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Alzheimer’s disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used theApp^{NL-G-F/NL-G-F}knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein (APP) gene with three familial AD mutations. We performedin vivodiffusion tensor imaging (DTI) to study how the structural properties of the brain change across age in the context of AD. In late age APPKI mice, we observed reduced fractional anisotropy (FA), a proxy of WM integrity, in multiple brain regions, including the hippocampus, anterior commissure (AC), neocortex, and hypothalamus. At the cellular level, we observed greater numbers of oligodendrocytes in middle age (prior to observations in DTI) in both the AC, a major interhemispheric WM tract, and the hippocampus, which is involved in memory and heavily affected in AD, prior to observations in DTI. Proteomics analysis of the hippocampus also revealed altered expression of oligodendrocyte-related proteins with age and in APPKI mice. Together, these results help to improve our understanding of the development of AD pathology with age, and imply that middle age may be an important temporal window for potential therapeutic intervention. 

Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD. Methods To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations ( App NL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age. Results We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice. Discussion Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD. 

Abstract The Jiangmen Underground Neutrino Observatory (JUNO) is a large-scale neutrino experiment with multiple physics goals including determining the neutrino mass hierarchy, the accurate measurement of neutrino oscillation parameters, the neutrino detection from supernovae, the Sun, and the Earth, etc. JUNO puts forward physically and technologically stringent requirements for its central detector (CD), including a large volume and target mass (20 kt liquid scintillator, LS), a high-energy resolution (3% at 1 MeV), a high light transmittance, the largest possible photomultiplier (PMT) coverage, the lowest possible radioactive background, etc. The CD design, using a spherical acrylic vessel with a diameter of 35.4 m to contain the LS and a stainless steel structure to support the acrylic vessel and PMTs, was chosen and optimized. The acrylic vessel and the stainless steel structure will be immersed in pure water to shield the radioactive background and bear great buoyancy. The challenging requirements of the acrylic sphere have been achieved, such as a low intrinsic radioactivity and high transmittance of the manufactured acrylic panels, the tensile and compressive acrylic node design with embedded stainless steel pad, and one-time polymerization for multiple bonding lines. Moreover, several technical challenges of the stainless steel structure have been solved: the production of low radioactivity stainless steel material, the deformation and precision control during production and assembly, and the usage of high-strength stainless steel rivet bolt and of high friction efficient linkage plate. Finally, the design of the ancillary equipment such as the LS filling, overflowing, and circulating system was done. 

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g.,$$n\rightarrow 3 \nu $$ $n\to 3\nu$or$$nn \rightarrow 2 \nu $$ $nn\to 2\nu$), which do not produce an observable signal. The invisible decay includes two decay modes:$$ n \rightarrow { inv} $$ $n\to \mathrm{inv}$and$$ nn \rightarrow { inv} $$ $nn\to \mathrm{inv}$. The invisible decays ofs-shell neutrons in$$^{12}\textrm{C}$$ $_{}^{12}\text{C}$will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino$${\bar{\nu }}_e$$ ${\overline{\nu }}_e$, natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are$$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ $\tau /B(n\to \mathrm{inv})>5.0\times {10}^{31}\text{years}$and$$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ $\tau /B(nn\to \mathrm{inv})>1.4\times {10}^{32}\text{years}$. 

Abstract The physics potential of detecting⁸B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of¹³C nuclei in the liquid scintillator detectors and the expected low background level,⁸B solar neutrinos are observable in the CC and NC interactions on¹³C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the⁸B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1σprecision levels of 5%, 8%, and 20% for the⁸B neutrino flux, ${\sin }^2{\theta }_{12}$, and $\mathrm{\Delta }{m}_{21}^2$, respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the⁸B neutrino flux. 

Abstract The core-collapse supernova (CCSN) is considered one of the most energetic astrophysical events in the universe. The early and prompt detection of neutrinos before (pre-SN) and during the supernova (SN) burst presents a unique opportunity for multi-messenger observations of CCSN events. In this study, we describe the monitoring concept and present the sensitivity of the system to pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton liquid scintillator detector currently under construction in South China.The real-time monitoring system is designed to ensure both prompt alert speed and comprehensive coverage of progenitor stars. It incorporates prompt monitors on the electronic board as well as online monitors at the data acquisition stage.Assuming a false alert rate of 1 per year, this monitoring system exhibits sensitivity to pre-SN neutrinos up to a distance of approximately 1.6 (0.9) kiloparsecs and SN neutrinos up to about 370 (360) kiloparsecs for a progenitor mass of 30 solar masses, considering both normal and inverted mass ordering scenarios.The pointing ability of the CCSN is evaluated by analyzing the accumulated event anisotropy of inverse beta decay interactions from pre-SN or SN neutrinos. This, along with the early alert, can play a crucial role in facilitating follow-up multi-messenger observations of the next galactic or nearby extragalactic CCSN. 

Abstract The Jiangmen Underground Neutrino Observatory (JUNO), the first multi-kton liquid scintillator detector, which is under construction in China, will have a unique potential to perform a real-time measurement of solar neutrinos well below the few MeV threshold typical of Water Cherenkov detectors. JUNO's large target mass and excellent energy resolution are prerequisites for reaching unprecedented levels of precision. In this paper, we provide estimation of the JUNO sensitivity to⁷Be,pep, and CNO solar neutrinos that can be obtained via a spectral analysis above the 0.45 MeV threshold. This study is performed assuming different scenarios of the liquid scintillator radiopurity, ranging from the most optimistic one corresponding to the radiopurity levels obtained by the Borexino experiment, up to the minimum requirements needed to perform the neutrino mass ordering determination with reactor antineutrinos — the main goal of JUNO. Our study shows that in most scenarios, JUNO will be able to improve the current best measurements on⁷Be,pep, and CNO solar neutrino fluxes. We also perform a study on the JUNO capability to detect periodical time variations in the solar neutrino flux, such as the day-night modulation induced by neutrino flavor regeneration in Earth, and the modulations induced by temperature changes driven by helioseismic waves. 

Abstract We discuss JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo via detecting inverse beta decay reactions of electron anti-neutrinos resulting from the annihilation. We study possible backgrounds to the signature, including the reactor neutrinos, diffuse supernova neutrino background, charged- and neutral-current interactions of atmospheric neutrinos, backgrounds from muon-induced fast neutrons and cosmogenic isotopes. A fiducial volume cut, as well as the pulse shape discrimination and the muon veto are applied to suppress the above backgrounds. It is shown that JUNO sensitivity to the thermally averaged dark matter annihilation rate in 10 years of exposure would be significantly better than the present-day best limit set by Super-Kamiokande and would be comparable to that expected by Hyper-Kamiokande. 

Abstract Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20 kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3% at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK).