to explain relative age effects in sport.

    PubMed

    Hancock, David J; Adler, Ashley L; Côté, Jean

    2013-01-01

    Exemplary scientific methods describe concepts and provide theories for further testing. For the field of relative age effects (RAEs) in sport, the scientific method appears to be limited to description. The purpose of this paper is to provide a theoretical model to explain RAEs in sport, which researchers can use to test the effects, as well as to generate new hypotheses and recommendations. Herein, we argue that social agents have the largest influence on RAEs. Specifically, we propose that parents influence RAEs through Matthew effects, coaches influence RAEs through Pygmalion effects and athletes influence RAEs through Galatea effects. Integrating these three theories, we propose a model that explains RAEs through these various social agents. This paper provides a theoretical foundation from which researchers can further understand, explain and eventually use to create policies aimed at limiting the negative effect of relative age in sport.

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

    PubMed

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

    2015-04-24

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

  10. An observer for a nonlinear age-structured model of a harvested fish population.

    PubMed

    Ngom, Diène; Iggidr, Abderrahman; Guiro, Aboudramane; Ouahbi, Abderrahim

    2008-04-01

    We consider an age-structured model of a harvested population. This model is a discrete-time system that includes a nonlinear stock-recruitment relationship. Our purpose is to estimate the stock state. To achieve this goal, we built an observer, which is an auxiliary system that uses the total number of fish caught over each season and gives a dynamical estimation of the number of fish by age class. We analyse the convergence of the observer and we show that the error estimation tends to zero with exponential speed if a condition on the fishing effort is satisfied. Moreover the constructed observer (dynamical estimator) does not depend on the poorly understood stock-recruitment relationship. This study shows how some tools from nonlinear control theory can help to deal with the state estimation problem in the field of renewable resource management.

  11. From chaos to chaos. An analysis of a discrete age-structured prey-predator model.

    PubMed

    Wikan, A

    2001-12-01

    Discrete age-structured density-dependent one-population models and discrete age-structured density-dependent prey-predator models are considered. Regarding the former, we present formal proofs of the nature of bifurcations involved as well as presenting some new results about the dynamics in unstable and chaotic parameter regions. Regarding the latter, we show that increased predation may act both as a stabilizing and a destabilizing effect. Moreover, we find that possible periodic dynamics of low period, either exact or approximate, may not be generated by the predator, but it may be generated by the prey. Finally, what is most interesting from the biological point of view, is that given that the prey, in absence of the predator, exhibits periodic or almost periodic oscillations of low period, then the introduction of the predator does not alter this periodicity in any substantial way until the stabilizing effect of increased predation becomes so strong that a stable equilibrium is achieved.

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

    PubMed Central

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

    2015-01-01

    The Late Pliocene epoch is a potential analogue for future climate in a warming world. Here we reconstruct Plio-Pleistocene East Antarctic Ice Sheet (EAIS) variability using cosmogenic nuclide exposure ages and model simulations to better understand ice sheet behaviour under such warm conditions. New and previously published exposure ages indicate interior-thickening during the Pliocene. An ice sheet model with mid-Pliocene boundary conditions also results in interior thickening and suggests that both the Wilkes Subglacial and Aurora Basins largely melted, offsetting increased ice volume. Considering contributions from West Antarctica and Greenland, this is consistent with the most recent IPCC AR5 estimate, which indicates that the Pliocene sea level likely did not exceed +20 m on Milankovitch timescales. The inception of colder climate since ∼3 Myr has increased the sea ice cover and inhibited active moisture transport to Antarctica, resulting in reduced ice sheet thickness, at least in coastal areas. PMID:25908601

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  15. Optimal Harvesting in an Age-Structured Predator-Prey Model

    SciTech Connect

    Fister, K. Renee Lenhart, Suzanne

    2006-06-15

    We investigate optimal harvesting control in a predator-prey model in which the prey population is represented by a first-order partial differential equation with age-structure and the predator population is represented by an ordinary differential equation in time. The controls are the proportions of the populations to be harvested, and the objective functional represents the profit from harvesting. The existence and uniqueness of the optimal control pair are established.

  16. Cohesive finite element modeling of age-related toughness loss in human cortical bone.

    PubMed

    Ural, Ani; Vashishth, Deepak

    2006-01-01

    Although the age-related loss of bone quality has been implicated in bone fragility, a mechanistic understanding of the relationship is necessary for developing diagnostic and treatment modalities in the elderly population at risk of fracture. In this study, a finite element based cohesive zone model is developed and applied to human cortical bone in order to capture the experimentally shown rising crack growth behavior and age-related loss of bone toughness. The cohesive model developed here is based on a traction-crack opening displacement relationship representing the fracture processes in the vicinity of a propagating crack. The traction-displacement curve, defining the cohesive model, is composed of ascending and descending branches that incorporate material softening and nonlinearity. The results obtained indicate that, in contrast to initiation toughness, the finite element simulations of crack growth in compact tension (CT) specimens successfully capture the rising R-curve (propagation toughness) behavior and the age-related loss of bone toughness. In close correspondence with the experimentally observed decrease of 14-15% per decade, the finite element simulation results show a decrease of 13% in the R-curve slope per decade. The success of the simulations is a result of the ability of cohesive models to capture and predict the parameters related to bone fracture by representing the physical processes occurring in the vicinity of a propagating crack. These results illustrate that fracture mechanisms in the process zone control bone toughness and any modification to these would cause age-related toughness loss.

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

    PubMed

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

    2016-06-01

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

  18. Protein and DNA oxidation in different anatomic regions of rat brain in a mimetic ageing model.

    PubMed

    Yanar, Karolin; Aydın, Seval; Cakatay, Ufuk; Mengi, Murat; Buyukpınarbaşılı, Nur; Atukeren, Pınar; Sitar, Mustafa E; Sönmez, Aslı; Uslu, Ezel

    2011-12-01

    It has been reported that d-galactose administration causes an increase in oxidative and osmotic stresses in several tissues of rodents. In this study, we established a brain ageing model by using d-galactose and investigated the concentrations of oxidative stress markers on the hippocampus, parietal and frontal lobes of male Sprague-Dawley rats. A mimetic ageing model was established by injecting d-galactose (60 mg/kg/day/i.p.) in the experimental group for 42 days. At the end of this period, we tested spatial memory using the Morris water maze test. To investigate the magnitude of oxidative damage in proteins, lipids and DNA, we studied the concentrations of various oxidative stress parameters in the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell oxidative damage was observed in each of the three anatomic regions. It was found that protein carbonyl groups and advanced oxidation product concentrations in the d-galactose applied group were significantly high in each of the three brain lobes compared with the control group. Thiol concentration was found to be decreased in the parietal lobe. A concurrent increase in lipid hydroperoxides was also observed in this lobe. On the other hand, 8-hydroxy-2'-deoxyguanosine concentration was significantly increased in the hippocampal lobe of rats in the experimental group when compared with the controls. The results obtained from the mimetic ageing model rats showed that various anatomical regions of brain have different susceptibility to oxidative damage of proteins, lipids and DNA.

  19. Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

    PubMed

    Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

    2014-11-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

  20. Monitoring and Modeling the Fluctuations in Apparent Groundwater Age During a 30-Day Pumping Test.

    NASA Astrophysics Data System (ADS)

    Perle, M. E.; Zhang, Y.; Fogg, G. E.

    2004-12-01

    Recent research shows that dispersion due to geologic heterogeneity can cause large (10's to 100's of yrs) variations in actual groundwater age within individual samples drawn from a well, even if well bore mixing is not significant. We hypothesize that the presence of such large ranges in groundwater age may cause the mean apparent age as estimated from environmental tracers such as CFC's, SF&_{6}, and ^{3}H-^{3}He to drift measurably during long-term, continuous pumping. This hypothesis was confirmed by 3-D numerical experiments wherein variation in groundwater ages under high-rate (\\sim0.06 m^{3}/s; 1,000 gpm) long-term pumping was modeled using backward-time random walk particle tracking techniques combined with geostatistical simulations of hydrofacies heterogeneity. Results indicate that the age distribution within a water sample and the mean apparent age implied by environmental tracers is strongly influenced by historical atmospheric concentrations of environmental tracers and subsurface heterogeneity. As a partial implementation of this same experiment in the field, an abandoned well was pumped at a low rate (\\sim0.005 m^{3}/s; 75 gpm) during 53 days. Water samples were collected from the top and bottom of a 25 foot well screen at 12 hour intervals for the first 30 days and were analyzed for CFC's, SF&6, and 3H-3He. The measured tracer ages indicate that 1) CFC-11 apparent ages increased with time within the first five days of pumping and then remained constant for the remainder of the pump test; 2) trends in CFC-12, CFC-113 and SF&_{6}$ indicate a discrepancy in apparent ages with CFC-11, 3) water reaching the top interval is younger than water reaching the bottom interval. Gas samples were collected from the unsaturated zone to investigate possible CFC contamination and tracer concentration spatial variations in the pumping well recharge zone. Potential effects of heterogeneity and local CFC contamination on the monitoring results will be discussed.

  1. Does age play a role in the structure of anxiety and depression in children and youths? An investigation of the tripartite model in three age cohorts.

    PubMed

    Turner, Cynthia M; Barrett, Paula M

    2003-08-01

    Although previous studies provide some support for a tripartite model of relations between anxiety and depression in children there is evidence to suggest that anxiety and depression may be increasingly differentiated over development. Using a confirmatory factor analytic strategy with rationally selected item sets from the Revised Children's Manifest Anxiety Scale and the Children's Depression Inventory, the current study sought to test unitary, dual, and tripartite models for anxiety and depression in a cross-sectional design using 3 narrow-band age cohorts of nonreferred children and youths. The results found little evidence of increasing differentiation. All models provided a moderate fit to the data, with some evidence that a correlated 3-factor model was the preferred model in all age cohorts. Further research is required to explore the discriminant validity and clinical utility of the tripartite dimensions in childhood populations.

  2. Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age.

    PubMed

    Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

    2015-11-01

    To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18-39, 40-64, 65 +  years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of -0.03 to 0.01 METs, bias percent of -0.8 to 0.3%, and a rMSE range of 0.81-1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed.

  3. Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age

    PubMed Central

    Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

    2016-01-01

    To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18–39, 40–64, 65 + years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of −0.03 to 0.01 METs, bias percent of −0.8 to 0.3%, and a rMSE range of 0.81–1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed. PMID:26449155

  4. [Utilization of Werner syndrome mouse model in studying premature aging and tumor].

    PubMed

    Jia, Shu-Ting; Yang, Shi-Hua; Luo, Ying

    2009-08-01

    Werner syndrome (WS) is a rare autosomal recessive genetic disease in human. It is considered as a good model disease in studying human premature syndrome. Werner protein (WRN) is a nuclear protein mutated in WS. Recent biochemical and genetic studies indicated that WRN plays important roles in DNA replication, DNA repair, and telomere maintenance. Here, we reviewed the molecular genetics of WS and the importance of telomere and WRN in the development of WS. Knocking out both telomerase and Wrn genes in mouse faithfully manifests human WS. The mouse model provides a unique genetic platform to explore the crosstalk of premature aging and tumor.

  5. AGING MODEL FOR CANE FIBERBOARD OVERPACK IN THE 9975 SHIPPING PACKAGE

    SciTech Connect

    Daugherty, W.; Harris, S.

    2010-03-05

    Many radioactive material shipping packages incorporate a cane fiberboard overpack for thermal insulation and impact resistance. Mechanical, thermal and physical properties have been measured on cane fiberboard following thermal aging in several temperature/humidity environments. Several of the measured properties change significantly over time in the more severe environments, while other properties are relatively constant. Changes in each of the properties have been fit to a model to allow predictions of degradation under various storage scenarios. Additional data continue to be collected to provide for future refinements to the model.

  6. Age models for peat deposits on the basis of coupled lead-210 and radiocarbon data.

    NASA Astrophysics Data System (ADS)

    Piotrowska, Natalia; de Vleeschouwer, François; Sikorski, Jarosław; Sensuła, Barbara; Michczyński, Adam; Fiałkiewicz-Kozieł, Barbara; Palowski, Bernard

    2010-05-01

    The study presents three examples of age-model construction based on the results of 210Pb and 14C dating methods applied to peat deposits. The three sites are ombrotrophic peat bogs: the Misten (Belgium), Slowinskie Bloto (N Poland) and Puscizna Mala (S Poland). All sites have been subjected to multiproxy studies aimed at reconstructing paleoenvironment and human activity, covering the last 1500, 1300 and 1800 years, respectively (De Vleeschouwer et al. 2009A, 2009B, in prep., Fialkiewicz-Koziel, ongoing PhD). A detailed comparison between 210Pb and post-bomb 14C results in the Misten bog has also been carried out by Piotrowska et al. (2009). In all cores, the 210Pb activity was calculated using 210Po and 208Po activities after acid-extraction from bulk samples, subsequent deposition on silver discs and measurements by alpha spectrometry. Unsupported 210Pb was detected until 35cm in Slowinskie Bloto, 15cm in the Misten and 19cm in Puscizna Mala. Constant Rate of Supply (CRS) model was then applied to compute ages of each 1-cm core interval. For the Misten and Slowinskie Bloto, radiocarbon measurements were performed on selected aboveground plant macrofossils, mainly Sphagnum spp. or Calluna vulgaris, Erica tetralix, and Andromeda polyfolia. Radiocarbon ages were determined using accelerator mass spectrometry (AMS) after acid-alkali-acid wash, combustion, purification of carbon dioxide and graphitisation. For Puscizna Mala bulk samples were dated after chemical preparation of benzene for liquid scintillation counting (LSC) or CO2 for gas proportional counting (GPC). Radiocarbon calibration was undertaken using the Intcal04 calibration curve and OxCal 4 software. As a priori information the 210Pb-derived ages were used in a P_Sequence model (Bronk Ramsey, 2008). A number of dates characterized by low agreement with stratigraphical order had to be considered as outliers and rejected from the final age model. For building a continuous age models a non-linear approach

  7. Wistar rats: a forgotten model of age-related hearing loss

    PubMed Central

    Alvarado, Juan C.; Fuentes-Santamaría, Verónica; Gabaldón-Ull, María C.; Blanco, José L.; Juiz, José M.

    2014-01-01

    Age-related hearing loss (ARHL) is one of the most frequent sensory impairments in senescence and is a source of important socio-economic consequences. Understanding the pathological responses that occur in the central auditory pathway of patients who suffer from this disability is vital to improve its diagnosis and treatment. Therefore, the goal of this study was to characterize age-related modifications in auditory brainstem responses (ABR) and to determine whether these functional responses might be accompanied by an imbalance between excitation and inhibition in the cochlear nucleus of Wistar rats. To do so, ABR recordings at different frequencies and immunohistochemistry for the vesicular glutamate transporter 1 (VGLUT1) and the vesicular GABA transporter (VGAT) in the ventral cochlear nucleus (VCN) were performed in young, middle-aged and old male Wistar rats. The results demonstrate that there was a significant increase in the auditory thresholds, a significant decrease in the amplitudes and an increase in the latencies of the ABR waves as the age of the rat increased. Additionally, there were decreases in VGLUT1 and VGAT immunostaining in the VCN of older rats compared to younger rats. Therefore, the observed age-related decline in the magnitude of auditory evoked responses might be due in part to a reduction in markers of excitatory function; meanwhile, the concomitant reduction in both excitatory and inhibitory markers might reflect a common central alteration in animal models of ARLH. Together, these findings highlight the suitability of the Wistar rat as an excellent model to study ARHL. PMID:24634657

  8. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.

    PubMed

    Van Dam, Debby; D'Hooge, Rudi; Staufenbiel, Matthias; Van Ginneken, Chris; Van Meir, Frans; De Deyn, Peter P

    2003-01-01

    Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.

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

    PubMed

    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.

  10. Aging into Perceptual Control: A Dynamic Causal Modeling for fMRI Study of Bistable Perception

    PubMed Central

    Dowlati, Ehsan; Adams, Sarah E.; Stiles, Alexandra B.; Moran, Rosalyn J.

    2016-01-01

    Aging is accompanied by stereotyped changes in functional brain activations, for example a cortical shift in activity patterns from posterior to anterior regions is one hallmark revealed by functional magnetic resonance imaging (fMRI) of aging cognition. Whether these neuronal effects of aging could potentially contribute to an amelioration of or resistance to the cognitive symptoms associated with psychopathology remains to be explored. We used a visual illusion paradigm to address whether aging affects the cortical control of perceptual beliefs and biases. Our aim was to understand the effective connectivity associated with volitional control of ambiguous visual stimuli and to test whether greater top-down control of early visual networks emerged with advancing age. Using a bias training paradigm for ambiguous images we found that older participants (n = 16) resisted experimenter-induced visual bias compared to a younger cohort (n = 14) and that this resistance was associated with greater activity in prefrontal and temporal cortices. By applying Dynamic Causal Models for fMRI we uncovered a selective recruitment of top-down connections from the middle temporal to Lingual gyrus (LIN) by the older cohort during the perceptual switch decision following bias training. In contrast, our younger cohort did not exhibit any consistent connectivity effects but instead showed a loss of driving inputs to orbitofrontal sources following training. These findings suggest that perceptual beliefs are more readily controlled by top-down strategies in older adults and introduce age-dependent neural mechanisms that may be important for understanding aberrant belief states associated with psychopathology. PMID:27064235

  11. A prognosis method using age-dependent hidden semi-Markov model for equipment health prediction

    NASA Astrophysics Data System (ADS)

    Peng, Ying; Dong, Ming

    2011-01-01

    Health monitoring and prognostics of equipment is a basic requirement for condition-based maintenance (CBM) in many application domains. This paper presents an age-dependent hidden semi-Markov model (HSMM) based prognosis method to predict equipment health. By using hazard function (h.f.), CBM is based on a failure rate which is a function of both the equipment age and the equipment conditions. The state values of the equipment condition considered in CBM, however, are limited to those stochastically increasing over time and those having non-decreasing effect on the hazard rate. The previous HSMM based prognosis algorithm assumed that the transition probabilities are only state-dependent, which means that the probability of making transition to a less healthy state does not increase with the age. In the proposed method, in order to characterize the deterioration of equipment, three types of aging factors that discount the probabilities of staying at current state while increasing the probabilities of transitions to less healthy states are integrated into the HSMM. With an iteration algorithm, the original transition matrix obtained from the HSMM can be renewed with aging factors. To predict the remaining useful life (RUL) of the equipment, hazard rate is introduced to combine with the health-state transition matrix. With the classification information obtained from the HSMM, which provides the current health state of the equipment, the new RUL computation algorithm could be applied for the equipment prognostics. The performances of the HSMMs with aging factors are compared by using historical data colleted from hydraulic pumps through a case study.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  13. The Role of a Model's Age for Young Children's Imitation: A Research Review

    ERIC Educational Resources Information Center

    Zmyj, Norbert; Seehagen, Sabine

    2013-01-01

    The influence of a model's age on young children's behaviour has been a subject of considerable debate among developmental theorists. Despite the recent surge of interest, controversy remains about the nature of peer influence in early life. This article reviews studies that investigated the influence of a model's age on young…

  14. Models for preclinical studies in aging-related disorders: One is not for all

    PubMed Central

    Santulli, Gaetano; Borras, Consuelo; Bousquet, Jean; Calzà, Laura; Cano, Antonio; Illario, Maddalena; Franceschi, Claudio; Liotta, Giuseppe; Maggio, Marcello; Molloy, William D.; Montuori, Nunzia; O’Caoimh, Rónán; Orfila, Francesc; Rauter, Amelia P.; Santoro, Aurelia; Iaccarino, Guido

    2015-01-01

    Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment–effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical. PMID:27042427

  15. Computer simulation of the coffee leaf miner using sexual Penna aging model

    NASA Astrophysics Data System (ADS)

    de Oliveira, A. C. S.; Martins, S. G. F.; Zacarias, M. S.

    2008-01-01

    Forecast models based on climatic conditions are of great interest in Integrated Pest Management (IPM) programs. The success of these models depends, among other factors, on the knowledge of the temperature effect on the pests’ population dynamics. In this direction, a computer simulation was made for the population dynamics of the coffee leaf miner, L. coffeella, at different temperatures, considering experimental data relative to the pest. The age structure was inserted into the dynamics through sexual Penna Model. The results obtained, such as life expectancy, growth rate and annual generations’ number, in agreement to those in laboratory and field conditions, show that the simulation can be used as a forecast model for controlling L. coffeella.

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

    USGS Publications Warehouse

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

  18. A Ternary Age-Mixing Model to Explain Contaminant Occurrence in a Deep Supply Well

    PubMed Central

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

    2014-01-01

    The age distribution of water from a public-supply well in a deep alluvial aquifer was estimated and used to help explain arsenic variability in the water. The age distribution was computed using a ternary mixing model that combines three lumped parameter models of advection-dispersion transport of environmental tracers, which represent relatively recent recharge (post-1950s) containing volatile organic compounds (VOCs), old intermediate depth groundwater (about 6500 years) that was free of drinking-water contaminants, and very old, deep groundwater (more than 21,000 years) containing arsenic above the USEPA maximum contaminant level of 10 µg/L. The ternary mixing model was calibrated to tritium, chloroflorocarbon-113, and carbon-14 (14C) concentrations that were measured in water samples collected on multiple occasions. Variability in atmospheric 14C over the past 50,000 years was accounted for in the interpretation of 14C as a tracer. Calibrated ternary models indicate the fraction of deep, very old groundwater entering the well varies substantially throughout the year and was highest following long periods of nonoperation or infrequent operation, which occured during the winter season when water demand was low. The fraction of young water entering the well was about 11% during the summer when pumping peaked to meet water demand and about 3% to 6% during the winter months. This paper demonstrates how collection of multiple tracers can be used in combination with simplified models of fluid flow to estimate the age distribution and thus fraction of contaminated groundwater reaching a supply well under different pumping conditions. PMID:24597520

  19. The influence of aging on critical transformation stress levels and martensite start temperatures in NiTi. Part 1: Aged microstructure and micro-mechanical modeling

    SciTech Connect

    Gall, K.; Sehitoglu, H.; Chumlyakov, Y.I.; Kireeva, I.V.; Maier, H.J.

    1999-01-01

    Transmission electron microscopy is used to determine the microstructures of a Ti-50.8 at% Ni alloy given different aging treatments. Two different peak-aging treatments are shown to result in disk shaped semi-coherent Ti{sub 3}Ni{sub 4} precipitates with a diameter ranging from 50 nm to 200 nm depending on the aging temperature. In the peak-aged materials, strong strain fields are clearly visible on TEM micrographs. An Eshelby based model is used to predict the local stress fields due to the differences in the lattice parameters of the precipitates and surrounding matrix. The position dependent local stress fields are then resolved onto the 24 different martensite correspondence variant pairs (CVP`s). It is further demonstrated that due to the unique orientation relationship that exists between the precipitate variants and the martensite CVP`s, the local resolved shear stresses are extremely large on some CVP`s and negligible on others. When the Ni rich NiTi is over-aged, it is found that the precipitates coarsen to approximately 1000 nm, they become in-coherent, and the local stress fields disappear. It is also determined that after over-aging in the average composition of the matrix drops from 50.8 at% Ni to approximately 50.4 at% Ni. In a subsequent paper (part 2) the results here are used to explain the dependence of the critical transformation stress levels and martensite start temperatures on the aging treatment.

  20. Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation

    PubMed Central

    Palko, Joel R.; Morris, Hugh J.; Pan, Xueliang; Harman, Christine D.; Koehl, Kristin L.; Gelatt, Kirk N.; Plummer, Caryn E.; Komáromy, András M.; Liu, Jun

    2016-01-01

    Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in

  1. Time evolution of damage due to environmentally assisted aging in a fiber bundle model

    NASA Astrophysics Data System (ADS)

    Lennartz-Sassinek, S.; Main, I. G.; Danku, Z.; Kun, F.

    2013-09-01

    Damage growth in composite materials is a complex process which is of interest in many fields of science and engineering. We consider this problem in a fiber bundle model where fibers undergo an aging process due to the accumulation of damage driven by the locally acting stress in a chemically active environment. By subjecting the bundle to a constant external load, fibers fail either when the load on them exceeds their individual intrinsic strength or when the accumulated internal damage exceeds a random threshold. We analyze the time evolution of the breaking process under low external loads where aging of fibers dominates. In the mean field limit, we show analytically that the aging system continuously accelerates in a way which can be characterized by an inverse power law of the event rate with a singularity that defines a failure time. The exponent is not universal; it depends on the details of the aging process. For localized load sharing, a more complex damage process emerges which is dominated by distinct spatial regions of the system with different degrees of stress concentration. Analytical calculations revealed that the final acceleration to global failure is preceded by a stationary accumulation of damage. When the disorder is strong, the accelerating phase has the same functional behavior as in the mean field limit. The analytical results are verified by computer simulations.

  2. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Schlitz, Marilyn

    2017-01-01

    Objectives: Understanding and managing the process of aging is a central issue in modern society. This is a critical factor given the demographic shift toward an aging population and the negative stereotypes around aging that can limit people’s worldview on aging with gratitude and well-being. Methods: Building on three decades of qualitative and quantitative studies on positive worldview transformation at the California-based Institute of Noetic Sciences, this article applies an empirically derived naturalistic model of transformation to aging. The Grateful Aging Program is introduced as a set of transformative steps to promote well-being and to shift fear of aging into inspiration for living well. Results: Nine steps to Grateful Aging are identified: 1) answer the call to transformation, 2) cultivate curiosity, 3) formalize a Grateful Aging practice, 4) set intention for Grateful Aging, 5) pay attention to the gifts of aging, 6) build Grateful Aging habits, 7) find guidance, 8) move to acceptance, and 9) transform self and society. Educational programs are described for elderly patients and for the health care professionals who serve them. Conclusion: The Grateful Aging Program is designed to expand awareness of healthy, mindful, and meaningful aging; to promote individual and social well-being; and to facilitate a supportive atmosphere for personal enrichment and shared learning. PMID:28241911

  6. Improved age modelling approaches as exemplified by the revised chronology for the Central European varved lake Soppensee

    NASA Astrophysics Data System (ADS)

    Blockley, S. P. E.; Ramsey, C. Bronk; Lane, C. S.; Lotter, A. F.

    2008-01-01

    One of the key factors in understanding past climate change is the development of robust age models that have sufficient chronological precision for comparing different palaeoclimate archives, while retaining accuracy. Recent developments in Bayesian age modelling are applied here to the Swiss varve lake, Soppensee. We develop revised age models for this sequence using the available stratigraphic information to constrain the calibrated radiocarbon ages. We begin by using stratigraphical order as the only constraint and then sequentially increase the information incorporated into the model, using relative varve age, sample depth, and varying depositional models. Within this Bayesian framework, we develop internally robust models that significantly improve the dating precision and are applicable to both varved and non-varved sequences. We then compare the model output to wider chronological information, such as the age of the Laacher See Tephra in order to test the model accuracy. The results of this exercise suggest that these methods can be used to build very reliable improved age models in a variety of records.

  7. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    PubMed Central

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  8. Splicing-directed therapy in a new mouse model of human accelerated aging.

    PubMed

    Osorio, Fernando G; Navarro, Claire L; Cadiñanos, Juan; López-Mejía, Isabel C; Quirós, Pedro M; Bartoli, Catherine; Rivera, José; Tazi, Jamal; Guzmán, Gabriela; Varela, Ignacio; Depetris, Danielle; de Carlos, Félix; Cobo, Juan; Andrés, Vicente; De Sandre-Giovannoli, Annachiara; Freije, José M P; Lévy, Nicolas; López-Otín, Carlos

    2011-10-26

    Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna splicing, markedly reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide-based therapies for treating human diseases of accelerated aging.

  9. A mathematical model of physiological processes and its application to the study of aging

    NASA Technical Reports Server (NTRS)

    Hibbs, A. R.; Walford, R. L.

    1989-01-01

    The behavior of a physiological system which, after displacement, returns by homeostatic mechanisms to its original condition can be described by a simple differential equation in which the "recovery time" is a parameter. Two such systems, which influence one another, can be linked mathematically by the use of "coupling" or "feedback" coefficients. These concepts are the basis for many mathematical models of physiological behavior, and we describe the general nature of such models. Next, we introduce the concept of a "fatal limit" for the displacement of a physiological system, and show how measures of such limits can be included in mathematical models. We show how the numerical values of such limits depend on the values of other system parameters, i.e., recovery times and coupling coefficients, and suggest ways of measuring all these parameters experimentally, for example by monitoring changes induced by X-irradiation. Next, we discuss age-related changes in these parameters, and show how the parameters of mortality statistics, such as the famous Gompertz parameters, can be derived from experimentally measurable changes. Concepts of onset-of-aging, critical or fatal limits, equilibrium value (homeostasis), recovery times and coupling constants are involved. Illustrations are given using published data from mouse and rat populations. We believe that this method of deriving survival patterns from model that is experimentally testable is unique.

  10. Optimizing a Male Reproductive Aging Mouse Model by d-Galactose Injection

    PubMed Central

    Liao, Chun-Hou; Chen, Bing-Huei; Chiang, Han-Sun; Chen, Chiu-Wei; Chen, Mei-Feng; Ke, Chih-Chun; Wang, Ya-Yun; Lin, Wei-Ning; Wang, Chi-Chung; Lin, Ying-Hung

    2016-01-01

    The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8–10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies

  11. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    PubMed Central

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging. PMID:26078824

  12. Methodology for the Incorporation of Passive Component Aging Modeling into the RAVEN/ RELAP-7 Environment

    SciTech Connect

    Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua; Alfonsi, Andrea; Askin Guler; Tunc Aldemir

    2014-11-01

    Passive system, structure and components (SSCs) will degrade over their operation life and this degradation may cause to reduction in the safety margins of a nuclear power plant. In traditional probabilistic risk assessment (PRA) using the event-tree/fault-tree methodology, passive SSC failure rates are generally based on generic plant failure data and the true state of a specific plant is not reflected realistically. To address aging effects of passive SSCs in the traditional PRA methodology [1] does consider physics based models that account for the operating conditions in the plant, however, [1] does not include effects of surveillance/inspection. This paper represents an overall methodology for the incorporation of aging modeling of passive components into the RAVEN/RELAP-7 environment which provides a framework for performing dynamic PRA. Dynamic PRA allows consideration of both epistemic and aleatory uncertainties (including those associated with maintenance activities) in a consistent phenomenological and probabilistic framework and is often needed when there is complex process/hardware/software/firmware/ human interaction [2]. Dynamic PRA has gained attention recently due to difficulties in the traditional PRA modeling of aging effects of passive components using physics based models and also in the modeling of digital instrumentation and control systems. RAVEN (Reactor Analysis and Virtual control Environment) [3] is a software package under development at the Idaho National Laboratory (INL) as an online control logic driver and post-processing tool. It is coupled to the plant transient code RELAP-7 (Reactor Excursion and Leak Analysis Program) also currently under development at INL [3], as well as RELAP 5 [4]. The overall methodology aims to: • Address multiple aging mechanisms involving large number of components in a computational feasible manner where sequencing of events is conditioned on the physical conditions predicted in a simulation

  13. Modelling the Effects of Ageing Time of Starch on the Enzymatic Activity of Three Amylolytic Enzymes

    PubMed Central

    Guerra, Nelson P.; Pastrana Castro, Lorenzo

    2012-01-01

    The effect of increasing ageing time (t) of starch on the activity of three amylolytic enzymes (Termamyl, San Super, and BAN) was investigated. Although all the enzymatic reactions follow michaelian kinetics, vmax decreased significantly (P < 0.05) and KM increased (although not always significantly) with the increase in t. The conformational changes produced in the starch chains as a consequence of the ageing seemed to affect negatively the diffusivity of the starch to the active site of the enzymes and the release of the reaction products to the medium. A similar effect was observed when the enzymatic reactions were carried out with unaged starches supplemented with different concentrations of gelatine [G]. The inhibition in the amylolytic activities was best mathematically described by using three modified forms of the Michaelis-Menten model, which included a term to consider, respectively, the linear, exponential, and hyperbolic inhibitory effects of t and [G]. PMID:22666116

  14. Thermal analysis of pentaerythritol tetranitrate and development of a powder aging model

    SciTech Connect

    Brown, Geoffrey W; Sandstrom, Mary M; Giambra, Anna M; Archuleta, Jose G; Monroe, Deirde C

    2009-01-01

    We have applied a range of different physical and thermal analysis techniques to characterize the thermal evolution of the specific surface area of pentaerythritol tetranitrate (PETN) powders. Using atomic force microscopy we have determined that the mass transfer mechanism leading to powder coarsening is probably sublimation and redeposition of PETN. Using thermogravimetric analysis we have measured vapor pressures of PETN powders whose aging will be simulated in future work. For one specific powder we have constructed an empirical model of the coarsening that is fit to specific surface area measurements at 60 C to 70 C to provide predictive capability of that powder's aging. Modulated differential scanning calorimetry and mass spectroscopy measurements highlight some of the thermal behavior of the powders and suggest that homologue-based eutectics and impurities are localized in the powder particles.

  15. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

    PubMed

    Forman, Katherine; Vara, Elena; García, Cruz; Kireev, Roman; Cuesta, Sara; Acuña-Castroviejo, Darío; Tresguerres, J A F

    2010-10-01

    This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.

  16. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's disease

    PubMed Central

    Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

    2014-01-01

    Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019

  17. Impact of demographic characteristics in pet ownership: modeling animal count according to owners income and age.

    PubMed

    Martins, Camila Marinelli; Mohamed, Ahmed; Guimarães, Ana Marcia Sá; de Barros, Cristiane da Conceição; Pampuch, Raquel Dos Santos; Svoboda, Walfrido; Garcia, Rita de Cassia Maria; Ferreira, Fernando; Biondo, Alexander Welker

    2013-05-01

    Pet owner characteristics such as age, gender, income/social class, marital status, rural/urban residence and household type have been shown to be associated with the number of owned pets. However, few studies to date have attempted to evaluate these associations in Brazil. Accordingly, the aim of this study was to evaluate the association between age and income of owners and the number of owned dogs and cats in a Brazilian urban center. Pinhais, metropolitan area of Curitiba, Southern Brazil, the seventh largest city in Brazil, was chosen for this study. Questionnaires were administered door-to-door between January and February 2007 and data were analyzed by zero-inflated negative binomial (ZINB) models. A total of 13,555 of 30,380 (44.62%) households were interviewed. The majority (62.43%) of households reported having one or more dogs, with one or two dogs being the most common (29.97% and 19.71%, respectively). Cat ownership per household was much lower (P=0.001) than dog ownership, with 90% of the households reported having no owned cats. ZINB analyses indicated that income is not associated with the number of both dogs and cats among households that have pets. However, households from higher income categories were more likely to have dogs (but not cats) when compared to the lowest income category (P<0.05), contradicting a common belief that the poorer the family, the more likely they have pets. Certain age categories were significantly associated with the number of dogs or cats in households that have pets. In addition, most age categories were significantly associated with having dogs and/or cats (P<0.05). In conclusion, our study has found that age but not household income is associated with the number of dogs or cats in households that have pets; higher income households were more likely to have dogs when compared to low-income households.

  18. Large impact crater histories of Mars: The effect of different model crater age techniques

    NASA Astrophysics Data System (ADS)

    Robbins, Stuart J.; Hynek, Brian M.; Lillis, Robert J.; Bottke, William F.

    2013-07-01

    Impact events that produce large craters primarily occurred early in the Solar System's history because the largest bolides were remnants from planetary formation. Determining when large impacts occurred on a planetary surface such as Mars can yield clues to the flux of material in the early inner Solar System which, in turn, can constrain other planetary processes such as the timing and magnitude of resurfacing and the history of the martian core dynamo. We have used a large, global planetary database in conjunction with geomorphologic mapping to identify craters superposed on the rims of 78 larger craters with diameters D ⩾ 150 km on Mars, ≈78% of which have not been previously dated in this manner. The densities of superposed craters with diameters larger than 10, 16, 25, and 50 km, as well as isochron fits were used to derive model crater ages of these larger craters and basins from which we derived an impact flux. In discussing these ages, we point out several internal inconsistencies of crater-age modeling techniques and chronology systems and, all told, we explain why we think isochron-fitting is the most reliable indicator of an age. Our results point to a mostly obliterated crater record prior to ˜4.0 Ga with the oldest preserved mappable craters on Mars dating to ˜4.3-4.35 Ga. We have used our results to constrain the cessation time of the martian core dynamo which we found to have occurred between the formation of Ladon and Prometheus basins, approximately 4.06-4.09 Ga. We also show that, overall, surfaces on Mars older than ˜4.0-4.1 Ga have experienced >1 km of resurfacing, while those younger than ˜3.8-3.9 Ga have experienced significantly less.

  19. Toward an animal model of extinction-induced despair: focus on aging and physiological indices.

    PubMed

    Huston, Joseph P; Schulz, Daniela; Topic, Bianca

    2009-08-01

    Behaviors that are under the control of positive or negative reinforcers undergo extinction when the anticipated reward/reinforcer is withheld. Despair, an important symptom of environmentally determined depression in humans, can be generated by extinction, or the failure of expected reward to accrue. Although well known to clinicians dealing with depressive patients, an animal model has not been available for extinction-induced depression. We have made a beginning towards validating such a model, based on the extinction of negatively reinforced behavior in the rat, i.e., upon removal of the possibility to escape onto a safety platform in the water maze. As a marker for despair, we employed behavioral immobility, i.e., the cessation of swimming in the attempt to find safety from the water, presumably, a type of learned helplessness. This measure was sensitive to antidepressants and correlated with neurotransmitter contents, neurotrophins and hypothalamus-pituitary adrenal axis markers in selected sites of the brain. Given that some cases of depression in the elderly may be biologically distinct from others and from early-onset depression, and since particularly the aged are prone to experience extinction-induced despair, we compared aged (ca. 24 months old) animals with adults in most of our studies. We found a number of distinct differences in behavioral and biological measures, indicative of differences in propensity to, as well as response to, extinction-induced despair between aged and adults. Our results add to the body of evidence for differences in the neurobiological substrates of depressive disorders between aged and adults, with the implication for the requirement of different treatment strategies in these two populations.

  20. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling.

    PubMed

    González, Oscar C; Krishnan, Giri P; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence; Bazhenov, Maxim

    2015-09-30

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. Significance statement: Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy.

  1. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling

    PubMed Central

    González, Oscar C.; Krishnan, Giri P.; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence

    2015-01-01

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy. PMID:26424890

  2. Age Differences in the Demand–Control Model of Work Stress

    PubMed Central

    Shultz, Kenneth S.; Wang, Mo; Crimmins, Eileen M.; Fisher, Gwenith G.

    2010-01-01

    There have been many tests of Karasek’s demand–control model of work stress. However, no studies have examined how the model may differentially apply to older versus younger workers. Due to age changes in cognitive processing, the psychological demands of jobs may interact differently with controls for younger versus older workers. Therefore, the study uses data from the Eurobarometer to examine how the demand–control model of work stress may function differently for older versus younger workers. The results indicate that different controls may in fact buffer different types of job demands for younger versus older workers. The findings reveal that only the interaction between problem solving and time to complete tasks was significant for younger workers. For older workers, however, the interactions between time deadlines and having sufficient time to complete tasks, autonomy, and the interaction between problem solving and schedule flexibility are significant predictors of self-reported stress. PMID:20948986

  3. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs.

  4. Aging selectively impairs recollection in recognition memory for pictures: Evidence from modeling and ROC curves

    PubMed Central

    Howard, Marc W.; Bessette-Symons, Brandy; Zhang, Yaofei; Hoyer, William J.

    2006-01-01

    Younger and older adults were tested on recognition memory for pictures. The Yonelinas high threshold (YHT) model, a formal implementation of two-process theory, fit the response distribution data of both younger and older adults significantly better than a normal unequal variance signal detection model. Consistent with this finding, non-linear zROC curves were obtained for both groups. Estimates of recollection from the YHT model were significantly higher for younger than older adults. This deficit was not a consequence of a general decline in memory; older adults showed comparable overall accuracy and in fact a non-significant increase in their familiarity scores. Implications of these results for theories of recognition memory and the mnemonic deficit associated with aging are discussed. PMID:16594795

  5. Modeling and prediction of HIV in China: transmission rates structured by infection ages.

    PubMed

    Zhou, Yican; Shao, Yiming; Ruan, Yuhua; Xu, Jianqing; Ma, Zhien; Mei, Changlin; Wu, Jianhong

    2008-04-01

    HIV transmission process involves a long incubation and infection period, and the transmission rate varies greatly with infection stage. Consequently, modeling analysis based on the assumption of a constant transmission rate during the entire infection period yields an inaccurate description of HIV transmission dynamics and long-term projections. Here we develop a general framework of mathematical modeling that takes into account this heterogeneity of transmission rate and permits rigorous estimation of important parameters using a regression analysis of the twenty-year reported HIV infection data in China. Despite the large variation in this statistical data attributable to the knowledge of HIV, surveillance efforts, and uncertain events, and although the reported data counts individuals who might have been infected many years ago, our analysis shows that the model structured on infection age can assist us in extracting from this data set very useful information about transmission trends and about effectiveness of various control measures.

  6. Anti-Skin-Aging Effect of Epigallocatechin Gallate by Regulating Epidermal Growth Factor Receptor Pathway on Aging Mouse Model Induced by D-Galactose.

    PubMed

    Chen, Jiming; Li, Yifan; Zhu, Qiangqiang; Li, Tong; Lu, Hao; Wei, Nan; Huang, Yewei; Shi, Ruoyu; Ma, Xiao; Wang, Xuanjun; Sheng, Jun

    2017-03-23

    Epigallocatechin gallate(EGCG) is a monomer separated from tea catechins, as an well-known antioxidant, which helps fight wrinkles and rejuvenate skin cells. In this study, we investigated the anti-aging effect of EGCG, and to clarify underlying mechanism of skin aging in a D-galactose-induced aging mouse model. Forty-five male mice were divided into 5 groups and treated with different dose of EGCG, Vitamin C (VitC) to mice as a positive control. All groups except vehicle were established aging model induced by D-galactose (200mg/kg/day) that was subcutaneously injected to mice for 8 weeks. Two weeks after injection of D-galactose, EGCG and Vit C groups were simultaneously administered once a day by subcutaneously inject after 5hours for injecting D-galactose. The results show that EGCG can be absorbed by the skin. Overall, the conditions of the skin of EGCG-treatment groups were improved, the whole structure of skin were better than control groups, and the levels of oxidative stress and the expression of relate with EGFR proteins were significantly higher than control group after EGCG treatment. All these findings suggest that EGCG can resist skin senility effectively. And the EGFR with relate of downstream proteins are implicated in the skin aging.

  7. Anti-aging Effect of Transplanted Amniotic Membrane Mesenchymal Stem Cells in a Premature Aging Model of Bmi-1 Deficiency

    PubMed Central

    Xie, Chunfeng; Jin, Jianliang; Lv, Xianhui; Tao, Jianguo; Wang, Rong; Miao, Dengshun

    2015-01-01

    To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1−/− mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of β-galactosidase (β-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old β-gal+ AMSC-transplanted or 6-week-old DiI+ AMSC-transplanted Bmi-1−/− mice were compared with vehicle-transplanted Bmi-1−/− and WT mice. Vehicle-transplanted Bmi-1−/− mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1−/− transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1−/− mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases. PMID:26370922

  8. Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

    NASA Astrophysics Data System (ADS)

    Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

    2014-11-01

    Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

  9. Drosophila as a novel animal model for studying the genetics of age-related memory impairment.

    PubMed

    Saitoe, Minoru; Horiuchi, Junjiro; Tamura, Takuya; Ito, Naomi

    2005-01-01

    Understanding the molecular mechanisms underlying age-related memory impairment (AMI) is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to the development of drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetics to test this hypothesis have not been performed previously, due, in part, to the long lifespan of animal models. Using Drosophila, the first extensive behavioral-genetic characterization of AMI has been carried out. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Significantly, AMI results from the specific decay of only one memory component, amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides that enhance adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a finding consistent with several models of AMI in mammals. Although many advances have been made in the study of pathways involved in aging, much remains to be elucidated on how these pathways affect memory formation to cause AMI. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.

  10. Models for estimating the metabolic syndrome biological age as the new index for evaluation and management of metabolic syndrome

    PubMed Central

    Kang, Young Gon; Suh, Eunkyung; Chun, Hyejin; Kim, Sun-Hyun; Kim, Deog Ki; Bae, Chul-Young

    2017-01-01

    Purpose This study aims to propose a metabolic syndrome (MS) biological age model, through which overall evaluation and management of the health status and aging state in MS can be done easily. Through this model, we hope to provide a novel evaluation and management health index that can be utilized in various health care fields. Patient and methods MS parameters from American Heart Association/National Heart, Lung, and Blood Institute guidelines in 2005 were used as biomarkers for the estimation of MS biological age. MS biological age model development was done by analyzing data of 263,828 participants and clinical application of the developed MS biological age was assessed by analyzing the data of 188,886 subjects. Results The principal component accounted for 36.1% in male and 38.9% in female of the total variance in the battery of five variables. The correlation coefficient between corrected biological age and chronological age in males and females were 0.711 and 0.737, respectively. Significant difference for mean MS biological age and chronological age between the three groups, normal, at risk and MS, was seen (P<0.001). Conclusion For the comprehensive approach in MS management, MS biological age is expected to be additionally utilized as a novel evaluation and management index along with the traditional MS diagnosis. PMID:28203066

  11. Comprehensive Equivalent Circuit Based Modeling and Model Based Management of Aged Lithium ion Batteries

    NASA Astrophysics Data System (ADS)

    Tong, Shijie

    Energy storage is one of society's grand challenges for the 21st century. Lithium ion batteries (LIBs) are widely used in mobile devices, transportation, and stationary energy storages due to lowering cost combined with excellent power/energy density as well as cycle durability. The need for a battery management system (BMS) arises from a demand to improve cycle life, assure safety, and optimize the full pack performance. In this work, we proposed a model based battery on-line state of charge (SoC) and state of health (SoH) estimator for LIBs. The estimator incorporates a comprehensive Equivalent Circuit Model (ECM) as reference, an Extended Kalman Filter (EKF) as state observer, a Recursive Least Square (RLS) algorithm as parameter identifier, and Parameter Varying Approach (PVA) based optimization algorithms for the parameter function regressions. The developed adaptive estimator was applied to a 10kW smart grid energy storage application using retired electric vehicle batteries. The estimator exhibits a high numerical efficiency as well as an excellent accuracy in estimating SoC and SoH. The estimator also provides a novel method to optimize the correlation between battery open circuit voltage (OCV) and SoC, which further improves states estimation accuracy.

  12. The integrate model of emotion, thinking and self regulation: an application to the "paradox of aging".

    PubMed

    Williams, Leanne M; Gatt, Justine M; Hatch, Ainslie; Palmer, Donna M; Nagy, Marie; Rennie, Christopher; Cooper, Nicholas J; Morris, Charlotte; Grieve, Stuart; Dobson-Stone, Carol; Schofield, Peter; Clark, C Richard; Gordon, Evian; Arns, Martijn; Paul, Robert H

    2008-09-01

    This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.

  13. Three layer functional model and energy exchange concept of aging process

    PubMed Central

    Mihajlovic, William

    2006-01-01

    and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions. PMID:23598683

  14. Development of a lifetime prediction model for lithium-ion batteries based on extended accelerated aging test data

    NASA Astrophysics Data System (ADS)

    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.

  15. Testing Models of Psychopathology in Preschool-aged Children Using a Structured Interview-based Assessment

    PubMed Central

    Dougherty, Lea R.; Bufferd, Sara J.; Carlson, Gabrielle A.; Klein, Daniel N.

    2014-01-01

    A number of studies have found that broadband internalizing and externalizing factors provide a parsimonious framework for understanding the structure of psychopathology across childhood, adolescence, and adulthood. However, few of these studies have examined psychopathology in young children, and several recent studies have found support for alternative models, including a bi-factor model with common and specific factors. The present study used parents’ (typically mothers’) reports on a diagnostic interview in a community sample of 3-year old children (n=541; 53.9 % male) to compare the internalizing-externalizing latent factor model with a bi-factor model. The bi-factor model provided a better fit to the data. To test the concurrent validity of this solution, we examined associations between this model and paternal reports and laboratory observations of child temperament. The internalizing factor was associated with low levels of surgency and high levels of fear; the externalizing factor was associated with high levels of surgency and disinhibition and low levels of effortful control; and the common factor was associated with high levels of surgency and negative affect and low levels of effortful control. These results suggest that psychopathology in preschool-aged children may be explained by a single, common factor influencing nearly all disorders and unique internalizing and externalizing factors. These findings indicate that shared variance across internalizing and externalizing domains is substantial and are consistent with recent suggestions that emotion regulation difficulties may be a common vulnerability for a wide array of psychopathology. PMID:24652485

  16. A physics based reduced order aging model for lithium-ion cells with phase change

    NASA Astrophysics Data System (ADS)

    Gambhire, Priya; Hariharan, Krishnan S.; Khandelwal, Ashish; Kolake, Subramanya Mayya; Yeo, Taejung; Doo, Seokgwang

    2014-12-01

    The electrochemical model has the potential to provide a robust and accurate battery management system, but is not the preferred choice as it involves solving non-linear, coupled partial differential equations. In the present work, a model order reduction of the complete electrochemical model for a lithium ion cell with phase change electrodes is carried out. The phase change phenomenon is described using a simple, concentration-dependent diffusivity derived from mixture rules. This reduced order model (ROM) is validated with experimental data from literature. The applicability of the model to capture the atypical behavior of the phase change electrode system is demonstrated. Using the cell response from ROM, charge-discharge asymmetry and path dependence in a lithium iron phosphate (LFP) cell are explored in detail. In addition, side reaction kinetics and solid electrolyte interphase formation are included in the ROM framework to enhance its capability to predict cell aging. The model is used to investigate capacity losses occurring in a phase change electrode cell. Insights from these results are used to suggest cell operating guidelines for maximizing utilization.

  17. Aging and orthopedics: how a lifespan development model can inform practice and research

    PubMed Central

    Gautreau, Sylvia; Gould, Odette N.; Forsythe, Michael E.

    2016-01-01

    Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses that need to be managed over the lifespan. The result is an ongoing shift from curing acute illnesses to the management and care of chronic illness and conditions. Theoretical models that provide a useful and feasible vision for the future of health care and health care research are needed. This review discusses how the lifespan development model used in some disciplines within the behavioural sciences can be seen as an extension of the biopsychosocial model. We posit that the lifespan development model provides useful perspectives for both orthopedic care and research. We present key concepts and recommendations, and we discuss how the lifespan development model can contribute to new and evolving perspectives on orthopedic outcomes and to new directions for research. We also offer practical guidelines on how to implement the model in orthopedic practice. PMID:27240129

  18. A computational model associating learning process, word attributes, and age of acquisition.

    PubMed

    Hidaka, Shohei

    2013-01-01

    We propose a new model-based approach linking word learning to the age of acquisition (AoA) of words; a new computational tool for understanding the relationships among word learning processes, psychological attributes, and word AoAs as measures of vocabulary growth. The computational model developed describes the distinct statistical relationships between three theoretical factors underpinning word learning and AoA distributions. Simply put, this model formulates how different learning processes, characterized by change in learning rate over time and/or by the number of exposures required to acquire a word, likely result in different AoA distributions depending on word type. We tested the model in three respects. The first analysis showed that the proposed model accounts for empirical AoA distributions better than a standard alternative. The second analysis demonstrated that the estimated learning parameters well predicted the psychological attributes, such as frequency and imageability, of words. The third analysis illustrated that the developmental trend predicted by our estimated learning parameters was consistent with relevant findings in the developmental literature on word learning in children. We further discuss the theoretical implications of our model-based approach.

  19. Testing models of psychopathology in preschool-aged children using a structured interview-based assessment.

    PubMed

    Olino, Thomas M; Dougherty, Lea R; Bufferd, Sara J; Carlson, Gabrielle A; Klein, Daniel N

    2014-10-01

    A number of studies have found that broadband internalizing and externalizing factors provide a parsimonious framework for understanding the structure of psychopathology across childhood, adolescence, and adulthood. However, few of these studies have examined psychopathology in young children, and several recent studies have found support for alternative models, including a bi-factor model with common and specific factors. The present study used parents' (typically mothers') reports on a diagnostic interview in a community sample of 3-year old children (n = 541; 53.9 % male) to compare the internalizing-externalizing latent factor model with a bi-factor model. The bi-factor model provided a better fit to the data. To test the concurrent validity of this solution, we examined associations between this model and paternal reports and laboratory observations of child temperament. The internalizing factor was associated with low levels of surgency and high levels of fear; the externalizing factor was associated with high levels of surgency and disinhibition and low levels of effortful control; and the common factor was associated with high levels of surgency and negative affect and low levels of effortful control. These results suggest that psychopathology in preschool-aged children may be explained by a single, common factor influencing nearly all disorders and unique internalizing and externalizing factors. These findings indicate that shared variance across internalizing and externalizing domains is substantial and are consistent with recent suggestions that emotion regulation difficulties may be a common vulnerability for a wide array of psychopathology.

  20. Latency-aged children with attachment disturbances: a conjoint treatment model.

    PubMed

    Shiller, Virginia M

    2011-01-01

    Psychoanalytic theory and practice has increasingly accepted the importance of attachment relationships in psychic development. However, there have been only very limited efforts to develop psychoanalytically informed interventions for older adopted and foster children who show significant disturbances in attachment. This paper reviews theory and research that lays groundwork for a framework for conceptualizing treatment needs for attachment disordered children. Two cases of conjoint work with parents and their latency age sons are presented. The treatment cases highlight the importance of work to increase parents' reflective functioning capacities and the need to challenge children's defensively excluded early internal working models of self and caregivers.

  1. Modeling of Late Blooming Phases and Precipitation Kinetics in Aging Reactor Pressure Vessel (RPV) Steels

    SciTech Connect

    Yongfeng Zhang; Pritam Chakraborty; S. Bulent Biner

    2013-09-01

    The principle work at the atomic scale is to develop a predictive quantitative model for the microstructure evolution of RPV steels under thermal aging and neutron radiation. We have developed an AKMC method for the precipitation kinetics in bcc-Fe, with Cu, Ni, Mn and Si being the alloying elements. In addition, we used MD simulations to provide input parameters (if not available in literature). MMC simulations were also carried out to explore the possible segregation/precipitation morphologies at the lattice defects. First we briefly describe each of the simulation algorithms, then will present our results.

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

    PubMed

    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.

  3. Modelling realistic horizontal branch morphologies and their impact on spectroscopic ages of unresolved stellar systems

    NASA Astrophysics Data System (ADS)

    Percival, Susan M.; Salaris, Maurizio

    2011-04-01

    The presence of an extended blue horizontal branch (HB) in a stellar population is known to affect the age inferred from spectral fitting to stellar population synthesis models. This is due to the hot blue component which increases the strength of the Balmer lines and can make an old population look spuriously young. However, most population synthesis models still rely on theoretical isochrones, which do not include realistic modelling of extended HBs. In this work, we create detailed models for a range of old simple stellar populations (SSPs), with metallicities ranging from [Fe/H]=-1.3 to solar, to create a variety of realistic HB morphologies, from extended red clumps, to extreme blue HBs. We achieve this by utilizing stellar tracks from the BaSTI data base and implementing a different mass-loss prescription for each SSP created. This includes setting an average mass and a Gaussian spread in masses of individual stars coming on to the zero-age HB for each model, and hence resulting in different HB morphologies. We find that, for each metallicity, there is some HB morphology which maximizes Hβ, making an underlying 14-Gyr population look ˜5-6 Gyr old for the low- and intermediate-metallicity cases, and as young as 2 Gyr in the case of the solar metallicity SSP. We explore whether there are any spectral indices capable of breaking the degeneracy between an old SSP with extended blue HB and a truly young or intermediate-age SSP, and find that the Ca II index of Rose and the strength of the Mg II doublet at 2800 Å are promising candidates, in combination with Hβ and other metallicity indicators, such as Mgb and Fe5406. We also run Monte Carlo simulations to investigate the level of statistical fluctuations in the spectra of typical stellar clusters. We find that fluctuations in spectral indices are significant even for average to large globular clusters and that various spectral indices are affected in different ways, which has implications for full

  4. An age-specific kinetic model of lead metabolism in humans.

    PubMed Central

    Leggett, R W

    1993-01-01

    Although considerable progress has been made in recent years in reducing human exposures to lead, the potential for high intake of this contaminant still exists in millions of homes and in many occupational settings. Moreover, there is growing evidence that levels of lead intake considered inconsequential just a few years ago can result in subtle, adverse health effects, particularly in children. Consequently, there have been increased efforts by health protection agencies to develop credible, versatile methods for relating levels of lead in environmental media to levels in blood and tissues of exposed humans of all ages. In a parallel effort motivated largely by the Chernobyl nuclear accident, the International Commission on Radiological Protection (ICRP) is assembling a set of age-specific biokinetic models for calculating radiation doses from environmentally important radionuclides, including radioisotopes of lead. This paper describes a new age-specific biokinetic model for lead originally developed for the ICRP but expanded to include additional features that are useful for consideration of lead as a chemical toxin. The model is developed within a generic, physiologically motivated framework designed to address a class of calciumlike elements. This framework provides a useful setting in which to synthesize experimental, occupational, and environmental data on lead and exploit common physiological properties of lead and the alkaline earth elements. The modular design is intended to allow researchers to modify specific parameter values or model components to address special problems in lead toxicology or to incorporate new information. Transport of lead between compartments is assumed to follow linear, first-order kinetics provided the concentration in red blood cells remains below a nonlinear threshold level, but a nonlinear relation between plasma lead and red blood cell lead is modeled for concentrations above that level. The model is shown to be consistent

  5. [Nutrition, aging, old age].

    PubMed

    Iván, L

    1998-12-06

    In humans there is evidence that the restriction of total caloric intake appears to be more important than the restriction of any particular macronutrient. Today the mechanism of the effect of caloric restriction is unknown. With advancing age and the occurrence of concomitant illness there is an increased risk of developing nutritional deficiencies. Altered nutritional status is associated with the pathogenesis of a number of common diseases of the elderly, thus it would appear that nutritional modulation and manipulation represents one possible approach to successful aging and a healthy longevity. The conceptual framework of the paper suggests the need of a newer light of the aging processes namely by a holistic human-gero-ecological model and a personality oriented geriatry. There are accentuated the role of the nutrients and vitamins, the food intake and drug-nutrients interactions and the meanings of the differences between the normal and pathological aging.

  6. Incorporating harvest rates into the sex-age-kill model for white-tailed deer

    USGS Publications Warehouse

    Norton, Andrew S.; Diefenbach, Duane R.; Rosenberry, Christopher S.; Wallingford, Bret D.

    2013-01-01

    Although monitoring population trends is an essential component of game species management, wildlife managers rarely have complete counts of abundance. Often, they rely on population models to monitor population trends. As imperfect representations of real-world populations, models must be rigorously evaluated to be applied appropriately. Previous research has evaluated population models for white-tailed deer (Odocoileus virginianus); however, the precision and reliability of these models when tested against empirical measures of variability and bias largely is untested. We were able to statistically evaluate the Pennsylvania sex-age-kill (PASAK) population model using realistic error measured using data from 1,131 radiocollared white-tailed deer in Pennsylvania from 2002 to 2008. We used these data and harvest data (number killed, age-sex structure, etc.) to estimate precision of abundance estimates, identify the most efficient harvest data collection with respect to precision of parameter estimates, and evaluate PASAK model robustness to violation of assumptions. Median coefficient of variation (CV) estimates by Wildlife Management Unit, 13.2% in the most recent year, were slightly above benchmarks recommended for managing game species populations. Doubling reporting rates by hunters or doubling the number of deer checked by personnel in the field reduced median CVs to recommended levels. The PASAK model was robust to errors in estimates for adult male harvest rates but was sensitive to errors in subadult male harvest rates, especially in populations with lower harvest rates. In particular, an error in subadult (1.5-yr-old) male harvest rates resulted in the opposite error in subadult male, adult female, and juvenile population estimates. Also, evidence of a greater harvest probability for subadult female deer when compared with adult (≥2.5-yr-old) female deer resulted in a 9.5% underestimate of the population using the PASAK model. Because obtaining

  7. Thermal characterization and model free kinetics of aged epoxies and foams using TGA and DSC methods.

    SciTech Connect

    Cordaro, Joseph Gabriel; Kruizenga, Alan Michael; Nissen, April

    2013-10-01

    Two classes of materials, poly(methylene diphenyl diisocyanate) or PMDI foam, and cross-linked epoxy resins, were characterized using thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC), to help understand the effects of aging and %E2%80%9Cbake-out%E2%80%9D. The materials were evaluated for mass loss and the onset of decomposition. In some experiments, volatile materials released during heating were analyzed via mass spectroscopy. In all, over twenty materials were evaluated to compare the mass loss and onset temperature for decomposition. Model free kinetic (MFK) measurements, acquired using variable heating rate TGA experiments, were used to calculate the apparent activation energy of thermal decomposition. From these compiled data the effects of aging, bake-out, and sample history on the thermal stability of materials were compared. No significant differences between aged and unaged materials were detected. Bake-out did slightly affect the onset temperature of decomposition but only at the highest bake-out temperatures. Finally, some recommendations for future handling are made.

  8. Age-dependent diastolic heart failure in an in vivo Drosophila model

    PubMed Central

    Klassen, Matthew P; Peters, Christian J; Zhou, Shiwei; Williams, Hannah H; Jan, Lily Yeh; Jan, Yuh Nung

    2017-01-01

    While the signals and complexes that coordinate the heartbeat are well established, how the heart maintains its electromechanical rhythm over a lifetime remains an open question with significant implications to human health. Reasoning that this homeostatic challenge confronts all pulsatile organs, we developed a high resolution imaging and analysis toolset for measuring cardiac function in intact, unanesthetized Drosophila melanogaster. We demonstrate that, as in humans, normal aging primarily manifests as defects in relaxation (diastole) while preserving contractile performance. Using this approach, we discovered that a pair of two-pore potassium channel (K2P) subunits, largely dispensable early in life, are necessary for terminating contraction (systole) in aged animals, where their loss culminates in fibrillatory cardiac arrest. As the pumping function of its heart is acutely dispensable for survival, Drosophila represents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging. DOI: http://dx.doi.org/10.7554/eLife.20851.001 PMID:28328397

  9. Nerve growth factor in the adult brain of a teleostean model for aging research: Nothobranchius furzeri.

    PubMed

    D'Angelo, L; Castaldo, L; Cellerino, A; de Girolamo, P; Lucini, C

    2014-07-01

    Nerve growth factor (NGF) acts on central nervous system neurons, regulating naturally occurring cell death, synaptic connectivity, fiber guidance and dendritic morphology. The dynamically regulated production of NGF beginning in development, extends throughout adult life and aging, exerting numerous roles through a surprising variety of neurons and glial cells. This study analyzes the localization of NGF in the brain of the teleost fish Nothobranchius furzeri, an emerging model for aging research due to its short lifespan. Immunochemical and immunohistochemical experiments were performed by employing an antibody mapping at the N-terminus of the mature chain human origin NGF. Western blot analysis revealed an intense and well defined band of 20 kDa, which corresponds to proNGF of N. furzeri. Immunohistochemistry revealed NGF immunoreactivity (IR) diffused throughout all regions of telencephalon, diencephalon, mesencephalon and rhomboencephalon. It was detected in neurons and in glial cells, the latter mostly lining the mesencephalic and rhomboencephalic ventricles. Particularly in neurons, NGF IR was localized in perikarya and, to a less extent, in fibers. The widespread distribution of proNGF suggests that it might modulate numerous physiological functions in the adult brain of N. furzeri. The present survey constitutes a baseline study to enhance the understanding of the mechanisms underlying the role of NGF during aging processes.

  10. Modeling tracers of young stellar population age in star-forming galaxies

    SciTech Connect

    Levesque, Emily M.; Leitherer, Claus

    2013-12-20

    The young stellar population of a star-forming galaxy is the primary engine driving its radiative properties. As a result, the age of a galaxy's youngest generation of stars is critical for a detailed understanding of its star formation history, stellar content, and evolutionary state. Here we present predicted equivalent widths for the Hβ, Hα, and Brγ recombination lines as a function of stellar population age. The equivalent widths are produced by the latest generations of stellar evolutionary tracks and the Starburst99 stellar population synthesis code, and are the first to fully account for the combined effects of both nebular emission and continuum absorption produced by the synthetic stellar population. Our grid of model stellar populations spans six metallicities (0.001 < Z < 0.04), two treatments of star formation history (a 10{sup 6} M {sub ☉} instantaneous burst and a continuous star formation rate of 1 M {sub ☉} yr{sup –1}), and two different treatments of initial rotation rate (v {sub rot} = 0.0v {sub crit} and 0.4v {sub crit}). We also investigate the effects of varying the initial mass function. Given constraints on galaxy metallicity, our predicted equivalent widths can be applied to observations of star-forming galaxies to approximate the age of their young stellar populations.

  11. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging.

    PubMed

    Lescale, Chloé; Schenten, Véronique; Djeghloul, Dounia; Bennabi, Meriem; Gaignier, Fanny; Vandamme, Katleen; Strazielle, Catherine; Kuzniak, Isabelle; Petite, Hervé; Dosquet, Christine; Frippiat, Jean-Pol; Goodhardt, Michele

    2015-02-01

    Within the bone marrow, the endosteal niche plays a crucial role in B-cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground-based model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To this end, we analyzed both bone parameters and the frequency of early hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of HU. We found that limb disuse leads to a decrease in both bone microstructure and the frequency of B-cell progenitors in the bone marrow. Although multipotent hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor (CLP) stage with a major block at the progenitor B (pro-B) to precursor B (pre-B) cell transition (5- to 10-fold decrease). The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B-cell generation in HU mice was associated with reduced expression of B-cell transcription factors, early B-cell factor (EBF) and Pax5, and an alteration in STAT5-mediated IL-7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B-cell differentiation resembling age-related modifications in B lymphopoiesis.

  12. Development of the Japanese reference man model for age-specific phantoms.

    PubMed

    Kawamura, Hisao

    2012-03-01

    Recent interest in improving methods for calculating radiation doses to atomic bomb survivors necessitates reinforcing the data on masses of organs of the Japanese population in 1945, including those that are not calculated by DS02, as well as increasing the number of phantoms for different ages. Reference is made to published data on the masses of organs in normal Japanese subjects of 0-90 y of age with more than 5000 samples during 1970-80, as well as the weight and size of the total body. The first Japanese Reference Man model, primarily based on these data and following the ICRP Reference Man concept, is briefly explained. It provides a set of reference values for males and females of six age groups, i.e. 3 months, 1, 5, 10, 15 and 20-50 y. To consider the organ masses of the Japanese population in 1945, the data during the period 1970-80 are compared with the literature data of normal Japanese reported in 1952. Differences between the two sets of organ data in adults are discussed in relation to changes in the national status of nutrition. Additional organ masses of current interest for the Japanese population in 1945 are preliminarily considered.

  13. Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

    PubMed

    Chollet, François

    2013-03-01

    Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

  14. The use of a random regression model to account for change in racing speed of German trotters with increasing age.

    PubMed

    Bugislaus, A-E; Roehe, R; Willms, F; Kalm, E

    2006-08-01

    In a genetic analysis of German trotters, the performance trait racing time per km was analysed by using a random regression model on six different age classes (2-, 3-, 4-, 5- and 6-year-old and older trotters; the age class of 3-year-old trotters was additionally divided by birth months of horses into two seasons). The best-fitting random regression model for the trait racing time per km on six age classes included as fixed effects sex, race track, condition of race track (fitted as second-order polynomial on age), distance of race and each driver (fitted as first-order polynomial on age) as well as the year-season (fitted independent of age). The random additive genetic and permanent environmental effects were fitted as second-order polynomials on age. Data consisted of 138,620 performance observations from 2,373 trotters and the pedigree data contained 9,952 horses from a four-generation pedigree. Heritabilities for racing time per km increased from 0.01 to 0.18 at age classes from 2- to 4-year-old trotters, then slightly decreased for 5 year and substantially decreased for 6-year-old horses. Genetic correlations of racing time per km among the six age classes were very high (rg = 0.82-0.99). Heritability was h2 = 0.13 when using a repeatability animal model for racing time per km considering the six age classes as fixed effect. Breeding values using repeatability analysis over all and within age classes resulted in slightly different ranking of trotters than those using random regression analysis. When using random regression analysis almost no reranking of trotters over time took place. Generally, the analyses showed that using a random regression model improved the accuracy of selection of trotters over age classes.

  15. Carcinogenically relevant split dose repair increased with age in rat skin model.

    NASA Astrophysics Data System (ADS)

    Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng; Uddin, Ahmed

    2012-07-01

    These experiments utilize cancer induction to evaluate cancer-relevant repair during the interval between dose fractions. Low LET electron radiation(LET ~ 0.34 keV/u) were utilized in experiments that involved exposing rat dorsal skin to 2 equal 8 Gy dose fractions separated at various intervals from 0.25 h to 24 h. Cancer onset was established for 80 weeks after the exposures and only histologically verified cancers were included in the analysis. This experiment involved a total of 540 rats and 880 induced cancers. In the youngest rats (irradiated at 28 days of age) the cancer yield declined with a halftime of approximately 3.5 hrs. In 113 day old rats the cancer yield halftime was shortened to 1.3 hrs. In the oldest rats (182 days of age), the halftime could not be established quantitatively, because it was less than the shortest interval (15 min) utilized in the protocol (best estimate ~5 min). In the oldest rats the cancer yields for all fractionated exposures dropped essentially to the expected level of 2 single fractions, below which theoretically no further reduction is possible. The follow-up times for obtaining cancer yields were the same for all exposure groups in spite of the differing ages at exposure. These results indicate that repair of carcinogenically-relevant damage accelerates with age of the rat. No information is available on the possible mechanistic basis for this finding, although the model might be useful for delineating which of the many postulated split dose repair pathways is the correct one. The finding indicates that older rats should be less susceptible to the carcinogenic action of single doses of low LET radiation in comparison to younger rats, which has been verified in separate studies.

  16. Age-structured mark-recapture analysis: A virtual-population-analysis-based model for analyzing age-structured capture-recapture data

    USGS Publications Warehouse

    Coggins, L.G.; Pine, William E.; Walters, C.J.; Martell, S.J.D.

    2006-01-01

    We present a new model to estimate capture probabilities, survival, abundance, and recruitment using traditional Jolly-Seber capture-recapture methods within a standard fisheries virtual population analysis framework. This approach compares the numbers of marked and unmarked fish at age captured in each year of sampling with predictions based on estimated vulnerabilities and abundance in a likelihood function. Recruitment to the earliest age at which fish can be tagged is estimated by using a virtual population analysis method to back-calculate the expected numbers of unmarked fish at risk of capture. By using information from both marked and unmarked animals in a standard fisheries age structure framework, this approach is well suited to the sparse data situations common in long-term capture-recapture programs with variable sampling effort. ?? Copyright by the American Fisheries Society 2006.

  17. New Ages for Gorgona Island, Colombia: Implications for Previous Petrogenetic and Tectonic Models

    NASA Astrophysics Data System (ADS)

    Serrano Duran, L.; Lopez Martinez, M.; Ferrari, L.

    2007-05-01

    reliable plateau and/or isochron ages. Only one basaltic sample, located in the western coast, yielded an age comparable with those previously reported in the literature. For two basalts intercalated with komatiites and a gabbro exposed in the north-eastern coast of the island we obtained younger ages, similar to those reported for some mafic and ultramafic rocks along the Pacific coast of Colombia. The two sets of ages for the ultramafic suite of Gorgona also correspond to different petrologic types. The depleted rocks in the eastern coast are younger than the enriched basalts and picrites located in the southern and western part of the island with ages around 90 Ma, suggesting a more complex tectonic evolution with the accretion of at least two different blocks. This eventually questions the "single plume" model for the formation of the Gorgona Island plateau.

  18. Lack of spontaneous age-related brain pathology in Octodon degus: a reappraisal of the model

    PubMed Central

    Bourdenx, Mathieu; Dovero, Sandra; Thiolat, Marie-Laure; Bezard, Erwan; Dehay, Benjamin

    2017-01-01

    Neurodegenerative diseases are characterized by the degeneration of specific brain areas associated with accumulation of disease-related protein in extra- or intra-cellular deposits. Their preclinical investigations are mostly based on genetically-engineered animals. Despite their interest, these models are often based on high level of disease-related protein expression, thus questioning their relevance to human pathology and calling for the alternate use of ecological models. In the past few years, Octodon degus has emerged as a promising animal model displaying age-dependent Alzheimer’s disease-related pathology. As neurodegenerative-related proteins often co-deposit in the brain of patients, we assessed the occurrence of α-synuclein-related pathology in this model using state-of-the-art immunohistochemistry and biochemistry. Despite our efforts and in contrast with previously published results, our study argues against the use of Octodon degus as a suitable natural model of neurodegenerative disorder as we failed to identify either Parkinson’s disease- or Alzheimer’s disease-related brain pathologies. PMID:28374864

  19. The structure of horizontal-branch models. I - The zero-age horizontal branch

    NASA Technical Reports Server (NTRS)

    Dorman, Ben

    1992-01-01

    A detailed study of the structure of zero-age horizontal-branch (ZAHB) models is studied in order to show how the hydrostatic structure of these models changes with the input parameters and determines the H-R diagram location of a given model. The properties of composite polytropes on the homology-invariant (U,V)-plane are demonstrated. A variety of test models and sequences were constructed to elucidate the underlying factors that give rise to the wide variation in HB model properties with composition. The roles of the CNO elements as nuclear catalysts and of the envelope sources, as well as the envelope helium abundance are reexamined. It is found that, for stars of a fixed range of mass arriving on the HB, the stellar distribution is determined mainly by CNO for low metallicities (Fe/H of less than about -1), but mainly by opacity sources for high metallicities. The value of Fe/H where CNO ceases to dominate depends significantly on the adopted opacity and will decrease if and when opacity estimates are revised upward.

  20. Modeling abrupt cultural regime shifts during the Palaeolithic and Stone Age.

    PubMed

    Aoki, Kenichi

    2014-12-07

    The coupled dynamics of the size and the mean cultural/technological level of a population, with positive feedback between these two variables, is modeled in the Malthusian-Boserupian framework. Bifurcation diagrams, with innovativeness or the cultureless carrying capacity as the parameter, show that abrupt transitions in the mean cultural level are possible. For example, a gradual evolutionary change toward greater innate innovativeness would produce an associated gradual increase in mean cultural level, until a threshold is crossed that triggers an abrupt cultural regime shift. Hence, the model may help explain the apparently sudden and dramatic efflorescences of Palaeolithic/Stone Age culture during the Late Pleistocene, without having to invoke major contemporaneous genetic changes in cognition. The results of statistical studies on the association between population size and toolkit diversity among ethnographic societies are also discussed.

  1. A Rat Model System to Study Complex Disease Risks, Fitness, Aging, and Longevity

    PubMed Central

    Koch, Lauren Gerard; Britton, Steven L.; Wisløff, Ulrik

    2012-01-01

    The association between low exercise capacity and all-cause morbidity and mortality is statistically strong yet mechanistically unresolved. By connecting clinical observation with a theoretical base, we developed a working hypothesis that variation in capacity for oxygen metabolism is the central mechanistic determinant between disease and health (aerobic hypothesis). As an unbiased test, we show that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity. This contrasting animal model system may prove to be translationally superior, relative to more widely-used simplistic models for understanding geriatric biology and medicine. PMID:22867966

  2. Little Ice Age glaciers in Britain: Glacier–climate modelling in the Cairngorm Mountains

    SciTech Connect

    Stephan Harrison; Ann V. Rowan; Neil F. Glasser; Jasper Knight; Mitchell A. Plummer; Stephanie C. Mills

    2014-02-01

    It is widely believed that the last glaciers in the British Isles disappeared at the end of the Younger Dryas stadial (12.9–11.7 cal. kyr BP). Here, we use a glacier–climate model driven by data from local weather stations to show for the first time that glaciers developed during the Little Ice Age (LIA) in the Cairngorm Mountains. Our model is forced from contemporary conditions by a realistic difference in mean annual air temperature of -1.5 degrees C and an increase in annual precipitation of 10%, and confirmed by sensitivity analyses. These results are supported by the presence of small boulder moraines well within Younger Dryas ice limits, and by a dating programme on a moraine in one cirque. As a result, we argue that the last glaciers in the Cairngorm Mountains (and perhaps elsewhere in upland Britain) existed in the LIA within the last few hundred years, rather than during the Younger Dryas.

  3. Parameterizing age patterns of demographic rates with the multiexponential model schedule.

    PubMed

    Rogers, A; Little, J S

    1994-02-01

    "For nearly 200 years actuaries, statisticians, and demographers have sought to summarize the age pattern of mortality rates by means of a limited number of parameters. Such 'model schedules' have also been useful in representing schedules of rates other than mortality....This paper illustrates a particular general functional form for such model schedules: the multiexponential function. It discusses the changing behavior of this function as its parameters take on different values and examines the quality of the fits of this function to observed data on mortality, fertility, and migration." This is a revised version of a paper originally presented at the 1993 Annual Meeting of the Population Association of America. (SUMMARY IN FRE)

  4. Interplay of Aging and Hypertension in Cardiac Remodeling: A Mathematical Geometric Model

    PubMed Central

    Tsai, Meng-Hang; Tsai, Wei-Chuan

    2016-01-01

    Hypertensive disorder can cause cardiac deformities. Elastic characteristic parameters, like Young’s modulus of elasticity (E) derived from a traditional cylindrical model, increase significantly with aging. However, the geometric and component changes of aging hearts because of chronic hypertension remain unknown. To better describe the effects, we propose an elliptical elastic and mathematical model to evaluate myocardial stiffness. Ninety-six hypertensive patients (HTNPos) (men: 59.3%; age ≥ 65 years: 20.8%) were enrolled and compared with normotensive controls (HTNNeg) (n = 47, 48.9%). HTNPos patients had a thicker interventricular septum in diastole (IVSd) (HTNPos: 0.96 ± 0.21 cm vs. HTNNeg: 0.77 ± 0.15; p = 0.005) and higher intracardiac pressure (e/e′: 9.06 ± 4.85 cm vs. 7.76 ± 3.41; p = 0.01), especially the elderly (> 65 years) (IVSd: 1.03 ± 0.19 cm, e/e′: 11.39 ± 1.99; p = 0.006 and 0.01, respectively). Nevertheless, the internal dimension decreased more significantly in the HTNPos rather than in the HTNNeg elderly (5.23 ± 0.46 vs. 4.74 ± 0.69 cm; p = 0.02). We found different directions of cardiac remodeling with normotensive and hypertensive loads. Different from the longitudinal and circumferential strain, E and Poisson’s ratio (υ) are values that directly present the rigidity of myocardium. E was significantly higher in the elderly (8011.92 ± 2431.85 vs. 6052.43 ± 3121.50; p = 0.02), whereas υ was significantly higher in all HTNPos patients (0.73 ± 0.12 vs. 0.61 ± 0.07; p < 0.001). Because E and υ reflected the material changes of myocardium in the HTNPos elderly, the proposed elliptical mathematical heart model better describes the geometric deformity induced by aging and hypertension. PMID:27977729

  5. Numerical Modeling of the Last Glacial Maximum Yellowstone Ice Cap Captures Asymmetry in Moraine Ages

    NASA Astrophysics Data System (ADS)

    Anderson, L. S.; Wickert, A. D.; Colgan, W. T.; Anderson, R. S.

    2014-12-01

    The Last Glacial Maximum (LGM) Yellowstone Ice Cap was the largest continuous ice body in the US Rocky Mountains. Terminal moraine ages derived from cosmogenic radionuclide dating (e.g., Licciardi and Pierce, 2008) constrain the timing of maximum Ice Cap extent. Importantly, the moraine ages vary by several thousand years around the Ice Cap; ages on the eastern outlet glaciers are significantly younger than their western counterparts. In order to interpret these observations within the context of LGM climate in North America, we perform two numerical glacier modeling experiments: 1) We model the initiation and growth of the Ice Cap to steady state; and 2) We estimate the range of LGM climate states which led to the formation of the Ice Cap. We use an efficient semi-implicit 2-D glacier model coupled to a fully implicit solution for flexural isostasy, allowing for transient links between climatic forcing, ice thickness, and earth surface deflection. Independent of parameter selection, the Ice Cap initiates in the Absaroka and Beartooth mountains and then advances across the Yellowstone plateau to the west. The Ice Cap advances to its maximum extent first to the older eastern moraines and last to the younger western and northwestern moraines. This suggests that the moraine ages may reflect the timescale required for the Ice Cap to advance across the high elevation Yellowstone plateau rather than the timing of local LGM climate. With no change in annual precipitation from the present, a mean summer temperature drop of 8-9° C is required to form the Ice Cap. Further parameter searches provide the full range of LGM paleoclimate states that led to the Yellowstone Ice Cap. Using our preferred parameter set, we find that the timescale for the growth of the complete Ice Cap is roughly 10,000 years. Isostatic subsidence helps explain the long timescale of Ice Cap growth. The Yellowstone Ice Cap caused a maximum surface deflection of 300 m (using a constant effective elastic

  6. Retinal Ultrastructure of Murine Models of Dry Age-related Macular Degeneration (AMD)

    PubMed Central

    Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao

    2010-01-01

    Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch’s membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr−/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh−/−, Ccl2−/−, Ccr2−/−, Cx3cr1−/−, and Ccl2−/−/cx3cr1−/−, oxidative stress associated genes such as Sod1−/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp−/−/Heph−/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically

  7. A Comparison of the Lower Stratospheric Age-Spectra Derived from a General Circulation Model and Two Data Assimilation Systems

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark R.; Douglass, Anne R.; Zhu, Zhengxin; Pawson, Steven

    2002-01-01

    We use kinematic and diabatic back trajectory calculations, driven by winds from a general circulation model (GCM) and two different data assimilation systems (DAS), to compute the age spectrum at three latitudes in the lower stratosphere. The age-spectra are compared to chemical transport model (CTM) calculations, and the mean ages from all of these studies are compared to observations. The age spectra computed using the GCM winds show a reasonably isolated tropics in good agreement with observations; however, the age spectra determined from the DAS differ from the GCM spectra. For the DAS diabatic trajectory calculations there is too much exchange between the tropics and mid-latitudes. The age spectrum is thus too broad and the tropical mean age is too old as a result of mixing older mid latitude air with tropical air. Likewise the mid latitude mean age is too young due to the in mixing of tropical air. The DAS kinematic trajectory calculations show excessive vertical dispersion of parcels in addition to excessive exchange between the tropics and mid latitudes. Because air is moved rapidly to the troposphere from the vertical dispersion, the age spectrum is shifted toward the young side. The excessive vertical and meridional dispersion compensate in the kinematic case giving a reasonable tropical mean age. The CTM calculation of the age spectrum using the DAS winds shows the same vertical and meridional dispersive characteristics of the kinematic trajectory calculation. These results suggest that the current DAS products will not give realistic trace gas distributions for long integrations; they also help explain why the extra tropical mean ages determined in a number of previous DAS driven CTM s are too young compared with observations. Finally, we note trajectory-generated age spectra . show significant age anomalies correlated with the seasonal cycles. These anomalies can be linked to year-to-year variations in the tropical heating rate. The anomalies are

  8. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model.

    PubMed

    Nikolaidis, Michalis G; Kyparos, Antonios; Spanou, Chrysa; Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Grivas, Gerasimos V; Zafeiridis, Andreas; Dipla, Konstantina; Vrabas, Ioannis S

    2013-08-01

    Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6±0.5 years) and ten elderly men (64.6±1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F2-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans.

  9. Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

    PubMed Central

    2017-01-01

    Cell proliferation is the common characteristic of all biological systems. The immune system insures the maintenance of body integrity on the basis of a continuous production of diversified T lymphocytes in the thymus. This involves processes of proliferation, differentiation, selection, death and migration of lymphocytes to peripheral tissues, where proliferation also occurs upon antigen recognition. Quantification of cell proliferation dynamics requires specific experimental methods and mathematical modelling. Here, we assess the impact of genetics and aging on the immune system by investigating the dynamics of proliferation of T lymphocytes across their differentiation through thymus and spleen in mice. Our investigation is based on single-cell multicolour flow cytometry analysis revealing the active incorporation of a thymidine analogue during S phase after pulse-chase-pulse experiments in vivo, versus cell DNA content. A generic mathematical model of state transition simulates through Ordinary Differential Equations (ODEs) the evolution of single cell behaviour during various durations of labelling. It allows us to fit our data, to deduce proliferation rates and estimate cell cycle durations in sub-populations. Our model is simple and flexible and is validated with other durations of pulse/chase experiments. Our results reveal that T cell proliferation is highly heterogeneous but with a specific “signature” that depends upon genetic origins, is specific to cell differentiation stages in thymus and spleen and is altered with age. In conclusion, our model allows us to infer proliferation rates and cell cycle phase durations from complex experimental 5-ethynyl-2'-deoxyuridine (EdU) data, revealing T cell proliferation heterogeneity and specific signatures. PMID:28288157

  10. Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background.

    PubMed

    Vibert, Julien; Thomas-Vaslin, Véronique

    2017-03-01

    Cell proliferation is the common characteristic of all biological systems. The immune system insures the maintenance of body integrity on the basis of a continuous production of diversified T lymphocytes in the thymus. This involves processes of proliferation, differentiation, selection, death and migration of lymphocytes to peripheral tissues, where proliferation also occurs upon antigen recognition. Quantification of cell proliferation dynamics requires specific experimental methods and mathematical modelling. Here, we assess the impact of genetics and aging on the immune system by investigating the dynamics of proliferation of T lymphocytes across their differentiation through thymus and spleen in mice. Our investigation is based on single-cell multicolour flow cytometry analysis revealing the active incorporation of a thymidine analogue during S phase after pulse-chase-pulse experiments in vivo, versus cell DNA content. A generic mathematical model of state transition simulates through Ordinary Differential Equations (ODEs) the evolution of single cell behaviour during various durations of labelling. It allows us to fit our data, to deduce proliferation rates and estimate cell cycle durations in sub-populations. Our model is simple and flexible and is validated with other durations of pulse/chase experiments. Our results reveal that T cell proliferation is highly heterogeneous but with a specific "signature" that depends upon genetic origins, is specific to cell differentiation stages in thymus and spleen and is altered with age. In conclusion, our model allows us to infer proliferation rates and cell cycle phase durations from complex experimental 5-ethynyl-2'-deoxyuridine (EdU) data, revealing T cell proliferation heterogeneity and specific signatures.

  11. BMP9/ALK1 inhibits neovascularization in mouse models of age-related macular degeneration

    PubMed Central

    Ntumba, Kalonji; Akla, Naoufal; Oh, S. Paul; Eichmann, Anne; Larrivée, Bruno

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations of industrialized countries. The drawbacks of inhibitors of vascular endothelial growth factor (VEGFs) currently used for the treatment of AMD, which include resistance and potential serious side-effects, require the identification of new therapeutic targets to modulate angiogenesis. BMP9 signaling through the endothelial Alk1 serine-threonine kinase receptor modulates the response of endothelial cells to VEGF and promotes vessel quiescence and maturation during development. Here, we show that BMP9/Alk1 signaling inhibits neovessel formation in mouse models of pathological ocular angiogenesis relevant to AMD. Activating Alk1 signaling in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) inhibited neovascularization and reduced the volume of vascular lesions. Alk1 signaling was also found to interfere with VEGF signaling in endothelial cells whereas BMP9 potentiated the inhibitory effects of VEGFR2 signaling blockade, both in OIR and laser-induced CNV. Together, our data show that targeting BMP9/Alk1 efficiently prevents the growth of neovessels in AMD models and introduce a new approach to improve conventional anti-VEGF therapies. PMID:27517154

  12. Circadian typology, age, and the alternative five-factor personality model in an adult women sample.

    PubMed

    Muro, Anna; Gomà-i-Freixanet, Montserrat; Adan, Ana; Cladellas, Ramon

    2011-10-01

    Research on personality and circadian typology indicates evening-type women are more impulsive and novelty seeking, neither types are more anxious, and morning types tend to be more active, conscientious, and persistent. The purpose of this study is to examine the differences between circadian typologies in the light of the Zuckerman's Alternative Five-Factor Model (AFFM) of personality, which has a strong biological basis, in an adult sample of 412 women 18 to 55 yrs of age. The authors found morning-type women had significant higher scores than evening-type and neither-type women on Activity, and its subscales General Activity and Work Activity. In contrast, evening-type women scored significantly higher than morning-type women on Aggression-Hostility, Impulsive Sensation Seeking, and its subscale Sensation Seeking. In all groups, results were independent of age. These findings are in accordance with those previously obtained in female student samples and add new data on the AFFM. The need of using personality models that are biologically based in the study of circadian rhythms is discussed.

  13. Using synthetic models to simulate aging of Cu contamination in soils.

    PubMed

    Proffit, S; Marin, B; Cances, B; Ponthieu, M; Sayen, S; Guillon, E

    2015-05-01

    The Bureau Commun de Référence (BCR) sequential extraction scheme and micro-synchrotron-based X-ray fluorescence (μ-SXRF) analysis were used to determine the Cu fractionation in a calcareous vineyard soil and a synthetic soil (mixture of seven constituents: calcite, birnessite, ferrihydrite, goethite, lignocellulosic residue, kaolinite, and quartz) at different Cu contamination rates (190, 1270, and 6350 mg kg(-1) of Cu) and aging times (1, 30, 92, and 181 days). The Cu distribution in the spiked vineyard and synthetic soils was different from the original vineyard one and was influenced by the loading level. The newly added Cu was preferentially present in the acid soluble fraction. Aging of the contaminated vineyard and synthetic soils during 6 months led to the redistribution of Cu from the weakly bound acid soluble fraction to the strongly bound reducible one. The evolution with time could satisfactorily be simulated by the Elovich diffusion model for the synthetic soils. It was less significant as less marked in the contaminated vineyard soil than in the synthetic one, even though the trends observed in both were similar. This study supported the hypothesis that "simple" synthetic models could be used to approach the Cu fractionation and its evolution with time in vineyard soils.

  14. A Model-based Prognostics Methodology for Electrolytic Capacitors Based on Electrical Overstress Accelerated Aging

    NASA Technical Reports Server (NTRS)

    Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai

    2011-01-01

    A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

  15. Fragmentation dynamics within shear bands-a model for aging tectonic faults?

    NASA Astrophysics Data System (ADS)

    Åström, J. A.; Herrmann, H. J.; Timonen, J.

    2001-03-01

    A numerical model for packing of fragmenting blocks in a shear band is introduced, and its dynamics is compared with that of a tectonic fault. The shear band undergoes a slow aging process in which the blocks are being grinded by the shear motion and the compression. The dynamics of the model have the same statistical characteristics as the seismic activity in faults. The characteristic magnitude distribution of earthquakes appears to result from frictional slips at small and medium magnitudes, and from fragmentation of blocks at the largest magnitudes. Aftershocks to large-magnitude earthquakes are local recombinations of the fragments before they reach a new quasi-static equilibrium. The aftershocks satisfy Omori's law. Local precursor activity at a few times the normal background level appears at a short time before a major earthquake. Seismic gaps appear as a natural consequence of the aging process of a fault. Explanation of the heat flux and principal stress direction anomalies at the faults both involve the value of fracture stress of the blocks in the gouge. The final form of a tectonic fault is predicted to involve a gouge dominated by fine-grained and rather rounded blocks so that it cannot withstand large shear stresses.

  16. Immune response in virus model structured by cell infection-age.

    PubMed

    Browne, Cameron

    2016-10-01

    This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production. The kinetics of epitope presentation and immune recognition can impact the efficacy of the immune response. We extend previous virus models to include cell infection-age structure in the infected cell compartment and immune response killing/activation rates of a PDE-ODE system. We characterize solutions to our system utilizing semigroup theory, determine equilibria and reproduction numbers, and prove stability and persistence results. Numerical simulations show that ' early immune recognition' precipitates both enhanced viral control and sustained oscillations via a Hopf bifurcation. In addition to inducing oscillatory dynamics, considering immune process rates to be functions of cell infection-age can also lead to coexistence of multiple distinct immune effector populations.

  17. Age model for a continuous, ca 250-ka Quaternary lacustrine record from Bear Lake, Utah-Idaho

    USGS Publications Warehouse

    Colman, Steven M.; Kaufman, D.S.; Bright, Jordon; Heil, C.; King, J.W.; Dean, W.E.; Rosenbaum, J.G.; Forester, R.M.; Bischoff, J.L.; Perkins, Marie; McGeehin, J.P.

    2006-01-01

    The Quaternary sediments sampled by continuous 120-m-long drill cores from Bear Lake (Utah-Idaho) comprise one of the longest lacustrine sequences recovered from an extant lake. The cores serve as a good case study for the construction of an age model for sequences that extend beyond the range of radiocarbon dating. From a variety of potential age indicators, we selected a combination of radiocarbon ages, one magnetic excursion (correlated to a standard sequence), and a single Uranium-series age to develop an initial data set. The reliability of the excursion and U-series data require consideration of their position with respect to sediments of inferred interglacial character, but not direct correlation with other paleoclimate records. Data omitted from the age model include amino acid age estimates, which have a large amount of scatter, and tephrochronology correlations, which have relatively large uncertainties. Because the initial data set was restricted to the upper half of the BL00-1 core, we inferred additional ages by direct correlation to the independently dated paleoclimate record from Devils Hole. We developed an age model for the entire core using statistical methods that consider both the uncertainties of the original data and that of the curve-fitting process, with a combination of our initial data set and the climate correlations as control points. This age model represents our best estimate of the chronology of deposition in Bear Lake. Because the age model contains assumptions about the correlation of Bear Lake to other climate records, the model cannot be used to address some paleoclimate questions, such as phase relationships with other areas.

  18. Faculties of Education in Traditional Universities and Universities of the Third Age: A Partnership Model in Gerontagogy

    ERIC Educational Resources Information Center

    Lemieux, Andre; Boutin, Gerald; Riendeau, Jean

    2007-01-01

    This article discusses "Universities of the Third Age", whose function is quite distinct from established universities' traditional role in teaching, research, and community services. Consequently, there is an urgent need to develop a model of partnership between traditional universities and Universities of the Third Age, ensuring better…

  19. Random regression models on Legendre polynomials to estimate genetic parameters for weights from birth to adult age in Canchim cattle.

    PubMed

    Baldi, F; Albuquerque, L G; Alencar, M M

    2010-08-01

    The objective of this work was to estimate covariance functions for direct and maternal genetic effects, animal and maternal permanent environmental effects, and subsequently, to derive relevant genetic parameters for growth traits in Canchim cattle. Data comprised 49,011 weight records on 2435 females from birth to adult age. The model of analysis included fixed effects of contemporary groups (year and month of birth and at weighing) and age of dam as quadratic covariable. Mean trends were taken into account by a cubic regression on orthogonal polynomials of animal age. Residual variances were allowed to vary and were modelled by a step function with 1, 4 or 11 classes based on animal's age. The model fitting four classes of residual variances was the best. A total of 12 random regression models from second to seventh order were used to model direct and maternal genetic effects, animal and maternal permanent environmental effects. The model with direct and maternal genetic effects, animal and maternal permanent environmental effects fitted by quadric, cubic, quintic and linear Legendre polynomials, respectively, was the most adequate to describe the covariance structure of the data. Estimates of direct and maternal heritability obtained by multi-trait (seven traits) and random regression models were very similar. Selection for higher weight at any age, especially after weaning, will produce an increase in mature cow weight. The possibility to modify the growth curve in Canchim cattle to obtain animals with rapid growth at early ages and moderate to low mature cow weight is limited.

  20. An age-dependent branching process model for the analysis of CFSE-labeling experiments

    PubMed Central

    2010-01-01

    Background Over the past decade, flow cytometric CFSE-labeling experiments have gained considerable popularity among experimentalists, especially immunologists and hematologists, for studying the processes of cell proliferation and cell death. Several mathematical models have been presented in the literature to describe cell kinetics during these experiments. Results We propose a multi-type age-dependent branching process to model the temporal development of populations of cells subject to division and death during CFSE-labeling experiments. We discuss practical implementation of the proposed model; we investigate a competing risk version of the process; and we identify the classes of cellular dependencies that may influence the expectation of the process and those that do not. An application is presented where we study the proliferation of human CD8+ T lymphocytes using our model and a competing risk branching process. Conclusions The proposed model offers a widely applicable approach to the analysis of CFSE-labeling experiments. The model fitted very well our experimental data. It provided reasonable estimates of cell kinetics parameters as well as meaningful insights into the processes of cell division and cell death. In contrast, the competing risk branching process could not describe the kinetics of CD8+ T cells. This suggested that the decision of cell division or cell death may be made early in the cell cycle if not in preceding generations. Also, we show that analyses based on the proposed model are robust with respect to cross-sectional dependencies and to dependencies between fates of linearly filiated cells. Reviewers This article was reviewed by Marek Kimmel, Wai-Yuan Tan and Peter Olofsson. PMID:20569476

  1. The Development and Evaluation of a Professional Development Model to Build Meaningful and Effective IEPs for Transition-Aged Students

    ERIC Educational Resources Information Center

    Doren, Bonnie; Flannery, K. Brigid; Lombardi, Allison

    2012-01-01

    The purpose of the study was to examine the potential efficacy of a professional development training model targeting IEP case managers of transition-age students. A training model was developed and a pilot study conducted to understand the promise of the model to improve the development of critical components within the IEP document that support…

  2. Motion of Hawaii and Louisville hotspots: Comparision of modeling results with new age and paleolatitude data

    NASA Astrophysics Data System (ADS)

    Steinberger, B. M.; O'Connor, J. M.; Koppers, A. A.

    2011-12-01

    The bend in the Hawaiian-Emperor Chain is often seen as a consequence of Pacific plate motion change. Alternatively, it may record a change in motion of the Hawaii hotspot, or a combination of both. In order to devise a common reference frame for plate motions and flow in the mantle, which is needed to understand plate-mantle interaction, it is important to resolve that issue. Here we contribute towards that goal by comparing predictions of a geodynamic model of hotspot motion with new age and paleolatitude data from the Hawaiian-Emperor and Louisville chains. These are the two most prominent hotspot tracks on the Pacific plate and hence most suitable to constrain its motion. Comparing the age progression along both tracks can tell about the relative motion or fixity of the two hotspots, whereas paleo-latitude data ideally can resolve hotspot motion relative to the pole. However, their interpretation also needs to consider the possibility of true polar wander -- re-orientation of the entire Earth including the mantle relative to the pole. To model hotspot motion, we first compute large-scale mantle flow. Mantle density anomalies are inferred from seismic tomography models, assuming both density and seismic velocity anomalies are due to temperature anomalies, except in parts of the uppermost mantle (tectosphere) and possibly parts of the lowermost mantle (Large Low Shear Velocity Provinces). Radial mantle viscosity structure is chosen such that it is consistent with mineral physics, and the "Haskell average" inferred from postglacial rebound observations, and the model prediction of the geoid and global heat flux agrees well with observations. Time dependence is achieved by considering changes in plate motions and geometry as mantle flow boundary conditions, and advecting density anomalies back with the flow. Secondly we compute the motion of plume conduits in large-scale flow, assuming conduits are vertical at an initial time, and subsequently move with the flow

  3. The Changing Nature of Adult Education in the Age of Transnational Migration: Toward a Model of Recognitive Adult Education

    ERIC Educational Resources Information Center

    Guo, Shibao

    2015-01-01

    This chapter examines the changing nature of adult education in the age of transnational migration and proposes recognitive adult education as an inclusive model that acknowledges and affirms cultural difference and diversity as positive and desirable assets.

  4. Predicting Age-appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically-based Pharmacokinetic Modeling (T)

    EPA Science Inventory

    The capability of physiologically-based pharmacokinetic (PBPK) models to incorporate ageappropriate physiological and chemical-specific parameters was utilized in this study to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages o...

  5. PREDICTING AGE-DEPENDENT PHARMACOKINETICS OF SIX VOLATILE ORGANIC COMPOUNDS UTILIZING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING OF RAT

    EPA Science Inventory

    In this study, age-appropriate physiological and chemical-specific parameters were incorporated into a physiologically based pharmacokinetic (PBPK) model to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different lifestages of the rat and ...

  6. Predicting water age distribution in the Pearl River Estuary using a three-dimensional model

    NASA Astrophysics Data System (ADS)

    Ren, Yuheng; Lin, Binliang; Sun, Jian; Pan, Shunqi

    2014-11-01

    The age of water (AW) concept is applied to investigate the water exchange process in a large and density stratified estuary, namely the Pearl River Estuary. A three-dimensional AW model has been built based on an existing hydrodynamic and solute transport model. The model is used to determine the AW distributions inside the Pearl River Estuary under various hydrodynamic conditions. The predicted mean AW values during the dry and wet seasons are approximately 25 and 10 days, respectively. In general, lower AW values are observed in the upper layers near the water surface, while higher values are observed in the lower layers near the bed. The difference becomes more pronounced during