Showing papers by "University of Tokyo published in 2022"

Neutrophil extracellular traps regulate ischemic stroke brain injury

Abstract: Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice.

Abstract: Kaempferol, a flavonoid identified in a wide variety of dietary sources, has been reported to possess anti-obesity properties; however, its underlying mechanism was poorly understood. Chronic, low-grade gut inflammation and dysbacteria are proposed as underlying factors as well as novel treatment approaches for obesity-associated pathologies. This present study aims to investigate the benefits of experimental treatment with kaempferol on intestinal inflammation and gut microbial balance in animal model of obesity. High fat diet (HFD) was applied to C57BL/6J mice for 16 weeks, during which the supplement of kaempferol served as a variable. Clearly, HFD induced obesity, fat accumulation, glucose intolerance and adipose inflammation, the metabolic syndrome of which was the main finding. All these metabolic disorders can be alleviated through kaempferol supplementation. In addition, increased intestinal permeability, infiltration of immunocytes (macrophage, dendritic cells and neutrophils) and overexpression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1) were also found in the HFD-induced mice. Kaempferol supplementation improved intestinal barrier integrity and inhibited gut inflammation, by reducing the activation of TLR4/NF-κB pathway. Furthermore, the characterization of the cecal microbiota by sequencing showed that kaempferol supplementation was able to counteract the dysbiosis associated to obesity. Our study delineated the multiple mechanism of action underlying the anti-obesity effect of kaempferol, and provide scientific evidence to support the development of kaempferol as a dietary supplement for obesity treatment.

There is still plenty of room for layer-by-layer assembly for constructing nanoarchitectonics-based materials and devices

Abstract: Nanoarchitectonics approaches can produce functional materials from tiny units through combination of various processes including atom/molecular manipulation, chemical conversion, self-assembly/self-organization, microfabrication, and bio-inspired procedures. Existing fabrication approaches can be regarded as fitting into the same concept. In particular, the so-called layer-by-layer (LbL) assembly method has huge potential for preparing applicable materials with a great variety of assembling mechanisms. LbL assembly is a multistep process where different components can be organized in planned sequences while simple alignment options provide access to superstructures, for example helical structures, and anisotropies which are important aspects of nanoarchitectonics. In this article, newly-featured examples are extracted from the literature on LbL assembly discussing trends for composite functional materials according to (i) principles and techniques, (ii) composite materials, and (iii) applications. We present our opinion on the present trends, and the prospects of LbL assembly. While this method has already reached a certain maturity, there is still plenty of room for expanding its usefulness for the fabrication of nanoarchitectonics-based materials and devices.

Thermodynamic evidence for a field-angle-dependent Majorana gap in a Kitaev spin liquid

Abstract: The exactly solvable Kitaev model of two-dimensional honeycomb magnets has a quantum spin liquid phase characterized by the emergence of fractionalized Majorana fermion excitations. In the paramagnetic state of α-RuCl3 at high magnetic fields, a half-integer quantization of thermal Hall conductivity has been reported as a signature of edge currents carried by Majorana fermions, but the bulk nature of this state remains unconfirmed. Here, by measuring the heat capacity for different in-plane rotations of an applied magnetic field, we find strongly angle-dependent low-energy excitations in bulk α-RuCl3. The excitation gap has a sextuple node structure, and the gap amplitude increases with the field, as expected for itinerant Majorana fermions in the Kitaev model. Our thermodynamic observations of the opening and closing of the bulk gap according to the magnetic-field direction fully correspond with changes in the edge transport. Moreover, the behaviour at higher magnetic fields where the quantum thermal Hall effect vanishes is consistent with a nematic quantum spin liquid state with two-fold rotational symmetry. α-RuCl has a quantum magnetic phase that may be a spin liquid hosting Majorana fermion excitations. Heat capacity measurements show an anisotropic dependence on magnetic-field direction, consistent with predictions for the putative spin liquid.

Entropy, Divergence, and Majorization in Classical and Quantum Thermodynamics

Abstract: In these decades, it has been revealed that there is rich information-theoretic structure in thermodynamics of out-of-equilibrium systems in both the classical and quantum regimes. This has led to the fruitful interplay among statistical physics, quantum information theory, and mathematical theories including matrix analysis and asymptotic probability theory. The main purpose of this book is to clarify how information theory works behind thermodynamics and to shed modern light on it. We focus on both of purely information-theoretic concepts and their physical implications: We present self-contained and rigorous proofs of several fundamental properties of entropies, divergences, and majorization. We also discuss the modern formulations of thermodynamics, especially from the perspectives of stochastic thermodynamics and resource theory of thermodynamics. Resource theory is a recently-developed field as a branch of quantum information theory in order to quantify (energetically or information-theoretically) "useful resources." We show that resource theory has an intrinsic connection to various fundamental ideas of mathematics and information theory. This book is not intended to be a comprehensive review of the field, but would serve as a concise introduction to several important ingredients of the information-theoretic formulation of thermodynamics.

Antiferromagnetic Kitaev interaction in Jeff=1/2 cobalt honeycomb materials Na3Co2SbO6 and Na2Co2TeO6

Abstract: Finding new materials with antiferromagnetic (AFM) Kitaev interaction is an urgent issue for quantum magnetism research. We conclude that Na3Co2SbO6 and Na2Co2TeO6 are new honeycomb cobalt-based systems with AFM Kitaev interaction by carrying out inelastic neutron scattering experiments and subsequent analysis. The spin-orbit excitons observed at 20-28 meV in both compounds strongly support the idea that Co2+ ions of both compounds have a spin-orbital entangled Jeff=1/2 state. Furthermore, we found that a generalized Kitaev-Heisenberg Hamiltonian can describe the spin-wave excitations of both compounds with additional 3rd nearest-neighbor interaction. Our best-fit parameters show significant AFM Kitaev terms and off-diagonal symmetric anisotropy terms of a similar magnitude in both compounds. We also found a strong magnon-damping effect at the higher energy part of the spin waves, entirely consistent with observations in other Kitaev magnets. Our work suggests Na3Co2SbO6 and Na2Co2TeO6 as rare examples of the AFM Kitaev magnets based on the systematic studies of the spin waves and analysis.

PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.

Abstract: Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate lipid countertransport, in which two distinct lipids are transported counterdirectionally. How such lipid countertransport controls specific biological functions, however, remains elusive. We report that lipid countertransport by ORP10 at ER-endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed ER-endosome MCSs in a phosphatidylinositol 4-phosphate (PI4P)-dependent manner. ORP10 exhibited a lipid exchange activity toward its ligands, PI4P and phosphatidylserine (PS), between liposomes in vitro, and between the ER and endosomes in situ. Cell biological analysis demonstrated that ORP10 supplies a pool of PS from the ER, in exchange for PI4P, to endosomes where the PS-binding protein EHD1 is recruited to facilitate endosome fission. Our study highlights a novel lipid exchange at ER-endosome MCSs as a nonenzymatic PI4P-to-PS conversion mechanism that organizes membrane remodeling during retrograde membrane trafficking.

Magnitude, frequency and climate forcing of global volcanism during the last glacial period as seen in Greenland and Antarctic ice cores (60–9 ka)

Abstract: Abstract. Large volcanic eruptions occurring in the last glacial period can be detected by their accompanying sulfuric acid deposition in continuous ice cores. Here we employ continuous sulfate and sulfur records from three Greenland and three Antarctic ice cores to estimate the emission strength, the frequency and the climatic forcing of large volcanic eruptions that occurred during the second half of the last glacial period and the early Holocene, 60–9 kyr before 2000 CE (b2k). Over most of the investigated interval the ice cores are synchronized, making it possible to distinguish large eruptions with a global sulfate distribution from eruptions detectable in one hemisphere only. Due to limited data resolution and large variability in the sulfate background signal, particularly in the Greenland glacial climate, we only list Greenland sulfate depositions larger than 20 kg km−2 and Antarctic sulfate depositions larger than 10 kg km−2. With those restrictions, we identify 1113 volcanic eruptions in Greenland and 737 eruptions in Antarctica within the 51 kyr period – for which the sulfate deposition of 85 eruptions is found at both poles (bipolar eruptions). Based on the ratio of Greenland and Antarctic sulfate deposition, we estimate the latitudinal band of the bipolar eruptions and assess their approximate climatic forcing based on established methods. A total of 25 of the identified bipolar eruptions are larger than any volcanic eruption occurring in the last 2500 years, and 69 eruptions are estimated to have larger sulfur emission strengths than the Tambora, Indonesia, eruption (1815 CE). Throughout the investigated period, the frequency of volcanic eruptions is rather constant and comparable to that of recent times. During the deglacial period (16–9 ka b2k), however, there is a notable increase in the frequency of volcanic events recorded in Greenland and an obvious increase in the fraction of very large eruptions. For Antarctica, the deglacial period cannot be distinguished from other periods. This confirms the suggestion that the isostatic unloading of the Northern Hemisphere (NH) ice sheets may be related to the enhanced NH volcanic activity. Our ice-core-based volcanic sulfate records provide the atmospheric sulfate burden and estimates of climate forcing for further research on climate impact and understanding the mechanism of the Earth system.

First gadolinium loading to Super-Kamiokande

Abstract: In order to improve Super-Kamiokande’s neutron detection efficiency and to thereby increase its sensitivity to the diffuse supernova neutrino background flux, 13 tons of Gd2(SO4)3⋅8H2O (gadolinium sulfate octahydrate) was dissolved into the detector’s otherwise ultrapure water from July 14 to August 17, 2020, marking the start of the SK-Gd phase of operations. During the loading, water was continuously recirculated at a rate of 60 m3/h, extracting water from the top of the detector and mixing it with concentrated Gd2(SO4)3⋅8H2O solution to create a 0.02% solution of the Gd compound before injecting it into the bottom of the detector. A clear boundary between the Gd-loaded and pure water was maintained through the loading, enabling monitoring of the loading itself and the spatial uniformity of the Gd concentration over the 35 days it took to reach the top of the detector. During the subsequent commissioning the recirculation rate was increased to 120 m3/h, resulting in a constant and uniform distribution of Gd throughout the detector and water transparency equivalent to that of previous pure-water operation periods. Using an Am–Be neutron calibration source the mean neutron capture time was measured to be 115±1 μs, which corresponds to a Gd concentration of 111±2 ppm, as expected for this level of Gd loading. This paper describes changes made to the water circulation system for this detector upgrade, the Gd loading procedure, detector commissioning, and the first neutron calibration measurements in SK-Gd.

An explainable recommendation framework based on an improved knowledge graph attention network with massive volumes of side information

Abstract: In recent years, explainable recommendation has been a topic of active study. This is because the branch of the machine learning field related to methodologies is enabling human understanding of the reasons for the outputs of recommender systems. The realization of explainable recommendation is widely expected to increase both user satisfaction and the demand for explainable recommendation systems. Explainable recommendation utilizes a wealth of side information (such as sellers, brands, user ages and genders, and bookmark information, among others) to expound the decision-making reasoning applied by recommendation models. In explainable recommendation, although learning side information containing numerous variables leads to rich interpretability, learning too many variables presents a challenge because decreases the amount of learning that a given computational resource can perform, and the accuracy of the recommendation model may be degraded. However, numerous and diverse variables are included in the side information stored by the actual companies operating massive real-world services. Hence, to realize practical applications of this valuable information, it is necessary to resolve problems such as computational cost. In this study, we propose a new framework for explainable recommendation based on an improved knowledge graph attention network model, which utilizes the side information of items and realizes high recommendation accuracy. The proposed framework enables direct interpretation by visualizing the reasons for the recommendations provided. Experimental results show that the proposed framework reduced computational time requirements by approximately 80%, while maintaining recommendation accuracy by enabling the model to learn the probabilistically given edges included in the graph structure. Moreover, the results show that the proposed framework exhibited richer interpretability than the conventional model. Finally, a multifaceted analysis suggests that the proposed framework is not only effective as an explainable recommendation model but also provides a powerful tool for planning various marketing strategies. • Reduced the computational cost of knowledge graph enabled recommendation. • Improved explainability while maintaining high recommendation accuracy. • Introduced how to apply knowledge graph embedding to marketing strategy planning. • Presented strengths of explainable recommendation, not just explainability. • Improved value and applicability of knowledge graph attention network to services.

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Abstract: Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully-coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow the frequency and frequency time-derivative of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets.