Search

β-Hydroxy-β-methylbutyrate (HMB) is an intermediate in the metabolism of the branched-chain amino acid leucine. HMB has several demonstrated effects on skeletal muscle function, some of which are contradictory. In addition, the effect of exogenous HMB intake on the levels of intermediate metabolites is not known. Therefore, we investigated changes in HMB metabolites after oral HMB administration in mice. First, ICR mice were treated with either distilled water or HMB (0.215 g/10 mL/kg). Sampling was performed at 0, 1, 6, 12, and 24 h after administration. Next, ICR mice were given distilled water or HMB (0.215 g/10 mL/kg/d) for 10 d. Mice given HMB shown a significant increase in liver β-methylcrotonyl-CoA and increased β-hydroxybutyrate in plasma and the gastrocnemius muscle 1 h after HMB administration. Mice administered HMB for 10 d showed significantly decreased food intake and body weight; however, the relative weight of the gastrocnemius muscle was significantly increased. These results may be attributed to an increase in β-hydroxybutyrate resulting from exogenous HMB, since β-hydroxybutyrate inhibits food intake and suppresses skeletal muscle catabolism. In conclusion, β-hydroxybutyrate, a metabolite of HMB, was found to play an important role in the function of HMB., Highlights • β-Hydroxybutyrate levels in plasma and gastrocnemius were enhanced by HMB. • HMB increases in tissues and plasma returned to original levels within 6 h. • HMB treatment for 10 d suppressed food intake and decreased body weight. • Gastrocnemius weight was increased despite deceased body weight in HMB-treated mice.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Additionally, the efficacy of targeted molecular therapies with multiple tyrosine kinase inhibitors is limited. In this study, we focused on the cellular signaling pathways common to diverse HCC cells and used quantitative reverse phase protein array (RPPA) and statistical analyses to elucidate the molecular mechanisms determining its malignancy. We examined the heterogeneity of 17 liver cancer cell lines by performing cluster analysis of their expression of CD90 and EpCAM cancer stem cell markers. Gaussian mixture model clustering identified three dominant clusters: CD90-positive and EpCAM-negative (CD90+), EpCAM-positive and CD90-negative (EpCAM+) and EpCAM-negative and CD90-negative (Neutral). A multivariate analysis by partial least squares revealed that the former two cell populations showed distinct patterns of protein expression and phosphorylation in the EGFR and EphA2 signaling pathways. The CD90+ cells exhibited higher abundance of AKT, EphA2 and its phosphorylated form at Ser897, whereas the EpCAM+ cells exhibited higher abundance of ERK, RSK and its phosphorylated form. This demonstrates that pro-oncogenic, ligand-independent EphA2 signaling plays a dominant role in CD90+ cells with higher motility and metastatic activity than EpCAM+ cells. We also showed that an AKT inhibitor reduced the proliferation and survival of CD90+ cells but did not affect those of EpCAM+ cells. Taken together, our results suggest that AKT activation may be a key pro-oncogenic regulator in HCC.

We explore the hyperbolic band theory under a magnetic field for the first time. Our theory is a general extension of the conventional band theory defined on a Euclidean lattice into the band theory on a general hyperbolic lattice/Riemann surface. Our methods and results can be confirmed experimentally by circuit quantum electrodynamics (cQED), which enables us to create novel materials in a hyperbolic space. To investigate the band structures, we construct directly the hyperbolic magnetic Bloch states and find that they form Dirac cones on a coordinate neighborhood, by which they can be regarded as a global quantum gravity solution detectable in a laboratory. Besides this is the first explicit example of a massless Dirac state on a higher genus surface. Moreover we show that the energy spectrum exhibits an unusual fractal structure refracting the negative curvature, when plotted as a function of a magnetic flux., 7 pages, 3 figures

The real-time topological susceptibility is studied in $(1+1)$-dimensional massive Schwinger model with a $\theta$-term. We evaluate the real-time correlation function of electric field that represents the topological Chern-Pontryagin number density in $(1+1)$ dimensions. Near the parity-breaking critical point located at $\theta=\pi$ and fermion mass $m$ to coupling $g$ ratio of $m/g \approx 0.33$, we observe a sharp maximum in the topological susceptibility. We interpret this maximum in terms of the growth of critical fluctuations near the critical point, and draw analogies between the massive Schwinger model, QCD near the critical point, and ferroelectrics near the Curie point., Comment: 9 pages, 5 figures

We explore quantum phase transitions using two probes of quantum chaos: out-of-time-order correlators (OTOCs) and the $r$-parameter obtained from the level spacing statistics. In particular, we address $p$-spin models associated with quantum annealing or reverse annealing. Quantum annealing triggers first-order or second-order phase transitions, which is crucial for the performance of quantum devices. We find that the time-averaging OTOCs for the ground state and the average $r$-parameter change behavior around the corresponding transition points, diagnosing the phase transition. Furthermore, they can identify the order (first or second) of the phase transition by their behavior at the quantum transition point, which changes abruptly (smoothly) in the case of first-order (second-order) phase transitions., 22 pages, 23 figures

Recent progress in human induced pluripotent stem cells (iPSC) technologies suggest that iPSC application in regenerative medicine is a closer reality. Numerous challenges prevent iPSC application in the development of numerous tissues and for the treatment of various diseases. A key concern in therapeutic applications is the safety of the cell products to be transplanted into patients. Here, we present novel method for detecting residual undifferentiated iPSCs amongst directed differentiated cells of all three germ lineages. Marker genes, which are expressed specifically and highly in undifferentiated iPSC, were selected from single cell RNA sequence data to perform robust and sensitive detection of residual undifferentiated cells in differentiated cell products. ESRG (Embryonic Stem Cell Related), CNMD (Chondromodulin), and SFRP2 (Secreted Frizzled Related Protein 2) were well-correlated with the actual amounts of residual undifferentiated cells and could be used to detect residual cells in a highly sensitive manner using qPCR. In addition, such markers could be used to detect residual undifferentiated cells from various differentiated cells, including hepatic cells and pancreatic cells for the endodermal lineage, endothelial cells and mesenchymal cells for the mesodermal lineage, and neural cells for the ectodermal lineage. Our method facilitates robust validation and could enhance the safety of the cell products through the exclusion of undifferentiated iPSC., Scientific Reports, 10 (1), ISSN:2045-2322

The Langlands program is a vast mathematical projection linking number theory and geometry. In high-energy physics, a connection with mirror symmetry has been suggested in string theory, but it has been little studied in low-energy physics. In the framework of the Langlands program, we present a unified description of the integer and fractional quantum Hall effect and the duality found in the fractal nature of the energy spectrum of two-dimensional block electrons, statistical physics, and quantum computation. The new unified view of existing dualism presented in this paper raises the entirely new question of how each theory of physics is connected as a piece of the Langlands program.

We report the case of a 78-year-old woman with methotrexate-related gastric lymphoproliferative disorder (LPD). The patient had a history of rheumatoid arthritis (RA) and had been treated with methotrexate (MTX). Endoscopic examination revealed round elevated lesions in the stomach, and a biopsy specimen showed atypical lymphoid cell proliferation. Immunohistological study found these atypical cells to be positive for L-26 but not for CD3 or EBER. Therefore, we made a diagnosis of MTX-related LPD showing features of diffuse large B-cell lymphoma. Combined positron emission tomography-computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) showed increased avidity in the stomach in addition to slightly increased FDG-avidity in the mediastinum and left chest wall. We decided not to start chemotherapy but to discontinue administration of MTX, with follow-up using endoscopy and PET-CT. The endoscopic examinations after cessation of MTX demonstrated gradual regression of the elevated lesions. PET-CT 6 months after cessation showed no increased FDG avidity in the stomach. While disease regression was observed in the stomach, the other FDG-avid spots remained unchanged on PET-CT. Therefore, we performed chemotherapy as additional therapy. On PET-CT after chemotherapy, the FDG-avid spots remained unchanged for more than 1 year, and we eventually concluded that they were RA-related inflammatory lesions. In patients with MTX-related LPD, cessation of MTX may be a therapeutic option, but careful follow-up and chemotherapy in accordance with the clinical course are essential.

We address the energy spectrum of honeycomb lattice with various defects or impurities under a perpendicular magnetic field. We use a tight-binding Hamiltonian including interactions with the nearest neighbors and investigate its energy structure for two different choices of point defects or impurities. In the first case, we fix a unit cell consisting of 8 lattice points and survey the energy eigenvalues in the presence of up to 2 point defects. Then it turns out that the existence of the fractal energy structure, called Hofstadter's butterfly, depends on the choice of defect pairs. In the second case, we extend the size of a unit cell which contains a single point defect and up to 32 lattice points. The fractal structures indeed appear for those cases and there exist a robust gapless point in the $E=0$ eV line without depending on both the size of unit cells and the shape of lattices. Therefore we keep an immortal butterfly since such a robust point corresponds to the center of a butterfly. Consequently we predict that the presence of a butterfly in a graph is equivalent to that of fractality., 8 pages, 19 figures

Recent advances in the Langlands program shed light on a vast area of modern mathematics from an unconventional viewpoint, including number theory, gauge theory, representation, knot theory and etc. By applying to physics, these novel perspectives endow with a unified account of the (integer/ fractional) quantum Hall effect. The plateaus of the Hall conductance are described by Hecke eigensheaves of the geometric Langlands correspondence. Especially, the particle-vortex duality, which is explained by S-duality of Chern-Simons theory, corresponds to the Langlands duality in Wilson and Hecke operators. Moreover the Langlands duality in the quantum group associated with the Hamiltonian describes fractal energy spectrum structure, know as Hofstadter's butterfly. These results suggest that the Langlands program has many physically realistic meanings., 21 pages, 4 figures

Coastal landfill sites not only offer an option for disposal but also create a new land space after the completion of landfilling. To perform proper design on settlement, stability, and/or bearing capacity at landfill sites, the geotechnical properties of the waste layer such as deformation and shear strength should be investigated. This research is focused on the mechanical properties of waste mixture sampled at a coastal landfill site including municipal solid waste incinerator ash, slag, soil and others, to provide useful information on geotechnical properties in utilizing coastal landfill sites after their closure. A series of triaxial consolidated undrained compression tests (CU) and hydraulic conductivity tests were carried out on the reconstituted waste samples before and after being cured in simulated leachate water in coastal landfill sites for different periods, to understand the aging effects on mechanical properties of waste mixture. It was shown that while curing results in an increase in the peak strength and deformation modulus, the residual strength was not affected by the curing periods. Scanning electron microscope observations and X-ray diffraction analysis on the waste samples after curing confirmed that the formation of ettringite and hydration products had a densification effect on the microstructure. The higher peak shear strength and lower hydraulic conductivity of the waste samples were attributed to this effect.