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DOE OSTI2021

Breast-Specific Molecular Clocks Comprised of ELF5 Expression and Promoter Methylation Identify Individuals Susceptible to Cancer Initiation

A robust breast cancer prevention strategy requires risk assessment biomarkers for early detection. We show that expression of ELF5, a transcription factor critical for normal mammary development, is downregulated in mammary luminal epithelia with age. DNA methylation of the ELF5 promoter is negatively correlated with expression in an age-dependent manner. Both ELF5 methylation and gene expression were used to build biological clocks to estimate chronological ages of mammary epithelia. ELF5 clock-based estimates of biological age in luminal epithelia from average-risk women were within three years of chronological age. Biological ages of breast epithelia from BRCA1 or BRCA2 mutation carriers, who were high risk for developing breast cancer, suggested they were accelerated by two decades relative to chronological age. The ELF5 DNA methylation clock had better performance at predicting biological age in luminal epithelial cells as compared with two other epigenetic clocks based on whole tissues. We propose that the changes in ELF5 expression or ELF5-proximal DNA methylation in luminal epithelia are emergent properties of at-risk breast tissue and constitute breast-specific biological clocks.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

A study of degradation mechanisms in PVDF-based photovoltaic backsheets

Abstract Commercial backsheets based on polyvinylidene fluoride (PVDF) can experience premature field failures in the form of outer layer cracking. This work seeks to provide a better understanding of the changes in material properties that lead to crack formation and find appropriate accelerated tests to replicate them. The PVDF-based backsheet outer layer can have a different structure and composition, and is often blended with a poly(methyl methacrylate) (PMMA) polymer. We observed depletion of PMMA upon aging with sequential (MAST) and combined (C-AST) accelerated stress testing. In field-aged samples from Arizona and India, where PVDF crystallizes in its predominant α-phase, the degree of crystallinity greatly increased. MAST and C-AST protocols were, to some extent, able to replicate the increase in crystallinity seen in PVDF after ~ 7 years in the field, but no single-stress test condition (UV, damp heat, thermal cycling) resulted in significant changes in the material properties. The MAST regimen used here was too extreme to produce realistic degradation, but the test was useful in discovering weaknesses of the particular PVDF-based outer layer structure studied. No excessive β-phase formation was observed after aging with any test condition; however, the presence of β-phase was identified locally by Fourier transform infrared spectroscopy (FTIR). We conclude that both MAST and C-AST are relevant tests for screening outdoor failure mechanisms in PVDF backsheets, as they were successful in producing material degradation that led to cracking.

14 SOLAR ENERGY↗

DOE OSTI2022

A 500 KV INVERTED GEOEMTRY FEEDTHROUGH FOR A HIGH VOLT-AGE DC ELECTRON GUN

The Continuous Electron Beam Accelerator Facility injector at Jefferson Lab (JLab) utilizes an inverted-geometry ceramic insulator photogun operating at 130 kV direct current to generate spin-polarized electron beams for high-energy nuclear physics experiments. A second photogun delivers 180 keV beam for commissioning a SRF booster in a testbed accelerator, and a larger version delivers 300 keV magnetized beam in a test stand beam line. This contribution reports on the development of an unprecedented inverted-insulator with cable connector for reliably applying 500 kV DC to a future polarized beam photogun, to be designed for operating at 350 kV without field emission. Such a photogun design could then be used for generating a polarized electron beam to drive a spin-polarized positron source as a demonstrator for high energy nuclear physics at JLab. There are no commercial cable connectors that fit the large inverted insulators required for that voltage range. Our proposed concept is based on a modified epoxy receptacle with intervening SF6 layer and a test electrode in a vacuum vessel.

Hernandez-Garcia, C.↗

DOE OSTI2021

Extremum Seeking-Based Control System for Particle Accelerator Beam Loss Minimization

Particle accelerators throughout the world vary widely in terms of age and availability of advanced noninvasive diagnostics that provide varying levels of detail about the accelerated beams. Additionally, beam loss measurements and current monitors are ubiquitous in the accelerator community, they are noninvasive, and they are some of the most important metrics in terms of preventing damage or irradiation of beam pipes and equipment for high-energy machines. However, beam loss and current measurements are difficult to use for feedback tuning because of a lack of a known analytic relationship between scalar loss measurements throughout an accelerator and the hundreds of thousands of parameters that influence the beam and time variation of the beam source itself. In this work, we present a model-independent extremum seeking (ES) controller, which has been implemented for automated tuning and optimization of the Los Alamos Neutron Science Center (LANSCE) linear ion accelerator based only on scalar quantities, such as beam loss or flux measurements. We demonstrate the approach on various accelerator subsystems, including groups of radio frequency (RF) accelerating cavities, quadrupole magnets, bending magnets, and steering magnets. This tool is now available as a use graphical user interface (GUI) in the LANSCE control room, allowing beam physicists to choose arbitrary groups of parameters and beam loss or current monitors for adaptive tuning.

43 PARTICLE ACCELERATORS↗

DOE OSTI2024

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo

Background: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. Methods: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. Results: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. Conclusions: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Reviving the carbon sink: The influence of moderate wind disturbance in a secondary temperate mixed forest

Global forests are increasingly exposed to climate-driven perturbations, which may in turn alter their climate mitigation potential. As tropical cyclones expand poleward due to climate warming, wind disturbances in temperate forests have become increasingly frequent. The consequences of moderate wind disturbances remain poorly understood, hindering efforts to quantify their role in the global carbon cycle. Here, we used 16 years of continuous eddy covariance and biometric measurements to investigate the impacts of moderate wind disturbances on the structure and carbon sink dynamics of a temperate forest in Northeast China. Following Typhoon Maysak in 2020, the mortality of large trees (particularly the aging pioneer species) increased ninefold, whereas that of small trees decreased by nearly half. Both stand basal area and leaf area index were reduced between 2019 and 2023, with aging pioneer tree species being more vulnerable than mid-to-late species to wind disturbances. Shifts in species composition altered the environmental sensitivity of forest carbon sink function. Unexpectedly, wind disturbances reversed the declining trends in net ecosystem production and ecosystem carbon use efficiency of this secondary forest. A novel composite structural indicator—the standardized leaf area index (the maximum leaf area supported by per basal area of the stand)—provided robust predictions (R 2 > 0.4) of carbon sink dynamics throughout the study period. The selective removal of less efficient pioneer trees accelerated succession and reversed the aging-related decline in forest carbon sink strength and carbon use efficiency. In conclusion, these findings highlight the potential role of moderate wind disturbances in enhancing forest carbon sink function and offer a framework for understanding, assessing, and predicting forest carbon dynamics under increasing disturbance frequencies driven by climate change.

Carbon sink↗

NASA NTRS2012

Long-Term Changes in Stratospheric Age Spectra in the 21st Century in the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM)

In this study we investigate the long-term variations in the stratospheric age spectra using simulations of the 21st century with the Goddard Earth Observing System Chemistry- Climate Model (GEOSCCM). Our purposes are to characterize the long-term changes in the age spectra and identify processes that cause the decrease of the mean age in a warming climate. Changes in the age spectra in the 21st century simulations are characterized by decreases in the modal age, the mean age, the spectral width, and the tail decay timescale. Our analyses show that the decrease in the mean age is caused by two processes: the acceleration of the residual circulation that increases the young air masses in the stratosphere, and the weakening of the recirculation that leads to the decrease of tail of the age spectra and the decrease of the old air masses. The weakening of the stratospheric recirculation is also strongly correlated with the increase of the residual circulation. One important result of this study is that the decrease of the tail of the age spectra makes an important contribution to the decrease of the main age. Long-term changes in the stratospheric isentropic mixing are investigated. Mixing increases in the subtropical lower stratosphere, but its impact on the age spectra is outweighed by the increase of the residual circulation. The impacts of the long-term changes in the age spectra on long-lived chemical traces are also investigated. 37 2

Li, Feng↗

NASA NTRS1992

Constraints on the acceleration of anomalous cosmic rays

The recent determination of an upper limit of 0.2 pc on the distance to the source of the anomalous cosmic rays, and the implied upper limit on their age imposes a significant observational constraint on possible acceleration mechanisms. Adiabatic cooling in the expanding wind makes the constraints significantly more stringent. In the light of these constraints, the rate of second-order Fermi acceleration is much too low to play a significant role. Diffusive shock acceleration, even at the strong termination shock of the solar wind, is sufficient only if one discards the standard expression for the maximum acceleration rate based on the Bohm limit. Only diffusive acceleration at the quasi-perpendicular solar wind termination shock has a high enough acceleration rate to be the source of the anomalous component.

Jokipii, J. R.↗

DOE OSTI2020

Mapping of Heterogeneous Catalyst Degradation in Polymer Electrolyte Fuel Cells

Pt catalysts in polymer electrolyte fuel cells degrade heterogeneously as the catalyst particles are exposed to local variations throughout the catalyst layer during operation. State-of-the-art analytical techniques for studying degradation of Pt catalysts do not possess fine spatial resolution to elucidate such non-uniform degradation behavior at a large electrode level. A new methodology is developed to spatially resolve and quantify the heterogeneous Pt catalyst degradation over a large area (several cm ) of aged MEAs based on synchrotron X-ray microdiffraction. PEFC single cells are aged using voltage cycling as an accelerated stress test and the degradation heterogeneity at a micrometer length scale is visualized by mapping Pt catalyst particle size after voltage cycling. It is demonstrated in detail that the Pt catalyst particle size growth is non-uniform and follows the flow field geometry. The Pt particle size growth is greater in the area under the flow field land, while it is minimal in the area under the flow field channel. Additional non-uniformity is observed with the Pt particle size increasing more rapidly at the air outlet area than the Pt particle size at the inlet area.

36 MATERIALS SCIENCE↗

NASA NTRS1979

Resin/fiber thermo-oxidative interactions in PMR polymide/graphite composites

The amounts of resin weight loss and fiber weight loss in four PMR-polyimide graphite fiber composites were calculated from the composite weight losses and the fiber/resin ratios of the composites after long term thermo-oxidative aging in 600 F air. The accelerating effect of graphite fiber on resin weight loss, compared to neat resin weight loss, indicated the presence of a deleterious resin/fiber thermo-oxidative interaction, presumably due to fiber impurities. Similarly, the decelerating effect of the protective matrix resin on fiber weight loss, compared to bare fiber weight loss, was also demonstrated. The amount of hydrazine-indigestible resin and the amount of loose surface graphite fiber that formed during 600 deg F exposure of the composites were quantitatively determined. The indigestible residual resin was also qualitatively studied by scanning electron microscopy.

Alston, W. B.↗

NASA NTRS1995

Chemical studies of H chondrites. 5: Temporal variations of sources

We report Cl-36 (301-kyr half-life) data obtained by accelerator mass spectrometry allowing nominal terrestrial ages to be determined for 39 Antarctic H4-6 chondrites for which contents of volatile trace elements are known. The compositional difference between these Antarctic meteorites and 58 non-Antarctic falls increases with terrestrial age and, using multivariate statistical techniques, becomes highly significant for Antarctic samples with ages greater than 50 kyr. The compositional difference is inconsistent with trivial causes such as weathering and seems to reflect differences in thermal histories of parent sources. Temporal source variations for the H chondrite flux on Earth thus exist not only on a short-term, 40 years, basis (Dodd et al., 1993) but also on a long-term, greater than 50 kyr, basis.

Michlovich, Edward S.↗

NASA NTRS2000

Parabolic flight reveals independent binocular control of otolith-induced eye torsion

To examine otolith-governed ocular torsion in hyper- and hypogravity, eight subjects, including two astronauts, underwent parabolic flight while seated upright with head fixed. A mask fitted with two video cameras provided synchronized images of both eyes at a rate of 25/sec during 15 parabolas, the individual parabolas separated by a few minutes of level 1 G flight. Three main findings emerged: 1) After the first parabola, most subjects showed differential torsional offset of the two eyes in the 1 G portions between parabolas, compared to the conjugate baseline position of the eyes prior to the first parabola. 2) Changes in binocular torsion in the 0 G and 1.8 G portions of parabolic flight revealed in most subjects systematic reversal of direction. The reversal was consistent within, but not across subjects. 3) Disconjugacy defined as the moment-to-moment difference in the movements of the two eyes, and evaluated without the contribution of the differential offset, found two subjects with relatively high disconjugacy scores, and the remaining six with low scores. On the basis of prior studies (9, 20), we would predict the first two would be subject to SMS, the remainder not. The two astronauts, who did not have SMS on their space missions, fell into the low scoring group. We propose that the disconjugacies may be due to intrinsic asymmetries in the otolith receptors on the two sides of the head, which appear to be independently linked to the extraocular muscles of the two eyes, a phenomenon masked in normal 1 G states by adaptation. The apparently independent control of the two sides cannot be detected by the simpler and more common monocular studies.

Non-NASA Center↗

DOE OSTI2021

Applying laboratory methods for durability assessment of vitrified material to archaeological samples

Abstract Laboratory testing used to assess the long-term chemical durability of nuclear waste forms may not be applicable to disposal because the accelerated conditions may not represent disposal conditions. To address this, we examine the corrosion of vitrified archeological materials excavated from the near surface of a ~1500-year old Iron Age Swedish hillfort, Broborg, as an analog for the disposal of vitrified nuclear waste. We compare characterized site samples with corrosion characteristics generated by standard laboratory durability test methods including the product consistency test (PCT), the vapor hydration test (VHT), and the EPA Method 1313 test. Results show that the surficial layer of the Broborg samples resulting from VHT displays some similarities to the morphology of the surficial layer formed over longer timescales in the environment. This work provides improved understanding of long-term glass corrosion behavior in terms of the thickness, morphology, and chemistry of the surficial features that are formed.

36 MATERIALS SCIENCE↗

DOE OSTI2022

Operation of the H- Linac at FNAL

The Fermi National Accelerator Laboratory (FNAL) Linac has been in operation for 52 years. In approximately four years, it will be replaced by a new 800 MeV superconducting machine, the PIP-II SRF Linac. In the current configuration, the Linac delivers H- ions at 400 MeV and injects protons by charge exchange into the Booster synchrotron. Despite its age, the Linac is the most stable accelerator in the FNAL complex, reliably sending 22 mA in daily operations. We will discuss the status of the operation, beam studies, and plans.

43 PARTICLE ACCELERATORS↗

NASA NTRS1976

Effect of hypovolemia, infusion, and oral rehydration on gradual onset +Gz acceleration tolerance

The purpose of this study was to determine the effect of blood withdrawal, blood infusion, and oral fluid intake on +Gz tolerance at an acceleration rate of 0.5 G/min. Six healthy men aged 21-27 yr were centrifuged after the withdrawal of 400 ml of blood (hypovolemia) from each man; they were centrifuged again following blood infusion (Phase I). Three weeks later the men were accelerated after similar hypovolemia and again after consuming 800 ml of an isotonic NaCl drink (Phase II). Phase I hypovolemia resulted in a reduction in tolerance in all subjects from a mean control level of 6.42 + or - 0.35 min to 5.45 + or - 0.17 min (-15.1%, p less than 0.05). Both infusion and drinking returned tolerances to control levels. During acceleration there were significant (p less than 0.05) increases in plasma vasopressin levels to 35 pg/ml; these were not influenced appreciably by infusion or drinking. In all acceleration runs there was an obligatory shift (loss) of plasma volume and electrolytes, especially potassium, regardless of the experimental treatments. Oral rehydration is shown to be as effective as blood replacement in restoring +Gz acceleration tolerance decrements due to hypovolemia.

Greenleaf, J. E.↗

DOE OSTI2023

Concepts of association between cancer and ionising radiation: accounting for specific biological mechanisms

The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2026

Dynamic Nanoscale Spatial Heterogeneity in a Perovskite-to-Brownmillerite Topotactic Phase Transformation

Phase transitions are omnipresent in modern condensed matter physics and its applications. In solids, first-order phase transformations typically occur by nucleation and growth under nonequilibrium conditions. Under constant external conditions, e.g., constant annealing temperature and pressure, the nucleation and growth dynamics are often thought of as spatially and temporally independent. Here, in situ Bragg X-ray photon correlation spectroscopy (XPCS) reveals nanoscale spatial and dynamical heterogeneity in the perovskite-to-brownmillerite topotactic phase transformation in La 0.7 Sr 0.3 CoO 3 thin films annealed under constant reducing conditions over a time span of multiple hours. Specifically, a time scale associated with domain growth remains stable, with a corresponding domain wall speed of v d = 6 ± 0.5 × 10 –4 nm/s (2 ± 0.2 nm/h), while a slower time scale, associated with temperature-driven depinning of domains, leads to accelerating dynamics with time scales following an aging power law with exponent −2.2 ± 0.5. This experiment demonstrates that Bragg XPCS is a powerful tool to study nanoscale dynamics in structural phase transformations, with the ability to extract quantitative average values related to nanodomain motion in situ. Furthermore, the results are relevant for phase engineering of phase-change devices, as they show that nanoscale dynamics, linked to domain and domain-wall motion, can continuously evolve and speed up with time, even hours after the initiation of the phase transformation, with potential repercussions on electrical performance.

X-ray photon correlation spectroscopy↗

NASA NTRS1977

Fluid and electrolyte shifts in women during +Gz acceleration after 15 days' bed rest

Experiments were conducted on twelve women aged 23-34 yr - a bed rest (BR) group of eight subjects and an ambulatory (AMB) group of four subjects - to determine the effect of bed rest on shifts in plasma volume, electrolytes, and erythrocyte volume during +Gz acceleration on a centrifuge. The BR group underwent the +Gz acceleration during a two-week ambulatory control period, after 15 days of a 17-day BR period, and on the third day of ambulatory recovery. The AMB group underwent the same experimental procedures, but continued their normal daily routine during the BR period without additional prescribed physical exercise. Major conclusions are that (1) the higher the mean control tolerance, the greater the tolerance decline after BR; (2) relative confinement and reduced activity contribute as much to reduction in tolerance as does the horizontal body position during BR; (3) BR deconditioning has no effect on the erythrocyte volume during +3.0 Gz; and (4) about one-half the loss in tolerance after BR can be attributed to plasma volume and electrolyte shifts.

Greenleaf, J. E.↗