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At least 91 records · Page 5

Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease.

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

60 APPLIED LIFE SCIENCES↗

Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation

In neurodegenerative diseases including Alzheimer’s and amyotrophic lateral sclerosis, proteins that bind RNA are found in aggregated forms in autopsied brains. Evidence suggests that RNA aids nucleation of these pathological aggregates; however, the mechanism has not been investigated at the level of atomic structure. Here, we present the 3.4-Å resolution structure of fibrils of full-length recombinant tau protein in the presence of RNA, determined by electron cryomicroscopy (cryo-EM). The structure reveals the familiar in-register cross-β amyloid scaffold but with a small fibril core spanning residues Glu391 to Ala426, a region disordered in the fuzzy coat in all previously studied tau polymorphs. RNA is bound on the fibril surface to the positively charged residues Arg406 and His407 and runs parallel to the fibril axis. The fibrils dissolve when RNase is added, showing that RNA is necessary for fibril integrity. While this structure cannot exist simultaneously with the tau fibril structures extracted from patients’ brains, it could conceivably account for the nucleating effects of RNA cofactors followed by remodeling as fibrils mature.

59 BASIC BIOLOGICAL SCIENCES↗

High-level hadronic tau lepton triggers of the CMS experiment in proton-proton collisions at √(s) = 13.6 TeV

The trigger system of the CMS detector is pivotal in the acquisition of data for physics measurements and searches. Studies of final states characterized by hadronic decays of tau leptons require the reconstruction and the identification of genuine tau leptons against quark- and gluon-initiated jets at the trigger level. This is a difficult task, particularly as improvements to the LHC have resulted in an increased number of interactions per bunch crossing in recent years. To address this challenge, a series of machine-learning algorithms with high identification efficiency and low computational cost have been incorporated into the high-level trigger for hadronically decaying tau leptons. In this paper, these developments and the trigger performance are summarized using data collected by the CMS experiment in proton-proton collisions at √(s) = 13.6 TeV in 2022–2023, corresponding to an integrated luminosity of 62 fb -1 .

Particle identification methods↗

Measurement of $\tau _\text {L}$ using the ${B} _s^0 \rightarrow J/\psi \eta$ decay mode

Using a proton–proton collision data sample collected by the LHCb detector and corresponding to an integrated luminosity of $5.7~\text {fb}^{-1}$ , the lifetime of the light ${{B} ^0_{s}}$ mass eigenstate, $\tau _{L}$ , is measured using the $B^0_s \rightarrow J/\psi \eta$ decay mode to be $\begin{aligned} \tau _{\text {L}} = 1.445 \pm 0.016 \text {(stat)} \pm 0.008 \text {(syst)} \,\text {ps}. \end{aligned}$ A combination of this result with a previous LHCb analysis using an independent dataset corresponding to 3 fb –1 of integrated luminosity gives $\begin{aligned} \tau _{\text {L}} = 1.452 \pm 0.014 \pm 0.007 \pm 0.002 \,\text {ps}, \end{aligned}$ where the first uncertainty is statistical, the second due to the uncorrelated part of the systematic uncertainty and the third due to the correlated part of the systematic uncertainty.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Search for pair production of third-generation leptoquarks decaying into a bottom quark and a $\tau $-lepton with the ATLAS detector

Abstract A search for pair-produced scalar or vector leptoquarks decaying into a b -quark and a $$\tau $$ τ -lepton is presented using the full LHC Run 2 (2015–2018) data sample of 139 fb $$^{-1}$$ - 1 collected with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of $$\sqrt{s} =13$$ s = 13 TeV. Events in which at least one $$\tau $$ τ -lepton decays hadronically are considered, and multivariate discriminants are used to extract the signals. No significant deviations from the Standard Model expectation are observed and 95% confidence-level upper limits on the production cross-section are derived as a function of leptoquark mass and branching ratio $$\mathcal {B}$$ B into a $$\tau $$ τ -lepton and b -quark. For scalar leptoquarks, masses below 1460 GeV are excluded assuming $$\mathcal {B}=100$$ B = 100 %, while for vector leptoquarks the corresponding limit is 1650 GeV (1910 GeV) in the minimal-coupling (Yang–Mills) scenario.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology

Background: Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Methods: Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Results: Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with ADrelated traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant. Conclusions: Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD. Keywords: BIN1 isoforms, Alzheimer’s disease, Amyloid, Tau, Microglia, Astrocytes, Neurons

Taga, Mariko↗

3D-Reconstruction of Tau Neutrinos in LArTPC Detectors

The Deep Underground Neutrino Experiment (DUNE) is a next-generation neutrino experiment currently under construction. DUNE will consist of two high-resolution neutrino interaction imaging detectors exposed to the world’s most intense neutrino beam, with the Near Detector at Fermilab and the Far Detector 1,300 km away in the Sanford Underground Research Facility in South Dakota, US. The high statistics and excellent resolution capabilities of DUNE's $^{40}$Ar detector will allow us to make precision studies of oscillation parameters capable of searching for CP violation in the lepton sector, testing interaction models, and studying phenomena that have until now, seemed too complex to measure, like $\nu_\tau$ detection and therefore, providing the completion of the 3-flavor neutrino paradigm. Knowledge of the $\nu_\tau$ detection can impact a broad spectrum of open questions. These include searching for non-standard neutrino interactions, constraining the unitarity of the PMNS matrix, searching for sterile neutrinos, and studying neutrino interactions. In the case of LArTPC data, the detector hits can be considered nodes in a graph, and the edges represent the spatial and temporal relationships between them. By using graph neural networks, it is possible to exploit these relationships and improve the accuracy of particle identification and reconstruction. During my presentation and specifically for tau neutrino reconstruction, I will show the effectiveness and reliability of our in-house developed graph neural network (GNN), NuGraph. This GNN classifies detector hits based on the particle type responsible for their production, assuring that the system accurately identifies and categorizes information based on its unique characteristics.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

OpenACC Profiling Support for Clang and LLVM using Clacc and TAU

Since its launch in 2010, OpenACC has evolved into one of the most widely used portable programming models for accelerators on HPC systems today. Clacc is a project funded by the US Exascale Computing Project (ECP) to bring OpenACC support for C and C++ to the popular Clang and LLVM compiler infrastructure. In this paper, we describe Clacc's support for the OpenACC Profiling Interface, a critical component of the OpenACC specification that standardizes an interface that profiling tools and libraries can depend upon across OpenACC implementations. As part of Clacc's general strategy to build OpenACC support upon OpenMP, we describe how Clacc builds OpenACC Profiling Interface support upon an extended version of OMPT. We then describe how a major profiling and tracing toolkit within ECP, the TAU Performance System, takes advantage of this support. We also describe TAU's selective instrumentation support for OpenACC. Finally, using Clacc and TAU, we present example visualizations for several SPEC ACCEL OpenACC benchmarks running on an IBM AC922 node, and we show that the associated performance overhead is negligible.

Coti, Camille↗

Tau neutrinos in the next decade: from GeV to EeV

Tau neutrinos are the least studied particle in the standard model. This whitepaper discusses the current and expected upcoming status of tau neutrino physics with attention to the broad experimental and theoretical landscape spanning long-baseline, beam-dump, collider, and astrophysical experiments. This whitepaper was prepared as a part of the NuTau2021 Workshop.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Search for heavy neutral resonances decaying to tau lepton pairs in proton-proton collisions at $\sqrt{s}$=13 TeV

A search for heavy neutral gauge bosons (𝑍′) decaying into a pair of tau leptons is performed in proton-proton collisions at $\sqrt{s}$ =13 TeV at the CERN LHC. The data were collected with the CMS detector and correspond to an integrated luminosity of 138 fb −1 . The observations are found to be in agreement with the expectation from standard model processes. Limits at 95% confidence level are set on the product of the 𝑍′ production cross section and its branching fraction to tau lepton pairs for a range of 𝑍′ boson masses. For a narrow resonance in the sequential standard model scenario, a 𝑍′ boson with a mass below 3.5 TeV is excluded. This is the most stringent limit to date from this type of search.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Searches for Lepton Flavor Violation in Tau Decays at Belle II

Searches for lepton flavor violation in tau decays are unambiguous signatures of new physics. The branching ratios of tau leptons at the level of 10−10–10−9 can be probed using 50 ab−1 of electron-positron annihilation data being collected by the Belle II experiment at the world’s highest luminosity accelerator, the SuperKEKB, located at the High Energy Accelerator Research Organization, KEK, in Tsukuba, Japan. Searches with such expected sensitivity will either discover new physics or strongly constrain several new physics models.

79 ASTRONOMY AND ASTROPHYSICS↗

A multilayer network analysis of Alzheimer's disease pathogenesis: Roles for p‐tau, synaptic peptides, and physical activity

INTRODUCTION: In the aging brain, cognitive abilities emerge from the coordination of complex pathways arising from a balance between protective lifestyle and environmental factors and accumulation of neuropathologies. METHODS: As part of the Rush Memory and Aging Project (n = 440), we measured accelerometer-based actigraphy, cognitive performance, and after brain autopsy, selected reaction monitoring mass spectrometry. Multilevel network analysis was used to examine the relationships among the molecular machinery of vesicular neurotransmission, Alzheimer's disease (AD) neuropathology, cognition, and late-life physical activity. RESULTS: Synaptic peptides involved in neuronal secretory function were the most influential contributors to the multilayer network, reflecting the complex interdependencies among AD pathology, synaptic processes, and late-life cognition. Older adults with lower physical activity evidenced stronger adverse relationships among phosphorylated tau peptides, markers of synaptic integrity, and tangle pathology. DISCUSSION: Network-based approaches simultaneously model interdependent biological processes and advance understanding of the role of physical activity in age-associated cognitive impairment. Highlights: Network-based approaches simultaneously model interdependent biological processes. Secretory synaptic peptides were influential contributors to the multilayer network. Older adults with lower physical activity had adverse relationships among pathology. There was interdependence among phosphorylated tau, synaptic integrity, and tangles. Network methods elucidate the role of physical activity in cognitive impairment.

60 APPLIED LIFE SCIENCES↗

Search for top squark pair production in a final state with two tau leptons in proton-proton collisions at $ \sqrt{s} =$ 13 TeV

A search for pair production of the supersymmetric partner of the top quark, the top squark, in proton-proton collision events at $ \sqrt{s} $ = 13 TeV is presented in a final state containing hadronically decaying tau leptons and large missing transverse momentum. This final state is highly sensitive to high-tan β or higgsino-like scenarios in which decays of electroweak gauginos to tau leptons are dominant. The search uses a data set corresponding to an integrated luminosity of 77.2 fb$^{−1}$, which was recorded with the CMS detector during 2016 and 2017. No significant excess is observed with respect to the background prediction. Exclusion limits at 95% confidence level are presented in the top squark and lightest neutralino mass plane within the framework of simplified models, in which top squark masses up to 1100 GeV are excluded for a nearly massless neutralino.[graphic not available: see fulltext]

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Search for heavy neutral leptons in final states with electrons, muons, and hadronically decaying tau leptons in proton-proton collisions at $ \sqrt{s} $ = 13 TeV

A search for heavy neutral leptons (HNLs) of Majorana or Dirac type using proton-proton collision data at $ \sqrt{s} $ = 13 TeV is presented. The data were collected by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 138 fb$^{−1}$. Events with three charged leptons (electrons, muons, and hadronically decaying tau leptons) are selected, corresponding to HNL production in association with a charged lepton and decay of the HNL to two charged leptons and a standard model (SM) neutrino. The search is performed for HNL masses between 10 GeV and 1.5 TeV. No evidence for an HNL signal is observed in data. Upper limits at 95% confidence level are found for the squared coupling strength of the HNL to SM neutrinos, considering exclusive coupling of the HNL to a single SM neutrino generation, for both Majorana and Dirac HNLs. The limits exceed previously achieved experimental constraints for a wide range of HNL masses, and the limits on tau neutrino coupling scenarios with HNL masses above the W boson mass are presented for the first time.[graphic not available: see fulltext]

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Search for top squark pair production in a final state with at least one hadronically decaying tau lepton in proton-proton collisions at $ \sqrt{s} $ = 13 TeV

A search for pair production of the supersymmetric partner of the top quark, the top squark, in proton-proton collisions at $ \sqrt{s} $ = 13 TeV is presented in final states containing at least one hadronically decaying tau lepton and large missing transverse momentum. This final state is highly sensitive to scenarios of supersymmetry in which the decay of the top squark to tau leptons is enhanced. The search uses a data sample corresponding to an integrated luminosity of 138 fb$^{−1}$, which was recorded with the CMS detector during 2016–2018. No significant excess is observed with respect to the standard model predictions. Exclusion limits at 95% confidence level on the masses of the top squark and the lightest neutralino are presented under the assumptions of simplified models. The results probe top squark masses up to 1150 GeV for a nearly massless neutralino. This search covers a relatively less explored parameter space in the context of supersymmetry, and the exclusion limit is the most stringent to date for the model considered here.[graphic not available: see fulltext]

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Search for nonresonant Higgs boson pair production in final state with two bottom quarks and two tau leptons in proton-proton collisions at $\sqrt{s}$ = 13 TeV

A search for the nonresonant production of Higgs boson pairs (HH ) via gluon-gluon and vector boson fusion processes in final states with two bottom quarks and two tau leptons is presented. The search uses data from proton-proton collisions at a center-of-mass energy of $\sqrt{s}$ = 13 TeV recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb -1 . Events in which at least one tau lepton decays hadronically are considered and multiple machine learning techniques are used to identify and extract the signal. The data are found to be consistent, within uncertainties, with the standard model (SM) predictions. Upper limits on the HH production cross section are set to constrain the parameter space for anomalous Higgs boson couplings. The observed (expected) upper limit at 95% confidence level corresponds to 3.3 (5.2) times the SM prediction for the inclusive HH cross section and to 124 (154) times the SM prediction for the vector boson fusion HH cross section. At 95% confidence level, the Higgs field self-coupling is constrained to be within -1.7 and 8.7 times the SM expectation, and the coupling of two Higgs bosons to two vector bosons is constrained to be within -0.4 and 2.6 times the SM expectation.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Identification of tau leptons using a convolutional neural network with domain adaptation

A tau lepton identification algorithm,DeepTau, based on convolutional neural network techniques, has been developed in the CMS experiment to discriminate reconstructed hadronic decays of tau leptons (τ h ) from quark or gluon jets and electrons and muons that are misreconstructed as τ h candidates. The latest version of this algorithm, v2.5, includes domain adaptation by backpropagation, a technique that reduces discrepancies between collision data and simulation in the region with the highest purity of genuine τh candidates. Additionally, a refined training workflow improves classification performance with respect to the previous version of the algorithm, with a reduction of 30–50% in the probability for quark and gluon jets to be misidentified as τ h candidates for given reconstruction and identification efficiencies. This paper presents the novel improvements introduced in theDeepTau algorithm and evaluates its performance in LHC proton-proton collision data at √(s) = 13 and 13.6 TeV collected in 2018 and 2022 with integrated luminosities of 60 and 35 fb -1 , respectively. Techniques to calibrate the performance of the τ h identification algorithm in simulation with respect to its measured performance in real data are presented, together with a subset of results among those measured for use in CMS physics analyses.

Large detector-systems performance↗

Long-lived axionlike particles from tau decays

Axionlike particles (ALPs) are well-motivated examples of light, weakly coupled particles in theories beyond the Standard Model. In this work, we study long-lived ALPs coupled exclusively to leptons in the mass range between 2⁢𝑚 𝑒 and 𝑚 𝜏 − 𝑚 𝑒 . For anarchic flavor structure the leptophilic ALP production in tau decays or from ALP-tau bremsstrahlung is enhanced thanks to derivative couplings of the ALP and can surpass production from electron and muon channels, especially for ALPs heavier than 𝑚 𝜇 . Using past data from high-energy fixed-target experiments such as CHARM and BEBC we place new constraints on the ALP decay constant 𝑓 𝑎 , reaching scales as high as 𝒪⁡(10 8 ) GeV in lepton-flavor-violating channels and 𝑓 𝑎 ∼ 𝒪⁡(10 2 ) GeV in lepton-flavor-conserving ones. We also present projections for the event-rate sensitivity of current and future detectors to ALPs produced at the Fermilab Main Injector, the CERN SPS, and in the forward direction of the LHC. We show that SHiP will be sensitive to 𝑓 𝑎 values that are over an order of magnitude above the existing constraints.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗