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At least 343 records · Page 19

Disentangling Alzheimer’s disease neurodegeneration from typical brain ageing using machine learning

Abstract Neuroimaging biomarkers that distinguish between changes due to typical brain ageing and Alzheimer’s disease are valuable for determining how much each contributes to cognitive decline. Supervised machine learning models can derive multivariate patterns of brain change related to the two processes, including the Spatial Patterns of Atrophy for Recognition of Alzheimer’s Disease (SPARE-AD) and of Brain Aging (SPARE-BA) scores investigated herein. However, the substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology, and associated results, towards disentangling the two. T1-weighted MRI scans of 4054 participants (48–95 years) with Alzheimer’s disease, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases (iSTAGING) consortium were analysed. Multiple sets of SPARE scores were investigated, in order to probe imaging signatures of certain clinically or molecularly defined sub-cohorts. First, a subset of clinical Alzheimer’s disease patients (n = 718) and age- and sex-matched CN adults (n = 718) were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus Alzheimer’s disease) models. Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2 models: amyloid-positive Alzheimer’s disease continuum group (n = 718; consisting of amyloid-positive Alzheimer’s disease, amyloid-positive MCI, amyloid- and tau-positive CN individuals) and amyloid-negative CN group (n = 718). Finally, the combined group of the Alzheimer’s disease continuum and amyloid-negative CN individuals was used to train SPARE-BA3 model, with the intention to estimate brain age regardless of Alzheimer’s disease-related brain changes. The disentangled SPARE models, SPARE-AD2 and SPARE-BA3, derived brain patterns that were more specific to the two types of brain changes. The correlation between the SPARE-BA Gap (SPARE-BA minus chronological age) and SPARE-AD was significantly reduced after the decoupling (r = 0.56–0.06). The correlation of disentangled SPARE-AD was non-inferior to amyloid- and tau-related measurements and to the number of APOE ε4 alleles but was lower to Alzheimer’s disease-related psychometric test scores, suggesting the contribution of advanced brain ageing to the latter. The disentangled SPARE-BA was consistently less correlated with Alzheimer’s disease-related clinical, molecular and genetic variables. By employing conservative molecular diagnoses and introducing Alzheimer’s disease continuum cases to the SPARE-BA model training, we achieved more dissociable neuroanatomical biomarkers of typical brain ageing and Alzheimer’s disease.

Hwang, Gyujoon↗

Systemic clearance of p16 INK4a -positive senescent cells mitigates age-associated intervertebral disc degeneration

RATIONALE:Age-related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age-related IDD. OBJECTIVE:The study aimed to elucidate whether a causal relationship exists between cellular senescence and age-related IDD. METHODS AND RESULTS:To examine the impact of senescent cells on age-associated IDD, we used p16-3MR transgenic mice, which enables the selective removal of p16 INK4a -positive senescent cells by the drug ganciclovir. Disc cellularity, aggrecan content and fragmentation alongside expression of inflammatory cytokine (IL-6) and matrix proteases (ADAMTS4 and MMP13) in discs of p16-3MR mice treated with GCV and untreated controls were assessed. In aged mice, reducing the per cent of senescent cells decreased disc aggrecan proteolytic degradation and increased overall proteoglycan matrix content along with improved histological disc features. Additionally, reduction of senescent cells lowered the levels of MMP13, which is purported to promote disc degenerative changes during aging. CONCLUSIONS:The findings of this study suggest that systemic reduction in the number of senescent cells ameliorates multiple age-associated changes within the disc tissue. Cellular senescence could therefore serve as a therapeutic target to restore the health of disc tissue that deteriorates with age.

60 APPLIED LIFE SCIENCES↗

Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

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

59 BASIC BIOLOGICAL SCIENCES↗

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

Environmental Molecular Sciences Laboratory↗

Energy Saving Melting and Revert Reduction Technology: Aging of Graphitic Cast Irons and Machinability

The objective of this task was to determine whether ductile iron and compacted graphite iron exhibit age strengthening to a statistically significant extent. Further, this effort identified the mechanism by which gray iron age strengthens and the mechanism by which age-strengthening improves the machinability of gray cast iron. These results were then used to determine whether age strengthening improves the machinability of ductile iron and compacted graphite iron alloys in order to develop a predictive model of alloy factor effects on age strengthening. The results of this work will lead to reduced section sizes, and corresponding weight and energy savings. Improved machinability will reduce scrap and enhance casting marketability. Technical Conclusions: Age strengthening was demonstrated to occur in gray iron ductile iron and compacted graphite iron. Machinability was demonstrated to be improved by age strengthening when free ferrite was present in the microstructure, but not in a fully pearlitic microstructure. Age strengthening only occurs when there is residual nitrogen in solid solution in the Ferrite, whether the ferrite is free ferrite or the ferrite lamellae within pearlite. Age strengthening can be accelerated by Mn at about 0.5% in excess of the Mn/S balance Estimated energy savings over ten years is 13.05 trillion BTU, based primarily on yield improvement and size reduction of castings for equivalent service. Also it is estimated that the heavy truck end use of lighter castings for equivalent service requirement will result in a diesel fuel energy savings of 131 trillion BTU over ten years.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

The Effect of Aging on the Delamination Fracture Energy of Glass Solar Reflectors

Thin metal and metal oxide films deposited on glass or polymer substrates have been widely applied to manufacture front surfaced solar reflectors such as those used in the concentrated solar power (CSP) systems due to the facts that they are highly transparent, resistant to ultraviolet (UV) light and abrasion, and chemically inert. However, the reliable operation over long periods of outdoor exposure of such solar reflectors depends on the adequate adhesion between each layer to prevent delamination and subsequent failure. We report results from measurements of the delamination fracture energy (DFE) of the weakest interface in both as-deposited and aged reflectors, where the reflector construction consists of a glass/copper/silver/oxide stack. In this study, DFE was measured using a width-tapered beam method and the test results showed that the weakest interface of this solar reflector is the copper-glass interface, with a delamination fracture energy of approximately 4.4 J/m 2 . In order to verify the test results, finite element (FE) simulations were run using the commercial software package ABAQUS 6.14 based on the cohesive zone model (CZM). In the simulations, the DFE derived from the delamination measurement was treated as an input and the delamination forces from the FE simulations were compared to the experimental results. The good agreement between the tested and simulated delamination force indicated that this width-tapered beam method is accurate even for very small DFE, making it appropriate to test the DFE of front surfaced glass solar reflectors. Additionally, in order to study the aging effect on the DFE, accelerated aging tests were conducted using samples with different protective coatings, one group of samples with alumina ( Al 2 O 3 ) protective coating and the other group with titania ( TiO 2 ) protective coating. The DFE after 50 and 100 hours of accelerated aging were measured. The test results showed that the copper-glass interface would still be the weakest interface for all samples after aging, and the DFE for samples with Al 2 O 3 protective coating was unchanged whereas the copper-glass interface was found to undergo statistically significant change after both 50 and 100 hours of aging for samples with TiO 2 protective coating. We found that DFE at the copper/glass interface decreased after 50 hours of aging then increased after 100 hours of aging. The origin of this non-monotonic response of TiO 2 coated reflectors under accelerated aging conditions is unknown.

36 MATERIALS SCIENCE↗

Advancing Multi-Hazard Risk and Safety Considerations for Aging Nuclear Facilities (Revision 1)

This project will demonstrate a multi-hazard time-dependent probabilistic risk assessment (PRA) approach for nuclear facilities considering aging-related deterioration of structures. A generic pressurized water reactor (PWR) reactor subjected to seismic mainshock-aftershock sequences considering the aging of the containment structure will be used as a case study to demonstrate the multi-hazard PRA approach. Using advanced modeling and simulation, seismic mainshock-aftershock fragility functions will be simulated for the containment structure considering aging effects. A multi-hazard PRA model for a generic PWR reactor will be built to quantify the multi-hazard core damage frequency (CDF) and large early release frequency (LERF) with explicit time-dependent modeling of event sequences. To date, the cascading impacts of multi-hazards are not adequately accounted for in the PRA models for nuclear facilities. In addition, for both initial and periodic evaluation of facilities to withstand natural phenomena hazards (NPH), deterioration of the SSCs due to aging and other effects is not adequately considered. By advancing multi-hazard considerations accounting for aging effects, this project will contribute to improved understanding of the safety of aging nuclear facilities. Project outcomes such as the multi-hazard CDF and LERF will also allow facility owners to optimize upgrade and retrofit protocols. This project is divided into two components: (1) advanced modeling and simulations; and (2) multi-hazard PRA. For the first component, Idaho National Laboratory’s (INL) Multi-hazard Analysis for STOchastic time-DOmaiN phenomena (MASTODON) and BlackBear codes will be used to simulate the seismic response and damage of a containment structure under cascading mainshock-aftershock sequences with aging effects. Uncertainties related to the seismic inputs, material parameters, and environmental factors such as temperature and humidity will be identified and propagated to the fragility functions. These fragility functions, which consider aging effects, will be time dependent. The second component will take the fragility information from the first component to build a multi-hazard time-dependent PRA model starting from a generic PWR model to evaluate the multi-hazard CDF and LERF and characterize the associated consequences. For this component, OpenPRA Web Application and SAPHIRE code will be used. Events such as the Fukushima Daiichi accident have highlighted the importance of considering the cascading impacts of multi-hazards for PRA. Moreover, many of the reactors in the current nuclear fleet in the United States (US) are already operating well beyond their initially planned design life, and applications for further extensions to operating licenses are being considered. Therefore, considering multi-hazard effects and aging deterioration in the NPH risk assessment process will contribute to the safety of both existing and future nuclear facilities. Outcomes of this project will thus directly benefit the standards DOE-STD-1020-16 and DOE-HDBK-1224-18.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Estimating the Ages of FGK Dwarf Stars through the Use of GALEX FUV Magnitudes

Stellar age cannot be directly measured, yet age determinations are fundamental to understanding the evolution of stars, planets, and galaxies. The work presented here builds upon the idea of a stellar-activity age. We utilized far-ultraviolet (FUV) photometry acquired by the Galaxy Evolution Explorer (GALEX) space telescope as an indicator of chromospheric activity to infer ages of late-F, G, and K type dwarf stars. We derived a purely empirical correlation between FUV magnitudes and stellar age in conjunction with (B − V) color. Our attention is restricted to Sun-like stars with color range 0.55⩽(B−V)⩽0.71 and absolute magnitude range 4.3 ≤ M {sub V} ≤ 5.3. The correlation is defined in terms of a FUV-excess parameter Q(FUV−B,B−V). We related stellar age, τ, to Q through the relation log{sub e}(τ)=log{sub e}(a)+bQ, where a and b are fit parameters and functions of (B − V). This correlation is functional up to 6 Gyr for FGK dwarfs. With such a correlation, one only needs Johnson (B − V) and FUV measurements to estimate the stellar age for Population i dwarf stars of solar-like temperature and metallicity. Such a calibration has utility in population studies of FGK dwarfs for further understanding of the chemical evolution of the Milky Way. As an illustration of one such application, we have constructed activity and FUV–age distributions for a sample of thin and thick disk stars, as distinguished by their chemical abundances. Considerable overlap is found between the activity distribution and age range of the two populations. We discuss the possibility that some high-[α/Fe] thick disk stars were formed as a result of the accretion of dwarf galaxies as recently as 4 Gyr ago.

79 ASTRONOMY AND ASTROPHYSICS↗

Aircraft observations of the chemical composition and aging of aerosol in the Manaus urban plume during GoAmazon 2014/5

Abstract. The Green Ocean Amazon (GoAmazon 2014/5) campaign, conducted from January 2014 to December 2015 in the vicinity of Manaus, Brazil, was designed to study the aerosol life cycle and aerosol–cloud interactions in both pristine and anthropogenically influenced conditions. As part of this campaign, the U.S. Department of Energy (DOE) Gulfstream 1 (G-1) research aircraft was deployed from 17 February to 25 March 2014 (wet season) and 6 September to 5 October 2014 (dry season) to investigate aerosol and cloud properties aloft. Here, we present results from the G-1 deployments focusing on measurements of the aerosol chemical composition and secondary organic aerosol (SOA) formation and aging. In the first portion of the paper, we provide an overview of the data and compare and contrast the data from the wet and dry season. Organic aerosol (OA) dominates the deployment-averaged chemical composition, comprising 80 % of the non-refractory PM1 aerosol mass, with sulfate comprising 14 %, nitrate 2 %, and ammonium 4 %. This product distribution was unchanged between seasons, despite the fact that total aerosol loading was significantly higher in the dry season and that regional and local biomass burning was a significant source of OA mass in the dry, but not wet, season. However, the OA was more oxidized in the dry season, with the median of the mean carbon oxidation state increasing from −0.45 in the wet season to −0.02 in the dry season. In the second portion of the paper, we discuss the evolution of the Manaus plume, focusing on 13 March 2014, one of the exemplary days in the wet season. On this flight, we observe a clear increase in OA concentrations in the Manaus plume relative to the background. As the plume is transported downwind and ages, we observe dynamic changes in the OA. The mean carbon oxidation state of the OA increases from −0.6 to −0.45 during the 4–5 h of photochemical aging. Hydrocarbon-like organic aerosol (HOA) mass is lost, with ΔHOA∕ΔCO values decreasing from 17.6 µg m−3 ppmv−1 over Manaus to 10.6 µg m−3 ppmv−1 95 km downwind. Loss of HOA is balanced out by formation of oxygenated organic aerosol (OOA), with ΔOOA∕ΔCO increasing from 9.2 to 23.1 µg m−3 ppmv−1. Because hydrocarbon-like organic aerosol (HOA) loss is balanced by OOA formation, we observe little change in the net Δorg∕ΔCO values; Δorg∕ΔCO averages 31 µg m−3 ppmv−1 and does not increase with aging. Analysis of the Manaus plume evolution using data from two additional flights in the wet season showed similar trends in Δorg∕ΔCO to the 13 March flight; Δorg∕ΔCO values averaged 34 µg m−3 ppmv−1 and showed little change over 4–6.5 h of aging. Our observation of constant Δorg∕ΔCO are in contrast to literature studies of the outflow of several North American cities, which report significant increases in Δorg∕ΔCO for the first day of plume aging. These observations suggest that SOA formation in the Manaus plume occurs, at least in part, by a different mechanism than observed in urban outflow plumes in most other literature studies. Constant Δorg∕ΔCO with plume aging has been observed in many biomass burning plumes, but we are unaware of reports of fresh urban emissions aging in this manner. These observations show that urban pollution emitted from Manaus in the wet season forms less particulate downwind as it ages than urban pollution emitted from North American cities.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Three ages of Venus

A central question for any planet is the age of its surface. Based on comparative planetological arguments, Venus should be as young and active as the Earth (Wood and Francis). The detection of probable impact craters in the Venera radar images provides a tool for estimating the age of the surface of Venus. Assuming somewhat different crater production rates, Bazilevskiy et al. derived an age of 1 + or - 0.5 billion years, and Schaber et al. and Wood and Francis estimated an age of 200 to 400 million years. The known impact craters are not randomly distributed, however, thus some area must be older and others younger than this average age. Ages were derived for major geologic units on Venus using the Soviet catalog of impact craters (Bazilevskiy et al.), and the most accessible geologic unit map (Bazilevskiy). The crater counts are presented for (diameters greater than 20 km), areas, and crater densities for the 7 terrain units and coronae. The procedure for examining the distribution of craters is superior to the purely statistical approaches of Bazilevskiy et al. and Plaut and Arvidson because the bins are larger (average size 16 x 10(6) sq km) and geologically significant. Crater densities define three distinct groups: relatively heavily cratered (Lakshmi, mountain belts), moderately cratered (smooth and rolling plains, ridge belts, and tesserae), and essentially uncratered (coronae and domed uplands). Following Schaber et al., Grieve's terrestrial cratering rate of 5.4 + or - 2.7 craters greater than 20 km/10(9) yrs/10(6) sq km was used to calculate ages for the geologic units on Venus. To improve statistics, the data was aggregated into the three crater density groups, deriving the ages. For convenience, the three similar age groups are given informal time stratigraphic unit names, from youngest to oldest: Ulfrunian, Sednaian, Lakshmian.

Wood, Charles A.↗

Ar-39-Ar-40 ages of four ureilites

Ureilites Novo Urei, Havero, and Kenna show strong evidence of one or more Ar-40 degassing events in the time period of 3.3-4.1 Ga ago. These ages may be compared to current interpretations of ureilite chronology. These include the suggestion of metasomatic activity on the parent body 3.7 Ga ago that reset some Sm-Nd ages and the suggestion that ureilites have experienced terrestrial contamination of several trace elements (including Pb and LREE), which makes suspect ages younger than approximately 4.5 Ga. Because the K-Ar chronometer can be sensitive to metamorphic events, we made Ar-39-Ar-40 determinations on bulk samples (0.12-0.14 g each) of four ureilites. The Ar-39-Ar-40 age spectra and K/Ca ratios as a function of cumulative Ar release from stepwise temperature extractions for the four ureilites analyzed are shown. Because Ar-39-Ar-40 ages shown by low and high temperature extractions may be suspect, we examined the intermediate temperature extractions. Although interpretation of these spectra is obviously uncertain, we believe that the most recent times of Ar degassing can be roughly inferred. These times are approximately 3.3 Ga for Havero, 3.3-3.7 Ga for Novo Urei, and approximately 4.1 Ga for Kenna, for which Ar degassing may not have been complete. The indication of Ar-39-Ar-40 degassing ages of 3.3-4.1 Ga for three ureilites that also contain an enhanced LREE component and (excepting Havero) produce a 3.74 Ga Sm-Nd age, suggests that both chronometers may have responded to the same parent body event. On the other hand, it is also possible that the Ar data reflect one or more separate events that did not strongly affect the Sm-Nd system, a situation that commonly occurs in eucrites. Thus the existence of reset Ar ages does not require similarly reset Sm-Nd ages.

Bogard, D. D.↗

Synergistic Effects of Physical Aging and Damage on Long-Term Behavior of Polymer Matrix Composites

The research consisted of two major parts, first modeling and simulation of the combined effects of aging and damage on polymer composites and secondly an experimental phase examining composite response at elevated temperatures, again activating both aging and damage. For the simulation, a damage model for polymeric composite laminates operating at elevated temperatures was developed. Viscoelastic behavior of the material is accounted for via the correspondence principle and a variational approach is adopted to compute the temporal stresses within the laminate. Also, the effect of physical aging on ply level stress and on overall laminate behavior is included. An important feature of the model is that damage evolution predictions for viscoelastic laminates can be made. This allows us to track the mechanical response of the laminate up to large load levels though within the confines of linear viscoelastic constitutive behavior. An experimental investigation of microcracking and physical aging effects in polymer matrix composites was also pursued. The goal of the study was to assess the impact of aging on damage accumulation, in ten-ns of microcracking, and the impact of damage on aging and viscoelastic behavior. The testing was performed both at room and elevated temperatures on [+/- 45/903](sub s) and [02/903](sub s) laminates, both containing a set of 90 deg plies centrally located to facilitate investigation of microcracking. Edge replication and X-ray-radiography were utilized to quantify damage. Sequenced creep tests were performed to characterize viscoelastic and aging parameters. Results indicate that while the aging times studied have limited ]Influence on damage evolution, elevated temperature and viscoelastic effects have a profound effect on the damage mode seen. Some results are counterintuitive, including the lower strain to failure for elevated temperature tests and the catastrophic failure mode observed for the [+/- 45/9O3](sub s), specimens. The fracture toughness for transverse cracks increases with increasing temperature for both systems: transverse cracking was completely absent prior to failure in [+/- 45/903](sub s), and was suppressed for [02/903](sub s). No significant effect of damage on aging or viscoelastic parameters was observed.

Brinson, L. Cate↗

Mineralogy, Petrology, Chemistry, and Ar-39 - Ar-40 and Ages of the Caddo County IAB Iron: Evidence for Early Partial Melt Segregation of a Gabbro Area Rich in Plagioclase-Diopside

We found coarse-grained gabbroic material rich in plagioclase and diopside in the Caddo County IAB iron meteorite. The polished thin sections studied were made from areas rich in Al and Ca detected by a micro-focus X-ray fluorescence (XRF) mapping technique. The gabbro is not a clast within a breccia, but rather this area is located mainly at silicate-metal boundaries only a few cm away from an area with fine-grained, ultramafic silicate similar to winonaites. Medium-grained orthopyroxene and olivine are found in transitional areas showing no disturbance of their crystalline textures. A vein-like region, starting at the area rich in fine-grained mafic silicate, extends towards the gabbroic area with a gradual increase in abundance of plagioclase and diopside. This texture and our accumulated knowledge of the formation mechanism of IAB/winonaltes meteorites, suggest that the gabbroic materials were formed by inhomogeneous segregation of partial melts of chondritic source materials. Compositional data on two mineralogically distinct samples of the gabbro-rich portion of the inclusion were obtained by INAA. Compared to an average of LAB silicate inclusions or winonaites, the Caddo County gabbro is enriched in the incompatible lithophile elements Na, Ca, Sc, REE and Hf, which is consistent with a melt origin for the gabbro. The cosmogenic space exposure age of Caddo County (511 Ma) is significantly younger than exposure ages of some other IAB meteorites, An 39Ar-40Ar age determination of the gabbroic material indicates a series of upward steps in age from 4.516 Ga to 4.523 Ga, with a few high temperature ages up to 4.54 Ga. The older age could approximate the primary recrystallization age of silicates. The stepped Ar age spectrum may indicate differences in Ar closure temperatures during slow cooling of -2-20'C/Myr in the parent body. Alternatively, the younger Ar-Ar ages may date a shock event which occurred while Caddo County was hot and which also created textures such as a linear metal vein with rounded zigzag walls in a diopside crystal and slightly miss-oriented rounded plagioclase domain.

Takeda, Hiroshi↗

Aging Theories for Establishing Safe Life Spans of Airborne Critical Structural Components

New aging theories have been developed to establish the safe life span of airborne critical structural components such as B-52B aircraft pylon hooks for carrying air-launch drop-test vehicles. The new aging theories use the equivalent-constant-amplitude loading spectrum to represent the actual random loading spectrum with the same damaging effect. The crack growth due to random loading cycling of the first flight is calculated using the half-cycle theory, and then extrapolated to all the crack growths of the subsequent flights. The predictions of the new aging theories (finite difference aging theory and closed-form aging theory) are compared with the classical flight-test life theory and the previously developed Ko first- and Ko second-order aging theories. The new aging theories predict the number of safe flights as considerably lower than that predicted by the classical aging theory, and slightly lower than those predicted by the Ko first- and Ko second-order aging theories due to the inclusion of all the higher order terms.

Ko, William L.↗

Re-Evaluation of Ar-39 - Ar-40 Ages for Apollo Lunar Rocks 15415 and 60015

We re-analyzed 39Ar-40Ar ages of Apollo lunar highland samples 15415 and 60015, two ferroan anorthosites analyzed previously in the 1970 s, with a more detailed approach and with revised decay constants. From these samples we carefully prepared 100-200 mesh mineral separates for analysis at the Noble Gas Laboratory at NASA-Johnson Space Center. The Ar-39-Ar-40 age spectra for 15415 yielded an age of 3851 +/- 38 Ma with 33-99% of Ar39 release, roughly in agreement with previously reported Ar-Ar ages. For 60015, we obtained an age of 3584 +/- 152 Ma in 23-98% of Ar39 release, also in agreement with previously reported Ar-Ar ages of approximately 3.5 Ga. Highland anorthosites like these are believed by many to be the original crust of the moon, formed by plagioclase floatation atop a magma ocean, however the Ar-Ar ages of 15415 and 60015 are considerably younger than lunar crust formation. By contrast, recently recovered lunar anorthosites such as Dhofar 489, Dhofar 908, and Yamato 86032 yield older Ar-Ar ages, up to 4.35 Ga, much closer to time of formation of the lunar crust. It follows that the Ar-Ar ages of the Apollo samples must have been reset by secondary heating, and that this heating affected highland anorthosites at both the Apollo 15 and Apollo 16 landing sites but did not affect lunar highland meteorites. One obvious consideration is that while the Apollo samples were collected from the near side of the moon, these lunar meteorites are thought to have originated from the lunar far side

Park, J.↗

Brain Aging Hallmarks: A Primer for Future Studies on Space Radiation Effects

As humankind endeavors to travel farther away from Earth, many questions remain to be solved to ensure proper preparation for deep space. Multiple spaceflight stressors can elicit adverse health outcomes including exposure to space radiation. Space radiation exposure has been identified by the National Aeronautics and Space Administration (NASA) as an important contributor to cancer, degenerative tissue diseases including cataracts, cardiovascular disease, immune system dysfunction and possible central nervous system decrements. The complexity of the human central nervous system makes it difficult to adequately recapitulate in experimental model systems, which hinders quantitative description of associated decrements. The brain aging hallmarks, as introduced by Mattson and Arumugam in 2018, are measurable cellular and molecular hallmarks that generally contribute to the aging process, describe an aging phenotype, and are part of the etiology of age-related neurodegenerative diseases. These hallmarks include mitochondrial dysfunction, accumulation of oxidatively damaged molecules (oxidative stress), impaired lysosome and proteasome function, dysregulation of neuronal calcium homeostasis, compromised adaptive cellular stress response, aberrant neuronal network activity, impaired deoxyribonucleic acid (DNA) repair, inflammation, impaired neurogenesis and dysregulated energy metabolism. Cellular senescence and telomere attrition may also be considered, though more evidence is needed to regard them as brain-specific hallmarks of aging. Radiation exposure has previously been correlated with aging etiology; therefore, investigating the effects of radiation exposure within the context of the hallmarks of brain aging may provide insights into potential health risks facing NASA astronauts, and may provide a means to identify disease processes that may be important targets for disease prevention or intervention. This work describes the hallmarks of brain aging and serves as a primer for future investigation into how the hallmarks of brain aging may compare and contrast with outcomes associated with exposure to the space radiation environment. Further, it will be useful in future identification of hallmarks that may be appropriate to target for radiation countermeasures specific to the central nervous system.

Vivian Lu↗

US/UK second level panel discussions on the health and value of: Ageing and lifetime predictions (u)

Many healthy physics, engineering, and materials exchanges are being accomplished in ageing and lifetime prediction that directly supports US and UK Stockpile Management Programs. Lifetime assessment studies of silicon foams under compression - Joint AWE/LANLlLLNL study of compression set in stress cushions completed. Provides phenomenological prediction out to 50 years. Polymer volatile out-gassing studies - New exchange on the out-gassing of Ethylene Vinyl Acetate (EVA) using isotopic {sup 13}C labeling studies to interrogate mechanistic processes. Infra-red (IR) gas cell analytical capabilities developed by AWE will be used to monitor polymer out-gassing profiles. Pu Strength ageing Experiments and Constitutive Modeling - In recently compared modeling strategies for ageing effects on Pu yield strength at high strain rates, a US/UK consensus was reached on the general principle that the ageing effect is additive and not multiplicative. The fundamental mechanisms for age-strengthening in Pu remains unknown. Pu Surface and Interface Reactions - (1) US/UK secondment resulted in developing a metal-metal oxide model for radiation damaged studies consistent with a Modified Embedded Atom Method (MEAM) potential; and (2) Joint US/UK collaboration to study the role of impurities in hydride initiation. Detonator Ageing (wide range of activities) - (1) Long-term ageing study with field trials at Pantex incorporating materials from LANL, LLNL, SNL and AWE; (2) Characterization of PETN growth to detonation process; (3) Detonator performance modeling; and (4) Performance fault tree analysis. Benefits are a unified approach to lifetime prediction that Includes: materials characterization and the development of ageing models through improved understanding of the relationship between materials properties, ageing properties and detonator performance.

36 MATERIALS SCIENCE↗

BENCHMARK ACCELERATED AGING OF HARVESTED HYPALON/EPR AND CSPE/XLPE POWER AND I&C CABLE IN NUCLEAR POWER PLANTS

As part of the Light Water Reactor and Sustainability (LWRS) program in the U.S. Department of Energy (DOE) Office of Nuclear Energy, material aging and degradation research is currently geared to support the long-term operation of existing nuclear power plants (NPPs) as they move beyond their initial 40 year licenses. The goal of this research is to provide information so that NPPs can develop aging management programs (AMPs) to address replacement and monitoring needs as they look to operate for 20 years, and in some cases 40 years, beyond their initial operating lifetimes. For cable insulation and jacket materials that support instrument, control, and safety systems, accelerated aging data are needed to determine priorities in cable aging management programs. Before accelerated thermal and radiation aging of harvested, representative cable insulation and jacket materials, the benchmark performance of a new test capability at Oak Ridge National Laboratory (ORNL) was evaluated for temperatures between 70 and 135 C, dose rates between 100 and 500 Gy/h, and accumulated doses up to 20 kGy, Samples that were characterized and are representative of current materials in use were harvested from the Callaway NPP near Fulton, Missouri, and the San Onofre NPP north of San Diego, California. From the Callaway NPP, a multiconductor control rod cable manufactured by Boston Insulated Wire (BIW), with a Hypalon/ chorolosulfonated polyethylene (CSPE) jacket and ethylene-propylene rubber (EPR) insulation, was harvested from the auxiliary space during a planned outage in 2013. This cable was placed into service when the plant was started in 1984. From the San Onofre NPP, a Rockbestos Firewall III (FRIII) cable with a Hypalon/ CSPE jacket with cross-linked polyethylene (XLPE) insulation was harvested from an on-site, climate-controlled storage area. This conductor, which was never placed into service, was procured around 2007 in anticipation of future operation that did not occur. Benchmark aging for both jacket and insulation material was carried out in air at a temperature of 125 C or in uniform 140 Gy/h gamma irradiation over a period of 60 days. Their mechanical properties over the course of their exposures were compared with reference data from comparable cable jacket/insulation compositions and aging conditions. For both accelerated thermal and radiation aging, it was observed that the mechanical properties for the Callaway BIW control rod cable were consistent with those previously measured. However, for the San Onofre Rockbestos FRIII, there was an observable functional difference for accelerated thermal aging at 125 C. Details on possible sources for this difference and plans for resolving each source are given in this paper.

Duckworth, Robert C↗