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1. Fundamental Symmetries, Neutrons, and Neutrinos (FSNN): Whitepaper for the 2023 NSAC Long Range Plan

   Acharya, B; Adams, C; et, al (April 2023, arXiv:2304.03451)

   Whitepaper for the 2023 NSAC Long Range Plan 

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2. A Strategic Vision for Understanding Inter-Hemispheric Asymmetries

   https://doi.org/10.3847/25c2cfeb.21c7d275  

   Xu, Zhonghua; Lessard, Marc; Kim, Hyomin; Hartinger, Michael; Deng, Yue; Welling, Daniel; Öztürk, Doğacan; Chi, Peter; Halford, Alexa; Turner, Drew; et al (August 2023, The Bulletin of the American Astronomical Society)

   Vishniac, E; Muench, A (Ed.)

   Models for space weather forecasting will never be complete/valid without accounting for inter-hemispheric asymmetries in Earth’s magnetosphere, ionosphere and thermosphere. This whitepaper is a strategic vision for understanding these asymmetries from a global perspective of geospace research and space weather monitoring, including current states, future challenges, and potential solutions. 

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3. Search for excited tau leptons in the ττγ final state in proton-proton collisions at $$\sqrt{\text{s}}$$ = 13 TeV

   https://doi.org/10.1007/JHEP06(2025)006  

   Hayrapetyan, A; Tumasyan, A; Adam, W; Andrejkovic, J W; Benato, L; Bergauer, T; Chatterjee, S; Damanakis, K; Dragicevic, M; Hussain, P S; et al (June 2025, Journal of High Energy Physics)

   A<sc>bstract</sc> Results are presented for a test of the compositeness of the heaviest charged lepton,τ, using data collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 13 TeV at the CERN LHC. The data were collected in 2016–2018 and correspond to an integrated luminosity of 138 fb⁻¹. This analysis searches for tau lepton pair production in which one of the tau leptons is produced in an excited state and decays to a ground state tau lepton and a photon. The event selection consists of two isolated tau lepton decay candidates and a high-energy photon. The mass of the excited tau lepton is reconstructed using the missing transverse momentum in the event, assuming the momentum of the neutrinos from each tau lepton decay are aligned with the visible decay products. No excess of events above the standard model background prediction is observed. This null result is used to set lower bounds on the excited tau lepton mass. For a compositeness scale Λ equal to the excited tau lepton mass, excited tau leptons with masses below 4700 GeV are excluded at 95% confidence level; for Λ = 10 TeV this exclusion is set at 2800 GeV. This is the first experimental result covering this production and decay process in the excited tau mass range above 175 GeV. 

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4. Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions

   https://doi.org/10.7554/eLife.42571  

   Lin, Yanxian; McCarty, James; Rauch, Jennifer N; Delaney, Kris T; Kosik, Kenneth S; Fredrickson, Glenn H; Shea, Joan-Emma; Han, Songi (April 2019, eLife)

   Proteins make up much of the machinery of cells and perform many roles that are essential for life. Some important proteins – known as intrinsically disordered proteins – lack any stable three-dimensional structure. One such protein, called tau, is best known for its ability to form tangles in the brain, and a buildup of these tangles is a hallmark of Alzheimer’s disease and many other dementias. Tau is also one of a number of proteins that can undergo a process called liquid-liquid phase separation: essentially, a solution of tau separates into a very dilute solution interspersed with droplets of a concentrated tau solution, similar to an oil-water mixture separating into a very watery solution with drops of oil. Understanding the conditions that lead to spontaneous liquid-liquid phase separation might give insight into how the tau tangles form. However, it was not known whether it is possible in principle for liquid-liquid phase separation of tau to occur in a living brain. Lin, McCarty et al. have now used an advanced computer simulation method together with experiments to map the conditions under which a solution containing tau undergoes liquid-liquid phase separation. Temperature as well as the concentrations of salt and the tau protein all influenced how easily tau droplets formed or dissolved, and the narrow range of conditions that encouraged droplet formation fell within the normal conditions found in the body, also known as “physiological conditions”. This suggested that tau droplets might form and dissolve easily in living systems, and possibly in the brain, depending on the precise physiological conditions. To explore this possibility further, tau protein was added to a dish containing living cells. As the map suggested, slightly adjusting temperature or protein concentrations caused tau droplets to form and dissolve, all while the cells remained alive. The map provided by this study may offer guides to researchers looking for liquid-liquid phase separation in the brain. If liquid-liquid phase separation of tau occurs in living brains, it may be important for determining whether and when damaging tau tangles emerge. For example, the high concentration of tau in droplets might speed up tangle formation. Ultimately, a better understanding of the conditions and mechanism for liquid-liquid phase separation of tau can help researchers understand the role of protein droplet formation in living systems. This may be a process that promotes, or possibly a regulatory mechanism that prevents, the formation of tau tangles associated with dementia. 

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5. Joint Computational/Cell-Based Approach for Screening Inhibitors of Tau Oligomerization: A Proof-of-Concept Study

   https://doi.org/10.3233/JAD-220450  

   Man, Viet Hoang; Lin, Da; He, Xibing; Gao, Jie; Wang, Junmei (August 2022, Journal of Alzheimer's Disease)

   Background: Tau assembly produces soluble oligomers and insoluble neurofibrillary tangles, which are neurotoxic to the brain and associated with Alzheimer’s and Parkinson’s diseases. Therefore, preventing tau aggregation is a promising therapy for those neurodegenerative disorders. Objective: The aim of this study was to develop a joint computational/cell-based oligomerization protocol for screening inhibitors of tau assembly. Methods: Virtual oligomerization inhibition (VOI) experiment using molecular dynamics simulation was performed to screen potential oligomerization inhibitors of PHF6 hexapeptide. Tau seeding assay, which is directly related to the outcome of therapeutic intervention, was carried out to confirm a ligand’s ability in inhibiting tau assembly formation. Results: Our protocol was tested on two known compounds, EGCG and Blarcamesine. EGCG inhibited both the aggregation of PHF6 peptide in VOI and tau assembly in tau seeding assay, while Blarcamesine was not a good inhibitor at the two tasks. We also pointed out that good binding affinity to tau aggregates is needed, but not sufficient for a ligand to become a good inhibitor of tau oligomerization. Conclusion: VOI goes beyond traditional computational inhibitor screening of amyloid aggregation by directly examining the inhibitory ability of a ligand to tau oligomerization. Comparing with the traditional biochemical assays, tau seeding activities in cells is a better indicator for the outcome of a therapeutic intervention. Our hybrid protocol has been successfully validated. It can effectively and efficiently identify the inhibitors of amyloid oligomerization/aggregation processes, thus, facilitate to the drug development of tau-related neurodegenerative diseases. 

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