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All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Evaluation of partial volume correction and analysis of longitudinal [ 18 F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [ 18 F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM). Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates. Results: The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability. Conclusion: The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [ 18 F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability. Clinical trial registration: NCT02640092 and NCT03289143.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation

The early stages of Alzheimer’s disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future pathological tau accumulation. In particular, we use machine learning to quantify interactions between key pathological markers (β-amyloid, medial temporal lobe atrophy, tau and APOE 4) at mildly impaired and asymptomatic stages of AD. Using baseline non-tau markers we derive a prognostic index that: (a) stratifies patients based on future pathological tau accumulation, (b) predicts individualised regional future rate of tau accumulation, and (c) translates predictions from deep phenotyping patient cohorts to cognitively normal individuals. Our results propose a robust approach for fine scale stratification and prognostication with translation impact for clinical trial design targeting the earliest stages of AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (–0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p’s > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R 2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease

Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer’s disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET onN = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5; range, 1.2 to 8.1) period for Aβ and tau, respectively, ~14 years after the initiation of HT. In older women (aged >70 years), HT users exhibited faster regional tau accumulation relative to non-users, localized to the entorhinal cortex and the inferior temporal and fusiform gyri, with an indirect effect of HT on cognitive decline through regional tau accumulation. In younger women (aged <70 years), HT associations with tau accumulation were negligible. Findings are relevant for optimizing menopausal treatment guidelines.

Science & Technology - Other Topics↗
DOE OSTI2022

Detection of astrophysical tau neutrino candidates in IceCube

High-energy tau neutrinos are rarely produced in atmospheric cosmic-ray showers or at cosmic particle accelerators, but are expected to emerge during neutrino propagation over cosmic distances due to flavor mixing. When high energy tau neutrinos interact inside the IceCube detector, two spatially separated energy depositions may be resolved, the first from the charged current interaction and the second from the tau lepton decay. We report a novel analysis of 7.5 years of IceCube data that identifies two candidate tau neutrinos among the 60 “High-Energy Starting Events” (HESE) collected during that period. The HESE sample offers high purity, all-sky sensitivity, and distinct observational signatures for each neutrino flavor, enabling a new measurement of the flavor composition. The measured astrophysical neutrino flavor composition is consistent with expectations, and an astrophysical tau neutrino flux is indicated at 2.8σ significance.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Evaluation of a visual interpretation method for tau-PET with 18 F-flortaucipir

Introduction: Positron emission tomography targeting tau (tau-PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed. Methods: In this work, we developed a visual interpretation method for 18 F-flortaucipir tau-PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non-AD diagnoses). Two readers interpreted 18 F-flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern. Results: Global visual scores were reliable, correlated with global cortical 18 F-flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD-like 18 F-flortaucipir pattern had good sensitivity and specificity to identify amyloid-positive patients with AD dementia or MCI. Discussion: This 18 F-flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Locus coeruleus catecholamines link neuroticism and vulnerability to tau pathology in aging

Higher neuroticism is a risk factor for Alzheimer's disease (AD), and is implicated in disordered stress responses. The locus coeruleus (LC)-catecholamine system is activated during perceived threat and is a centerpiece of developing models of the pathophysiology of AD, as it is the first brain region to develop abnormal tau. We examined relationships among the "Big 5" personality traits, LC catecholamine synthesis capacity measured with [ 18 F]Fluoro-m-tyrosine PET, and tau burden measured with [ 18 F]Flortaucipir PET in cognitively normal older adults (n = 47). β-amyloid (Aβ) status was determined using [ 11 C]Pittsburgh compound B PET (n = 14 Aβ positive). Lower LC catecholamine synthesis capacity was associated with higher neuroticism, more depressive symptoms as measured by the Geriatric Depression Scale, and higher amygdala tau-PET binding. Exploratory analyses with other personality traits revealed that low trait conscientiousness was also related to both lower LC catecholamine synthesis capacity, and more depressive symptoms. A significant indirect path linked both high neuroticism and low conscientiousness to greater amygdala tau burden via their mutual association with low LC catecholamine synthesis capacity. Together, these findings reveal LC catecholamine synthesis capacity to be a promising marker of affective health and pathology burden in aging, and identifies candidate neurobiological mechanisms for the effect of personality on increased vulnerability to dementia.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Tau tridents at accelerator neutrino facilities

We present the first detailed study of Standard Model neutrino tridents involving tau leptons at the near detectors of accelerator neutrino facilities. The rates of these processes were previously thought to be negligible, even at future facilities. Our full 2 → 4 calculation, including both coherent and incoherent scatterings, reveals that the DUNE near detector could observe a considerable number of tau tridents—an important background to new physics searches. We identify promising kinematic features that may allow distinction of tau tridents from the usual neutrino charged-current background at DUNE, and thus establish the observation of tau tridents for the first time. We also comment on the detection prospects at other accelerator and collider neutrino experiments.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2022

The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of [ 18 F]MK6240 Tau PET in Target Regions

6-(fluoro- 18 F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([ 18 F]MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention on the longitudinal quantification of [ 18 F]MK6240 in target regions. Methods: We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzheimer disease spectrum with longitudinal [ 18 F]MK6240 SUVs and SUV ratios (SUVRs) (mean ± SD, 2.25 ± 0.40 y of follow-up). We obtained SUVR from meninges, exhibiting frequent off-target retention with [ 18 F]MK6240. Additionally, we compared tracer uptake between 37 cognitively unimpaired young (CUY) (mean age, 23.41 ± 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-β–negative and tau-negative, 58.50 ± 9.01 y) to identify possible nonvisually apparent, age-related signal. Two-tailed t testing and Pearson correlation testing were used to determine the difference between groups and associations between changes in region uptake, respectively. Results: Inferior cerebellar gray matter SUV did not differ on the basis of diagnosis and amyloid-β status, cross-sectionally and over time. [ 18 F]MK6240 uptake significantly differed between CUY and CU adults in the putamen or pallidum (affecting ~75% of the region) and in the Braak II region (affecting ~35%). Changes in meningeal and putamen or pallidum SUVRs did not significantly differ from zero, nor did they vary across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were strongly correlated. Conclusion: Inferior cerebellar gray matter was similar across diagnostic groups cross-sectionally and stable over time and thus was deemed a suitable reference region for quantification. Despite not being visually perceptible, [ 18 F]MK6240 has age-related retention in subcortical regions, at a much lower magnitude but topographically colocalized with significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related or meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. Nevertheless, the age-related retention in the Braak II region needs to be further investigated. Future postmortem studies should elucidate the source of the newly reported age-related [ 18 F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Distinct effects of beta-amyloid and tau on cortical thickness in cognitively healthy older adults

Published reports of associations between β-amyloid (Aβ) and cortical integrity conflict. Tau biomarkers may help elucidate the complex relationship between pathology and neurodegeneration in aging. We measured cortical thickness using magnetic resonance imaging, Aβ using Pittsburgh compound B positron emission tomography (PiB-PET), and tau using flortaucipir (FTP)-PET in 125 cognitively normal older adults. We examined relationships among PET measures, cortical thickness, and cognition. Cortical thickness was reduced in PiB+/FTP+ participants compared to the PiB+/FTP– and PiB–/FTP– groups. Continuous PiB associations with cortical thickness were weak but positive in FTP– participants and negative in FTP+. FTP strongly negatively predicted thickness regardless of PiB status. FTP was associated with memory and cortical thickness, and mediated the association of PiB with memory. Past findings linking Aβ and cortical thickness are likely weak due to opposing effects of Aβ on cortical thickness relative to tau burden. Tau, in contrast to Aβ, is strongly related to cortical thickness and memory.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Measurement of the Higgs boson production rate in association with top quarks in final states with electrons, muons, and hadronically decaying tau leptons at $\sqrt{s} =$ 13 TeV

The rate for Higgs (${\mathrm{H}} $) bosons production in association with either one (${\mathrm{t}} {\mathrm{H}} $) or two (${\mathrm{t}} {{\overline{{{\mathrm{t}}}}}} {\mathrm{H}} $) top quarks is measured in final states containing multiple electrons, muons, or tau leptons decaying to hadrons and a neutrino, using proton–proton collisions recorded at a center-of-mass energy of $13\,\text {Te}\text {V} $ by the CMS experiment. The analyzed data correspond to an integrated luminosity of 137$\,\text {fb}^{-1}$. The analysis is aimed at events that contain ${\mathrm{H}} \rightarrow {\mathrm{W}} {\mathrm{W}} $, ${\mathrm{H}} \rightarrow {\tau } {\tau } $, or ${\mathrm{H}} \rightarrow {\mathrm{Z}} {\mathrm{Z}} $ decays and each of the top quark(s) decays either to lepton+jets or all-jet channels. Sensitivity to signal is maximized by including ten signatures in the analysis, depending on the lepton multiplicity. The separation among ${\mathrm{t}} {\mathrm{H}} $, ${\mathrm{t}} {{\overline{{{\mathrm{t}}}}}} {\mathrm{H}} $, and the backgrounds is enhanced through machine-learning techniques and matrix-element methods. The measured production rates for the ${\mathrm{t}} {{\overline{{{\mathrm{t}}}}}} {\mathrm{H}} $ and ${\mathrm{t}} {\mathrm{H}} $ signals correspond to $0.92 \pm 0.19\,\text {(stat)} ^{+0.17}_{-0.13}\,\text {(syst)} $ and $5.7 \pm 2.7\,\text {(stat)} \pm 3.0\,\text {(syst)} $ of their respective standard model (SM) expectations. The corresponding observed (expected) significance amounts to 4.7 (5.2) standard deviations for ${\mathrm{t}} {{\overline{{{\mathrm{t}}}}}} {\mathrm{H}} $, and to 1.4 (0.3) for ${\mathrm{t}} {\mathrm{H}} $ production. Assuming that the Higgs boson coupling to the tau lepton is equal in strength to its expectation in the SM, the coupling $y_{{\mathrm{t}}}$ of the Higgs boson to the top quark divided by its SM expectation, $\kappa _{{\mathrm{t}}}=y_{{\mathrm{t}}}/y_{{\mathrm{t}}}^{\mathrm {SM}}$, is constrained to be within $-0.9< \kappa _{{\mathrm{t}}}< -0.7$ or $0.7< \kappa _{{\mathrm{t}}}< 1.1$, at 95% confidence level. This result is the most sensitive measurement of the ${\mathrm{t}} {{\overline{{{\mathrm{t}}}}}} {\mathrm{H}} $ production rate to date.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

An Asymmetric Eclipse Seen toward the Pre-main-sequence Binary System V928 Tau

K2 observations of the weak-lined T Tauri binary V928 Tau A and B show the detection of a single, asymmetric eclipse, which may be due to a previously unknown substellar companion eclipsing one component of the binary with an orbital period >66 days. Over an interval of about 9 hr, one component of the binary dims by around 60%, returning to its normal brightness about 5 hr later. From modeling of the eclipse shape, we find evidence that the eclipsing companion may be surrounded by a disk or a vast ring system. The modeled disk has a radius of 0.9923 ± 0.0005 R&lowast;, with an inclination of 56.°78 ± 0.°03, a tilt of 41.°22 ± 0.°05, an impact parameter of -0.2506 ± 0.0002 R&lowast;, and an opacity of 1.00. The occulting disk must also move at a transverse velocity of 6.637 ± 0.002 R&lowast; day -1 , which, depending on whether it orbits V928 Tau A or B, corresponds to approximately 73.53 or 69.26 km s -1 . A search in ground-based archival data reveals additional dimming events, some of which suggest periodicity, but no unambiguous period associated with the eclipse observed by K2. We present a new epoch of astrometry that is used to further refine the orbit of the binary, presenting a new lower bound of 67 yr, and constraints on the possible orbital periods of the eclipsing companion. The binary is also separated by 18' (~2250 au) from the lower-mass CFHT-BD-Tau 7, which is likely associated with V928 Tau A and B. We also present new high-dispersion optical spectroscopy that we use to characterize the unresolved stellar binary.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

An Asymmetric Dust Ring around a Very Low Mass Star ZZ Tau IRS

We present Atacama Large Millimeter/submillimeter Array (ALMA) gas and dust observations at band 7 (339 GHz: 0.89 mm) of the protoplanetary disk around a very low mass star ZZ Tau IRS with a spatial resolution of 025. The {sup 12}CO J = 3 → 2 position–velocity diagram suggests a dynamical mass of ZZ Tau IRS of ∼0.1–0.3 M {sub ☉}. The disk has a total flux density of 273.9 mJy, corresponding to an estimated mass of 24–50 M {sub ⊕} in dust. The dust emission map shows a ring at r = 58 au and an azimuthal asymmetry at r = 45 au with a position angle of 135°. The properties of the asymmetry, including radial width, aspect ratio, contrast, and contribution to the total flux, were found to be similar to the asymmetries around intermediate mass stars (∼2 M {sub ☉}) such as MWC 758 and IRS 48. This implies that the asymmetry in the ZZ Tau IRS disk shares a similar origin with others, despite the star being ∼10 times less massive. Our observations also suggest that the inner and outer parts of the disk may be misaligned. Overall, the ZZ Tau IRS disk shows evidence of giant planet formation on a ∼10 au scale at a few megayears. If confirmed, it will challenge existing core accretion models in which such planets have been predicted to be extremely hard to form around very low mass stars.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2023

Successful cognitive aging is associated with thicker anterior cingulate cortex and lower tau deposition compared to typical aging

INTRODUCTION There is no consensus on either the definition of successful cognitive aging (SA) or the underlying neural mechanisms. METHODS We examined the agreement between new and existing definitions using: (1) a novel measure, the cognitive age gap (SA-CAG, cognitive-predicted age minus chronological age), (2) composite scores for episodic memory (SA-EM), (3) non-memory cognition (SA-NM), and (4) the California Verbal Learning Test (SA-CVLT). RESULTS Fair to moderate strength of agreement was found between the four definitions. Most SA groups showed greater cortical thickness compared to typical aging (TA), especially in the anterior cingulate and midcingulate cortices and medial temporal lobes. Greater hippocampal volume was found in all SA groups except SA-NM. Lower entorhinal 18 F-Flortaucipir (FTP) uptake was found in all SA groups. DISCUSSION These findings suggest that a feature of SA, regardless of its exact definition, is resistance to tau pathology and preserved cortical integrity, especially in the anterior cingulate and midcingulate cortices. Highlights: Different approaches have been used to define successful cognitive aging (SA). Regardless of definition, different SA groups have similar brain features. SA individuals have greater anterior cingulate thickness and hippocampal volume. Lower entorhinal tau deposition, but not amyloid beta is related to SA. A combination of cortical integrity and resistance to tau may be features of SA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Tau accumulation and atrophy predict amyloid independent cognitive decline in aging

INTRODUCTION: Amyloid beta (Aβ) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD). METHODS: We investigated relationships between concurrent longitudinal measures of Aβ (Pittsburgh compound B [PiB] positron emission tomography [PET]), tau (flortaucipir [FTP] PET), atrophy (structural magnetic resonance imaging), episodic memory (EM), and non-memory (NM) in 78 cognitively healthy older adults (OA). RESULTS: Entorhinal FTP change was correlated with EM decline regardless of Aβ, but meta-temporal FTP and global PiB change were only associated with EM and NM decline in Aβ+ OA. Voxel-wise analyses revealed significant associations between temporal lobe FTP change and EM decline in all groups. PiB and FTP change were not associated with structural change, suggesting a functional or microstructural mechanism linking these measures to cognitive decline. DISCUSSION: Our results show that longitudinal Aβ is linked to cognitive decline only in the presence of elevated Aβ, but longitudinal temporal lobe tau is associated with memory decline regardless of Aβ status.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Search for the pair production of long-lived supersymmetric partners of the tau lepton in proton-proton collisions at $\sqrt{s}=13$ TeV

Gauge-mediated supersymmetry-breaking models provide a strong motivation to search for a supersymmetric partner of the tau lepton (stau) with a macroscopic lifetime. Long-lived stau decays produce tau leptons that are displaced from the primary proton-proton interaction vertex, leading to an unconventional signature. This paper presents a search for the direct production of long-lived staus decaying within the CMS tracker volume in proton-proton collisions at $\sqrt{s}=13$ TeV, performed for the first time with an identification algorithm based on a graph neural network dedicated to displaced tau leptons. The data sample, corresponding to an integrated luminosity of 138 fb −1 , was recorded with the CMS experiment at the CERN LHC between 2016 and 2018. This search excludes, at 95% confidence level, stau masses, m~ τ , in the 126–260 (90–425) GeV range for a proper decay length of 50 mm in the maximally mixed (mass-degenerate) scenario, while for m~ τ = 200 GeV, stau proper decay lengths are excluded in the range 21–94 (6–333) mm. These results improve the exclusion limits compared to previous searches, and extend the parameter space explored in the context of supersymmetry.

Hadron-Hadron Scattering↗
DOE OSTI2025

Search for lepton-flavor-violating ${\tau }^{-}\to {{\ell}}^{-}{K}_{s}^{0}$ decays at Belle and Belle II

We present the results of a search for charged-lepton-flavor violating decays ${\tau }^{-}\to {{\ell}}^{-}{K}_{s}^{0}$, where ℓ − is either an electron or a muon. We combine e + e − data samples recorded by the Belle II experiment at the SuperKEKB collider (428 fb −1 ) with samples recorded by the Belle experiment at the KEKB collider (980 fb −1 ) to obtain a sample of 1.3 billion e + e − → τ + τ − events. We observe 0 and 1 events and set 90% confidence level upper limits of 0.8 × 10 −8 and 1.2 × 10 −8 on the branching fractions of the decay modes ${\tau }^{-}\to {e}^{-}{K}_{S}^{0}$ and ${\tau }^{-}\to {\mu }^{-}{K}_{S}^{0}$, respectively. These are the most stringent upper limits to date.

beyond Standard Model↗
DOE OSTI2023

Heterogeneous Graph Neural Network for identifying hadronically decayed tau leptons at the High Luminosity LHC

Here, we present a new algorithm that identifies reconstructed jets originating from hadronic decays of tau leptons against those from quarks or gluons. No tau lepton reconstruction algorithm is used. Instead, the algorithm represents jets as heterogeneous graphs with tracks and energy clusters as nodes and trains a Graph Neural Network to identify tau jets from other jets. Different attributed graph representations and different GNN architectures are explored. We propose to use differential track and energy cluster information as node features and a heterogeneous sequentially-biased encoding for the inputs to final graph-level classification.

47 OTHER INSTRUMENTATION↗