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Strategies to develop cancer therapies using inhibitors that target matrix metalloproteinases (MMPs), particularly membrane type-1 MMP (MT1-MMP), have failed. This is predominantly attributed to the specificity of MMP inhibitors and numerous functions of MMPs; therefore, targeting substrates with such broad specificity can lead to off-target effects. Thus, new drug development for cancer therapeutics should focus on the ability of MT1-MMP to break down substrates, such as functional cell membrane proteins, to regulate the functions of these proteins that promote tumor malignancy. In this review, we discuss the mechanism by which proteolysis of cell surface proteins by MT1-MMP promotes progression of malignant tumor cells. In addition, we discuss the two protein fragments generated by limited cleavage of erythropoietin-producing hepatoma receptor tyrosine kinase A2 (EphA2-NF, -CF), which represent a promising basis for developing new cancer therapies and diagnostic techniques.

Quantum field theory can be a new medium for communication through quantum energy teleportation. We perform a demonstration of quantum energy teleportation with a relativistic fermionic field theory of self-coupled fermions, called the massive Thirring model. Our results reveal that there is a close relationship between the amount of energy teleported and the phase diagram of the theory. In particular, we show that the teleported energy peaks near the phase transition points. Since these results are obtained by measuring the two local subsystems, the noise from the quantum computation can be considerably reduced, allowing for efficient quantum simulations. Moreover, it is a new entanglement-based method that reveals global structure through local measurements.

Dynamic covalent bonds are useful tools in a wide range of applications. Although various reversible chemical reactions have been studied for this purpose, the requirement for harsh conditions, such as high temperature and low or high pH, to activate generally stable covalent bonds limits their potential applications involving biomolecules or household utilization. Here, we report the design, synthesis, characterization, and dynamic covalent bonding properties of 1,2-disubstituted 1,2-dihydro-1,2,4,5-tetrazine-3,6-dione (TETRAD). Hetero-Diels-Alder reactions of TETRAD with furan derivatives and their retro-reactions proceeded rapidly at room temperature under neutral conditions, enabling a chemically induced sol-gel transition system.

Teleporting physical quantities to remote locations is a remaining key challenge for quantum information science and technology. Quantum teleportation has enabled the transfer of quantum information, but teleportation of quantum physical quantities has not yet been realized. Here we report the first realization and observation of quantum energy teleportation on real quantum hardware. We achieve this by using several IBM’s superconducting quantum computers. The results are consistent with the exact solution of the theory and are improved by the mitigation of measurement error. Quantum energy teleportation requires only local operations and classical communication. Therefore our results provide a realistic benchmark that is fully achievable with current quantum computing and communication technologies.

This In recent years, the demand and supply of energy has been changing rapidly. Renewable energies have attracted attention worldwide, because they are deemed suitable to realizing a decarbonized society; thus, they are being researched and developed actively. However, the amount of electricity generated by distributed power sources using renewable energy is extremely unstable, and in addition to adjusting the supply-demand balance using base-load power sources and regulating thermal power, it is necessary to adjust the demand for electricity on the consumer side.In this work, data were obtained to conduct a basic study of demand adjustment on the consumer side; in addition, a basic study of the correlation between each element related to air conditioning equipment was conducted to investigate what kind of influence determines the power consumption of air conditioning equipment. The data used comprised moving averages (excluding weekends, which are unoccupied holidays).As a result, a separate correlation was obtained between the operating hours of air-conditioning equipment and outdoor temperature around 15°C. The correlation coefficient below 15°C was found to be -0.7577, while the correlation coefficient above 15°C was 0.7712. The data confirmed that people feel hotter or colder when the temperature is further away from 15°C. Therefore, temperatures around 15℃ were found to be the most comfortable.

In recent years, the use of distributed power sources, such as photovoltaic power generators and fuel cells, has become widespread. In particular, next-generation power distribution systems for residences based on direct current (DC) power supply and distribution are being actively researched in Japan. In this context, this paper investigates the effects of operating home appliances with a DC power supply using a special winding transformer on each device were investigated. To this end, a smart house equipped with DC power supplied by a transformer with a special winding structure was configured. Experimental observations confirmed that all digital home appliances exhibited proper functions on the aforementioned DC power architecture.

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.

Viewing quantum information as economic commodity, we provide a fundamental viewpoint toward a quantum theory of contracts. In particular, a generic quantum protocol of the principal–agent relation is formulated in a framework of quantum games, and quantum models of moral hazard problem and adverse selection are addressed. New infrastructures are about to be created by the development of quantum technology, which will have a revolutionary impact on people’s economic activities. In other words, the time will come in the near future when people will conduct their economic activities on the complex Hilbert space. However, this kind of economic activity is not envisioned at all in conventional economics, so a new theory is literally needed. These problems include public and private interests of exchanging quantum commodity, market design and contracts, for example. In this article, We present a quantum contract theory based on this new fulcrum, and solve the problem of information asymmetry between principal and agent, which has long been a central issue in classical contract theory.

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.

In this paper, a 24-pulse converter with a transformer using a special winding structure was fabricated and its efficiency, output voltage ripple and harmonics were compared with those of 6-pulse and 12-pulse converters.

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Enantioselective C–H functionalization reactions using trivalent group 9 metals (Co, Rh, Ir) have been investigated mainly on the basis of the development of well-designed chiral cyclopentadienyl (...

BACKGROUND/PURPOSE The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P

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 investigate the electronic properties in the Bloch electron on a square lattice with vacancies in the uniform magnetic field. We show that a single vacancy site introduced to the system creates a defect energy level in every single innumerable fractal energy gap in the Hofstadter butterfly. The wavefunctions of different defect levels have all different localization lengths depending on their fractal generations, and they can be described by a single universal function after an appropriate fractal scaling. We also show that each defect state has its own characteristic orbital magnetic moment, which is exactly correlated to the gradient of the energy level in the Hofstadter diagram. Probing the spatial nature of the defect-localized states provides a powerful way to elucidate the fractal nature of the Hofstadter butterfly., Comment: 10 pages, 10 figures

Advances in organoid technology have broadened the number of target diseases and conditions in which human induced pluripotent stem cell (iPSC)-based regenerative medicine can be applied; however, mass production of organoids and the development of chemically defined, animal origin-free (CD-AOF) media and supplements are unresolved issues that hamper the clinical applicability of these approaches. CD-AOF media and supplements ensure the quality and reproducibility of culture systems by lowering lot-to-lot variations and the risk of contamination with viruses or toxins. We previously generated liver organoids from iPSCs, namely iPSC-liver buds (iPSC-LBs), by mimicking the organogenic interactions among hepatocytes, endothelial cells (ECs), and mesenchymal cells (MCs) and recently reported the mass production of iPSC-LBs derived entirely from iPSCs (all iPSC-LBs), which should facilitate their large-scale production for the treatment of liver failure. However, in previous studies we used media originating from animals for differentiation except for the maintenance of undifferentiated iPSCs. Therefore, we developed a CD-AOF medium to generate all iPSC-LBs. We first developed a CD-AOF medium for hepatocytes, ECs, and stage-matched MCs, i.e., septum transversum mesenchyme (STM), in 2D cultures. We next generated all iPSC-LBs by incubating individual cell types in ultra-low attachment micro-dimple plates. The hepatic functions of all iPSC-LBs generated using the CD-AOF medium were equivalent to those of all iPSC-LBs generated using the conventional medium both in vitro and in vivo. Furthermore, we found that this CD-AOF medium could be used in several cell culture settings. Taken together, these results demonstrate the successful development of a CD-AOF medium suitable for all iPSC-LBs. The protocol developed in this study will facilitate the clinical applicability of all iPSC-LBs in the treatment of liver diseases.

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

In this paper, we advocate utilizing link–level broadcast of wireless LAN (WLAN) for real–time data transmissions from a drone to ground access points (APs) in order to enhance their robustness and spectral efficiency. A WLAN station (STA) is installed on a drone, which broadcasts its real-time data to surrounding multi–APs deployed over a ground field. In order to enhance the reliability of data transmissions, we also apply packet–level forward error correction (FEC). We conduct a field trial with our experimental testbed where all the above functions are implemented into the off–the–shelf WLAN equipment. Our experimental results show that multi–AP broadcast transmissions with packet–level FEC achieve better packet delivery ratio with smaller channel occupancy period than a common approach utilizing unicast transmissions.

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

Repeated quantum game theory addresses long term relations among players who choose quantum strategies. In the conventional quantum game theory, only single round quantum games or at most finitely repeated games have been studied, therefore nothing is known for infinitely repeated quantum game. Investigating infinitely repeated games is crucial since finitely repeated games do not much differ from single round games. In this work we establish the concept of general repeated quantum games and show the Quantum Folk Theorem, which claims that by iterating a game one can find an equilibrium strategy of the game and receive reward that is not obtained by a Nash equilibrium of the corresponding single round quantum game. A significant difference between repeated quantum prisoner's dilemma and repeated classical prisoner's dilemma is that the classical Pareto optimal solution is not always an equilibrium of the repeated quantum game when entanglement is sufficiently strong. In addition we present several concrete equilibrium strategies of the repeated quantum prisoner's dilemma.

New types of macrocyclic compounds, deltaarenes, are prepared. The compounds were readily synthesized in three steps from an arenedithiol and benzoquinone, and the yields of the macrocyclization reaction reached up to 40% under high dilution conditions. X-ray crystallographic analysis revealed that the macrocycle has a relatively rigid trimeric structure with a unique triangular hole, the size of which was approximately 11 A along each side. NMR data suggests that the ring has a C3-symmetric structure. The X-ray analysis showed that the hole is large enough to capture one molecule of chlorobenzene. Use of a variety of dithiols allowed the synthesis of different types of deltaarene derivatives. MO calculations showed that the hole size depends on the dithiol unit. Deprotection of the twelve methoxyl groups was easily achieved by treatment with BBr3 and yielded the free-OH deltaarene derivative.

When we employ wireless communications in a factory, its channel state can change dynamically due to factory-specific propagation environments. Therefore, it is difficult to realize a stable communication link with common unicast transmissions. In order to realize stable communications in such an environment, in this paper, we focus on broadcast transmissions, where a sender transmits a packet to multiple access points (APs). With broadcast transmissions, even if an AP is not able to receive data because of bad channel conditions, the other APs may receive it, which can contribute to the realization of robust data transmissions. However, link reliability of broadcast transmissions is inherently low due to the absence of ACK and retransmission mechanisms. In order to solve this problem, in this paper, we apply packet-level FEC to broadcast transmissions. With computer simulations and actual indoor experiments, we investigate the effectiveness of broadcast transmissions exploiting multiple AP receptions with packet-level FEC.

Quantum optimal transportation seeks an operator which minimizes the total cost of transporting a quantum state to another state, under some constraints that should be satisfied during transportation. We formulate this issue by extending the Monge-Kantorovich problem, which is a classical optimal transportation theory, and present some applications. As examples, we address quantum walk, quantum automata and quantum games from a viewpoint of optimal transportation. Moreover we explicitly show the folk theorem of the prisoners' dilemma, which claims mutual cooperation can be an equilibrium of the repeated game. A series of examples would show generic and practical advantages of the abstract quantum optimal transportation theory., Comment: 16 pages, 1 figure

l-Ornithine is found in animals as a free amino acid and is a vital component of the urea cycle in the liver; it is reported to have various functions such as promoting wound healing, promoting growth hormone secretion, hypnotic effects, and so on. The present study aimed to investigate the effects of a single oral administration of l-ornithine on 1) the metabolism of amino acids in the liver and skin of mice and 2) the metabolism of polyamines in the skin of mice. To this end, ICR mice were separated into five groups; four groups were administered l-ornithine dissolved in fresh water (3.0 mmol/10 ml/kg) and a fifth group, the control, was not administered l-ornithine. The four groups comprised mice sampled at specific times (30, 60, 120 and 180 min) after oral administration of l-ornithine. We found that metabolism of l-ornithine to l-citrulline was rapid and that l-citrulline concentration remained high in mice sampled at later stages. Similarly, the concentrations of l-proline and glycine, both of which are important components of collagen, also rapidly increased in the skin following l-ornithine treatment. The concentrations of polyamines (putrescine, spermidine and spermine), which are known to increase the synthesis of certain proteins and enhance the epidermal barrier function, were also significantly increased in the skin. Our study shows that oral administration of l-ornithine significantly influences the chemical composition of the skin of mice through increases in both amino acids and polyamines after a short period of time.

To support a human by installing sensor and communication device is widely studied. Human detection is a key technology to trigger such a service. In some cases, the sensor is demanded to be installed into non-electrical object, such as a chair. To make it viable, how electrical power is supplied is problematic. If using commercial electrical power line, the location and mobility of the object are limited. If battery is used, maintenance cost of changing battery arises. Thus, we propose a human detection sensor using electromagnetic noise leaking from commercial power line. This sensor detects a human without electrical power supply, using electromagnetic noise in environment. In past research, basic operation principle is confirmed. However, values of electrical component of the sensor is not explored very well. In this paper, suitable parameters of its CW circuit and antenna are discussed. As a result, it is disclosed that suitable parameter for reverse current of diodes was less than $6 \mu\text{A}$, and capacitance of capacitors was 100 pF. About the size of antenna, the larger output voltage is obtained by the larger size, while the difference of output voltage between presence and non-presence of a human gets smaller. The suitable size of antenna is concluded to be around $30\ \mathbf{cm} \times 40\ \mathbf{cm}$.

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.