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At least 1,387 records · Page 77
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Combining pairwise structural similarity and deep learning interface contact prediction to estimate protein complex model accuracy in CASP15

Abstract Estimating the accuracy of quaternary structural models of protein complexes and assemblies (EMA) is important for predicting quaternary structures and applying them to studying protein function and interaction. The pairwise similarity between structural models is proven useful for estimating the quality of protein tertiary structural models, but it has been rarely applied to predicting the quality of quaternary structural models. Moreover, the pairwise similarity approach often fails when many structural models are of low quality and similar to each other. To address the gap, we developed a hybrid method (MULTICOM_qa) combining a pairwise similarity score (PSS) and an interface contact probability score (ICPS) based on the deep learning inter‐chain contact prediction for estimating protein complex model accuracy. It blindly participated in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 and performed very well in estimating the global structure accuracy of assembly models. The average per‐target correlation coefficient between the model quality scores predicted by MULTICOM_qa and the true quality scores of the models of CASP15 assembly targets is 0.66. The average per‐target ranking loss in using the predicted quality scores to rank the models is 0.14. It was able to select good models for most targets. Moreover, several key factors (i.e., target difficulty, model sampling difficulty, skewness of model quality, and similarity between good/bad models) for EMA are identified and analyzed. The results demonstrate that combining the multi‐model method (PSS) with the complementary single‐model method (ICPS) is a promising approach to EMA.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Path integral Monte Carlo simulations of H{sub 2} adsorbed to lithium-doped benzene: A model for hydrogen storage materials

Finite temperature quantum and anharmonic effects are studied in H{sub 2}–Li{sup +}-benzene, a model hydrogen storage material, using path integral Monte Carlo (PIMC) simulations on an interpolated potential energy surface refined over the eight intermolecular degrees of freedom based upon M05-2X/6-311+G(2df,p) density functional theory calculations. Rigid-body PIMC simulations are performed at temperatures ranging from 77 K to 150 K, producing both quantum and classical probability density histograms describing the adsorbed H{sub 2}. Quantum effects broaden the histograms with respect to their classical analogues and increase the expectation values of the radial and angular polar coordinates describing the location of the center-of-mass of the H{sub 2} molecule. The rigid-body PIMC simulations also provide estimates of the change in internal energy, ΔU{sub ads}, and enthalpy, ΔH{sub ads}, for H{sub 2} adsorption onto Li{sup +}-benzene, as a function of temperature. These estimates indicate that quantum effects are important even at room temperature and classical results should be interpreted with caution. Our results also show that anharmonicity is more important in the calculation of U and H than coupling—coupling between the intermolecular degrees of freedom becomes less important as temperature increases whereas anharmonicity becomes more important. The most anharmonic motions in H{sub 2}–Li{sup +}-benzene are the “helicopter” and “ferris wheel” H{sub 2} rotations. Treating these motions as one-dimensional free and hindered rotors, respectively, provides simple corrections to standard harmonic oscillator, rigid rotor thermochemical expressions for internal energy and enthalpy that encapsulate the majority of the anharmonicity. At 150 K, our best rigid-body PIMC estimates for ΔU{sub ads} and ΔH{sub ads} are −13.3 ± 0.1 and −14.5 ± 0.1 kJ mol{sup −1}, respectively.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Explaining the extra crystal-field mode in 𝐴 ⁢Ce ⁢𝑋 2 (𝐴 = K, Rb, Na; 𝑋 = O, S, Se, Te)

A growing list of Ce-based magnets have shown an extra and heretofore unexplained crystal electric field (CEF) mode at high energies. We describe a process whereby an optical phonon can produce a split CEF mode well above the phonon energy. We use density functional theory and point-charge model calculations to estimate the phonon distortions and coupling to model this effect in KCeO 2 , showing that it accounts for the extra CEF mode observed. Furthermore, this mechanism is generic and may explain the extra modes observed on a variety of Ce 3+ compounds.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Complete collision data set for electrons scattering on molecular hydrogen and its isotopologues: III. Vibrational excitation via electronic excitation and radiative decay

We present state-resolved cross sections for vibrational excitation via electronic excitation followed by radiative decay (ERD), for electrons scattering on all bound vibrational levels of the ground electronic state ($X\hspace{1.5 mm} ^1Σ_g^+$) of molecular hydrogen and its isotopologues (H 2 , HD, HT, D 2 , DT and T 2 ). We consider excitation of the singlet $\textit{n}$ = 2–3 states (where n refers to the united-atoms-limit principle quantum number) and account for all possible decay pathways back to the bound vibrational levels of the ground electronic state ($X\hspace{1.5 mm} ^1Σ_g^+$) to produce an estimate for the ERD cross sections. A selection of the results are presented in graphical form and a full data set is provided as both numerical values and analytic fit functions in supplementary data files. The uncertainty in the cross sections is estimated to be 11%, except for scattering on the highest bound vibrational level of HD, HT, D 2 , and DT, where the uncertainty is 21%. The data can be downloaded from the MCCC database at mccc-db.org.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2016

Methodology for Estimating Thermal and Neutron Embrittlement of Cast Austenitic Stainless Steels During Service in Light Water Reactors

Cast austenitic stainless steel (CASS) materials, which have a duplex structure consisting of austenite and ferrite phases, are susceptible to thermal embrittlement during reactor service. In addition, the prolonged exposure of these materials, which are used in reactor core internals, to neutron irradiation changes their microstructure and microchemistry, and these changes degrade their fracture properties even further. This paper presents a revision of the procedure and correlations presented in NUREG/CR-4513, Rev. 1 (Aug. 1994) for predicting the change in fracture toughness and tensile properties of CASS components due to thermal aging during service in light water reactors (LWRs) at 280–330 °C (535–625 °F). The methodology is applicable to CF-3, CF-3M, CF-8, and CF-8M materials with a ferrite content of up to 40%. The fracture toughness, tensile strength, and Charpy-impact energy of aged CASS materials are estimated from known material information. Embrittlement is characterized in terms of room-temperature (RT) Charpy-impact energy. The extent or degree of thermal embrittlement at “saturation” (i.e., the minimum impact energy that can be achieved for a material after long-term aging) is determined from the chemical composition of the material. Charpy-impact energy as a function of the time and temperature of reactor service is estimated from the kinetics of thermal embrittlement, which are also determined from the chemical composition. The fracture toughness J-R curve for the aged material is then obtained by correlating RT Charpy-impact energy with fracture toughness parameters. A common “predicted lower-bound” J-R curve for CASS materials of unknown chemical composition is also defined for a given grade of material, range of ferrite content, and temperature. In addition, guidance is provided for evaluating the combined effects of thermal and neutron embrittlement of CASS materials used in the reactor core internal components. The correlations for estimating the change in tensile strength, including the Ramberg/Osgood parameters for strain hardening, are also described.

Chopra, O. K.↗
DOE OSTI2018

Nonparametric Method of Least Squares: Accounting for Seasonality

We consider the problem of restoring a nonparametric dependence described by the sum of linear trend and seasonal component, i.e., a periodic function with the known period. We obtain the asymptotic distribution of the parameter estimates and the trend component. We find the mathematical expectation of the residual sum of squares. We also develop the methods of estimation of the seasonal component and construction of the interval forecast.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

X-Ray Bolometric Corrections for Compton-thick Active Galactic Nuclei

We present X-ray bolometric correction factors, κ{sub Bol} (≡L{sub Bol}/L{sub X}), for Compton-thick (CT) active galactic nuclei (AGNs) with the aim of testing AGN torus models, probing orientation effects, and estimating the bolometric output of the most obscured AGNs. We adopt bolometric luminosities, L{sub Bol}, from literature infrared (IR) torus modeling and compile published intrinsic 2–10 keV X-ray luminosities, L{sub X}, from X-ray torus modeling of NuSTAR data. Our sample consists of 10 local CT AGNs, where both of these estimates are available. We test for systematic differences in κ{sub Bol} values produced when using two widely used IR torus models and two widely used X-ray torus models, finding consistency within the uncertainties. We find that the mean κ{sub Bol} of our sample in the range of L{sub Bol}≈10{sup 42}--10{sup 45} erg s{sup −1} is log{sub 10} κ{sub Bol} = 1.44 ± 0.12 with an intrinsic scatter of ∼0.2 dex, and that our derived κ{sub Bol} values are consistent with previously established relationships between κ{sub Bol} and L{sub Bol} and κ{sub Bol} and Eddington ratio (λ{sub Edd}). We investigate if κ{sub Bol} is dependent on N{sub H} by comparing our results on CT AGNs to published results on less-obscured AGNs, finding no significant dependence. Since many of our sample are megamaser AGNs, known to be viewed edge-on, and furthermore under the assumptions of AGN unification whereby unobscured AGNs are viewed face-on, our result implies that the X-ray emitting corona is not strongly anisotropic. Finally, we present κ{sub Bol} values for CT AGNs identified in X-ray surveys as a function of their observed L{sub X}, where an estimate of their intrinsic L{sub X} is not available, and redshift, useful for estimating the bolometric output of the most obscured AGNs across cosmic time.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2016

Action-based dynamical modeling for the Milky Way disk

We present RoadMapping, a full-likelihood dynamical modeling machinery that aims to recover the Milky Way’s (MW) gravitational potential from large samples of stars in the Galactic disk. RoadMapping models the observed positions and velocities of stars with a parameterized, three-integral distribution function (DF) in a parameterized axisymmetric potential. We investigate through differential test cases with idealized mock data how the breakdown of model assumptions and data properties affect constraints on the potential and DF. Our key results are: (i) If the MW’s true potential is not included in the assumed model potential family, we can—in the axisymmetric case—still find a robust estimate for the potential, with only ≲10% difference in surface density within |z|⩽1.1 kpc inside the observed volume. (ii) Modest systematic differences between the true and model DF are inconsequential. E.g., when binning stars to define sub-populations with simple DFs, binning errors do not affect the modeling as long as the DF parameters of neighboring bins differ by <20%. In addition, RoadMapping ensures unbiased potential estimates for either (iii) small misjudgements of the spatial selection function (i.e., ≲15% at the survey volume’s edge), (iv) if distances are known to within 10%, or (v) if proper motion uncertainties are known within 10% or are smaller than δμ≲1 mas yr{sup −1}. Challenges are the rapidly increasing computational costs for large sample sizes. Overall, RoadMapping is well suited to making precise new measurements of the MW’s potential with data from the upcoming Gaia releases.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

ReLU, Sparseness, and the Encoding of Optic Flow in Neural Networks

Accurate self-motion estimation is critical for various navigational tasks in mobile robotics. Optic flow provides a means to estimate self-motion using a camera sensor and is particularly valuable in GPS- and radio-denied environments. The present study investigates the influence of different activation functions—ReLU, leaky ReLU, GELU, and Mish—on the accuracy, robustness, and encoding properties of convolutional neural networks (CNNs) and multi-layer perceptrons (MLPs) trained to estimate self-motion from optic flow. Our results demonstrate that networks with ReLU and leaky ReLU activation functions not only achieved superior accuracy in self-motion estimation from novel optic flow patterns but also exhibited greater robustness under challenging conditions. The advantages offered by ReLU and leaky ReLU may stem from their ability to induce sparser representations than GELU and Mish do. Our work characterizes the encoding of optic flow in neural networks and highlights how the sparseness induced by ReLU may enhance robust and accurate self-motion estimation from optic flow.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2013

RETIRED A STARS: THE EFFECT OF STELLAR EVOLUTION ON THE MASS ESTIMATES OF SUBGIANTS

Doppler surveys have shown that the occurrence rate of Jupiter-mass planets appears to increase as a function of stellar mass. However, this result depends on the ability to accurately measure the masses of evolved stars. Recently, Lloyd called into question the masses of subgiant stars targeted by Doppler surveys. Lloyd argues that very few observable subgiants have masses greater than 1.5 M {sub Sun }, and that most of them have masses in the range 1.0-1.2 M {sub Sun }. To investigate this claim, we use Galactic stellar population models to generate an all-sky distribution of stars. We incorporate the effects that make massive subgiants less numerous, such as the initial mass function and differences in stellar evolution timescales. We find that these effects lead to negligibly small systematic errors in stellar mass estimates, in contrast to the Almost-Equal-To 50% errors predicted by Lloyd. Additionally, our simulated target sample does in fact include a significant fraction of stars with masses greater than 1.5 M {sub Sun }, primarily because the inclusion of an apparent magnitude limit results in a Malmquist-like bias toward more massive stars, in contrast to the volume-limited simulations of Lloyd. The magnitude limit shifts the mean of our simulated distribution toward higher masses and results in a relatively smaller number of evolved stars with masses in the range 1.0-1.2 M {sub Sun }. We conclude that, within the context of our present-day understanding of stellar structure and evolution, many of the subgiants observed in Doppler surveys are indeed as massive as main-sequence A stars.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2014

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Improving Convection Trigger Functions in Deep Convective Parameterization Schemes Using Machine Learning

Abstract Deficiencies in convection trigger functions, used in deep convection parameterizations in General Circulation Models (GCMs), have critical impacts on climate simulations. A novel convection trigger function is developed using the machine learning (ML) classification model XGBoost. The large‐scale environmental information associated with convective events is obtained from the long‐term constrained variational analysis forcing data from the Atmospheric Radiation Measurement (ARM) program at its Southern Great Plains (SGP) and Manaus (MAO) sites representing, respectively, continental mid‐latitude and tropical convection. The ML trigger is separately trained and evaluated per site, and jointly trained and evaluated at both sites as a unified trigger. The performance of the ML trigger is compared with four convective trigger functions commonly used in GCMs: dilute convective available potential energy (CAPE), undilute CAPE, dilute dynamic CAPE (dCAPE), and undilute dCAPE. The ML trigger substantially outperforms the four CAPE‐based triggers in terms of the F 1 score metric, widely used to estimate the performance of ML methods. The site‐specific ML trigger functions can achieve, respectively, 91% and 93% F 1 scores at SGP and MAO. The unified trigger also has a 91% F 1 score, with virtually no degradation from the site‐specific training, suggesting the potential of a global ML trigger function. The ML trigger alleviates a GCM deficiency regarding the overprediction of convection occurrence, offering a promising improvement to the simulation of the diurnal cycle of precipitation. Furthermore, to overcome the black box issue of the ML methods, insights derived from the ML model are discussed, which may be leveraged to improve traditional CAPE‐based triggers.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

MODERATE C IV ABSORBER SYSTEMS REQUIRE 10{sup 12} M{sub Sun} DARK MATTER HALOS AT z {approx} 2.3: A CROSS-CORRELATION STUDY OF C IV ABSORBER SYSTEMS AND QUASARS IN SDSS-III BOSS DR9

We measure the two-point cross-correlation function of C IV absorber systems and quasars, using spectroscopic data from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey (BOSS; Data Release 9). The 19,701 quasars and 6149 C IV ''moderate'' absorbers, 0.28 A < rest-frame equivalent width (EW) < 5 A, in our study cover a redshift range of 2.1 < z < 2.5 over 3300 deg{sup 2} and represent a factor of two increase in sample size over previous investigations. We find a correlation scale length and slope of the redshift-space cross-correlation function of s{sub 0} = 8.46 {+-} 1.24 Mpc, {gamma} = 1.68 {+-} 0.19, in the redshift-space range 10 < s < 100 Mpc. We find a projected cross-correlation function of C IV absorption systems and quasars of r{sub 0} = 7.76 {+-} 2.80 Mpc, {gamma} = 1.74 {+-} 0.21. We measure the combined quasar and C IV bias to be b{sub QSO} b{sub C{sub IV}} = 8.81 {+-} 2.28. Using an estimate of b{sub QSO} from the quasar auto-correlation function we find b{sub CIV} = 2.38 {+-} 0.62. This b{sub CIV} implies that EW > 0.28 A C IV absorbers at z {approx} 2.3 are typically found in dark matter halos that have masses {>=}10{sup 11.3}-10{sup 13.4} M{sub Sun} at that redshift. The complete BOSS sample will triple the number of both quasars and absorption systems and increase the power of this cross-correlation measurement by a factor of two.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

Constraining radio mode feedback in galaxy clusters with the cluster radio AGNs properties to z ∼ 1

ABSTRACT We study the properties of the Sydney University Molonglo Sky Survey (SUMSS) 843 MHz radio active galactic nuclei (AGNs) population in galaxy clusters from two large catalogues created using the Dark Energy Survey (DES): ∼11 800 optically selected RM-Y3 and ∼1000 X-ray selected MARD-Y3 clusters. We show that cluster radio loud AGNs are highly concentrated around cluster centres to $z$ ∼ 1. We measure the halo occupation number for cluster radio AGNs above a threshold luminosity, finding that the number of radio AGNs per cluster increases with cluster halo mass as N ∝ M1.2 ± 0.1 (N ∝ M0.68 ± 0.34) for the RM-Y3 (MARD-Y3) sample. Together, these results indicate that radio mode feedback is favoured in more massive galaxy clusters. Using optical counterparts for these sources, we demonstrate weak redshift evolution in the host broad-band colours and the radio luminosity at fixed host galaxy stellar mass. We use the redshift evolution in radio luminosity to break the degeneracy between density and luminosity evolution scenarios in the redshift trend of the radio AGNs luminosity function (LF). The LF exhibits a redshift trend of the form (1 + $z$)γ in density and luminosity, respectively, of γD = 3.0 ± 0.4 and γP = 0.21 ± 0.15 in the RM-Y3 sample, and γD = 2.6 ± 0.7 and γP = 0.31 ± 0.15 in MARD-Y3. We discuss the physical drivers of radio mode feedback in cluster AGNs, and we use the cluster radio galaxy LF to estimate the average radio-mode feedback energy as a function of cluster mass and redshift and compare it to the core (<0.1R500) X-ray radiative losses for clusters at $z$ < 1.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Sub-barrier fusion of weakly bound Li 6 with Ni 58

Evaporation-proton yields were measured for the fusion of the weakly bound nucleus 6 Li on a 58 Ni target at six near- or sub-barrier bombarding energies. Effects of the one-neutron transfer reaction were estimated and corrections made. Total-fusion cross sections were deduced using calculated proton multiplicities. The resulting fusion excitation function shows a considerable enhancement with respect to calculations for a bare potential. Inelastic couplings are estimated to have insignificant effects on such fusion. Here, the sum of total fusion plus one-neutron transfer cross sections nearly saturates the total reaction cross section in the energy region measured. Comparison with previous results appropriately scaled for the 6 Li+( 59 Co, 64 Ni, 64 Zn) systems shows good consistency except for some data spread at the lower energies.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2013

Ancient light from young cosmic cities: Physical and observational signatures of galaxy proto-clusters

A growing number of galaxy clusters at z = 1-2 is being discovered as part of deep optical, IR, X-ray, and Sunyaev-Zel'dovich effect surveys. For a complete picture of cluster formation, however, it is important that we also start probing the much earlier epoch, between redshifts of about 2 and 7, during which these clusters and their galaxies first began to form. Because the study of these so-called proto-clusters is currently quite limited by small number statistics, widely varying selection techniques, and many assumptions, we have performed a large systematic study of cluster formation utilizing cosmological simulations. We use the Millennium Simulations to track the evolution of dark matter and galaxies in about 3000 clusters from the earliest times to z = 0. We define an effective radius R{sub e} for proto-clusters and characterize their growth in size and mass with cosmic time. We show that the progenitor regions of galaxy clusters (ranging in mass from ∼10{sup 14} to a few times 10{sup 15} M {sub ☉}) can already be identified in galaxy surveys at very early times (at least up to z ∼ 5), provided that the galaxy overdensities are measured on a sufficiently large scale (R{sub e} ∼ 5-10 Mpc comoving) and with sufficient statistics. We present the overdensities in matter, dark matter halos, and galaxies as functions of present-day cluster mass, redshift, bias, and window size that can be used to interpret the wide range of structures found in real surveys. We also derive the probability that a structure having a galaxy overdensity δ{sub gal}, defined by a set of observational selection criteria, is indeed a proto-cluster, and we show how their z = 0 masses can already be estimated long before virialization. We present overdensity profiles as a function of radius, and we further show how the projected surface overdensities of proto-clusters decrease as the uncertainties in redshift measurements increase. We provide a table of proto-cluster candidates selected from the literature and discuss their properties in light of our simulation predictions. This paper provides the general framework that will allow us to extend the study of cluster formation out to much higher redshifts using the large number of proto-clusters that are expected to be discovered in, e.g., the upcoming HETDEX and Hyper Suprime-Cam surveys.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2019

A Novel Statistical Method for Measuring the Temperature–Density Relation in the IGM Using the b – N Hi Distribution of Absorbers in the Ly α Forest

We propose a new method for determining the thermal state of the intergalactic medium based on Voigt profile decomposition of the Lyα forest. The distribution of Doppler parameter and column density (b–N H i distribution) is sensitive to the temperature–density relation T = T 0 (ρ/ρ 0 ) γ-1 , and previous work has inferred T 0 and γ by fitting its low-b cutoff. This approach discards the majority of available data and is susceptible to systematics related to cutoff determination. We introduce an approach that exploits all information encoded in the b – N H i distribution by modeling its entire shape. We apply kernel density estimation to discrete absorption lines to generate model probability density functions, and then we use principal component decomposition to create an emulator that can be evaluated anywhere in thermal parameter space. We introduce a Bayesian likelihood based on these models enabling parameter inference via Markov Chain Monte Carlo. The method's robustness is tested by applying it to a large grid of thermal history simulations. By conducting 160 mock measurements, we establish that our approach delivers unbiased estimates and valid uncertainties for a 2D ( T 0 , γ) measurement. Furthermore, we conduct a pilot study applying this methodology to real observational data at z = 2. Using 200 absorbers, equivalent in path length to a single Lya forest spectrum, we measure $\mathrm{log}{T}_{0}={4.092}_{-0.055}^{+0.050}$ and $\gamma ={1.49}_{-0.074}^{+0.073}$ in excellent agreement with cutoff fitting determinations using the same data. Our method is far more sensitive than cutoff fitting, enabling measurements of log T 0 and γ with precision on $\mathrm{log}{T}_{0}$ (γ) nearly two (three) times higher for current data set sizes.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Time to Amyloid Positivity and Preclinical Changes in Brain Metabolism, Atrophy, and Cognition: Evidence for Emerging Amyloid Pathology in Alzheimer's Disease

Background: Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition. Methods: In 89 cognitively healthy elders with up to 10 years of follow-up, we estimated the points at which rates of fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to the time to Aβ-positivity. Points of initial acceleration in rates of decline were estimated using mixed-effects models with penalized regression splines. Results: Acceleration of rates of FDG PET were observed to occur 20+ years before the conventional threshold for Aβ-positivity. Subtle signs of cognitive dysfunction were observed 10+ years before Aβ-positivity. Conclusions: Aβ may have subtle associations with other hallmarks of Alzheimer’s disease before Aβ biomarkers reach conventional thresholds for Aβ-positivity. Therefore, we propose that emerging Aβ pathology occurs many years before cognitively healthy elders reach the current threshold for Aβ positivity (preclinical AD). To allow prevention in the earliest disease stages, AD clinical trials may be designed to also include subjects with Aβ biomarkers in the sub-threshold range.

59 BASIC BIOLOGICAL SCIENCES↗