This paper is our attempt on the basis of physical theory to bring more clarification on the question ``What is life?'' formulated in the well-known book of Schr\"odinger in 1944. According to Schr\"odinger, the main distinguishing feature of biosystem's functioning is the ability to preserve its order structure or, in the mathematical terms, to prevent increasing of entropy. Since any biosystem is fundamentally open, it is natural to use open system's theory. However, Schr\"odinger's analysis shows that the classical theory is not able to adequately describe the order-stability in a biosystem. Schr\"odinger should also appeal to the ambiguous notion of negative entropy. We suggest to apply the quantum theory. As is well-known, behaviour of the quantum von Neumann entropy crucially differs from behaviour of the classical entropy. We consider a complex biosystem $S$ composed of many subsystems, say proteins, or cells, or neural networks in the brain, i.e., $S=(S_i).$ We study the following problem: if the composed system $S$ can preserve the ``global order'' in the situation of increase of local disorder and if $S$ can preserve its entropy while some of $S_i$ increase their entropies We show that within quantum information theory the answer is positive. The significant role plays entanglement of the subsystems states. In the absence of entanglement, increasing of local disorder generates disorder increasing in the compound system $S$ (as in the classical regime).

It has not been reasonably explained still now, how the “chicken and egg relationship” between gene and protein was formed, although RNA world hypothesis was proposed to aim at explaining formation process of the relationship about 40 years ago. On the other hand, GADV hypothesis advocates that life emerged after five members of the fundamental life system; cell structure, metabolism, tRNA, genetic code and gene, were piled up one by one onto immature [GADV]-proteins, which were produced by random joining of [GADV]-amino acids on the primitive Earth. Furthermore, formation process of the first (GNC)n RNA gene encoding a mature [GADV]-protein can be also reasonably explained according to the hypothesis as follows. Double-stranded (ds)-(GNC)n RNA could be produced by complementary strand synthesis of a single-stranded (ss)-(GNC)n RNA, which was formed by random joining of GNC anticodons carried by four types of AntiC-SL tRNAs. Successively, the first (GNC)n RNA gene was generated upon maturation of an immature [GADV]-protein, which was produced through expression of codon sequence on one strand of ds-(GNC)n RNA, as accumulating necessary base substitutions and raising a weak catalytic activity of the immature protein to a more active state. It is considered that, consequently, a gene encoding a mature protein, which has the “chicken and egg relationship”, was generated for the first time. Therefore, it can be concluded that the “chicken and egg relationship” was built not by formation of either one, gene or protein, but by maturation of an immature gene, which was lead by improvement of catalytic activity of an immature protein. That is, it can be concluded that the reason, why it was unable to give an answer to the question on the formation process of the “chicken-egg relationship” thus far, is because it was an unanswered question.

The steel damper column is an energy-dissipating member that is suitable for reinforced concrete (RC) buildings, and those used for multistory housing in particular. However, the effectiveness of steel damper columns may be affected by the behavior of surrounding members, and this effect can be severe in the case of seismic sequences. This article investigates the nonlinear response of building models having an RC moment-resisting frame (MRF) with and without steel damper columns under seismic sequences. The applicability of the concept of the momentary energy input to the prediction of the peak response of RC MRFs with damper columns under seismic sequences is also investigated. The main findings of the study are summarized as follows. (1) The peak response of RC MRFs with damper columns subjected to sequential accelerations is similar to the peak response obtained considering only the mainshock, whereas the cumulative strain energy of RC MRFs accumulates more for sequential accelerations. (2) The steel damper column is effective in reducing the peak and cumulative responses of RC MRFs in the case of sequential seismic input. (3) The relation of the hysteretic dissipated energy during a half cycle of the structural response and the peak displacement of the first modal response can be properly evaluated using the simple model proposed in this study.

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

We study the effect of the generation of the mechanical transverse wave (MTW)　travelling in the opposite direction (OD) to a moving medium (MM) on the relativistic energy conservation law (RECL). From the viewpoint of the relativity of simultaneity (RS), the time on the coordinate coinciding with the advance end of the wave (AEW) travelling toward the rear of the MM passes faster than that on the coordinate coinciding with the wave source (WS). Then the AEW in the MM travels forward compared to that in the rest frame of reference (RFR) which is stationary relative to the medium when the time on the coordinate coinciding with the WS is same for each inertial frame of reference (IFR). Hence, the coordinate interval (CI) between the AEW and WS in the MM is observed to be larger than that between them in the RFR. We show that this difference holds true for the CI of any portion having transverse velocities mutually converted by the Lorentz transformation (LT). This difference in the CI leads to that in the rest mass (RM). We demonstrate that the RM included in wave motion (WM) in the MM is larger than one included in WM in the RFR when comparing the portions having transverse velocities mutually converted by the LT. This relation holds true for all portions in WM. Therefore, the total coordinate interval of the portion (CIP) and total RM (TRM) included in WM in the MM (WMMM) are large compared to them included in WM in the RFR. Furthermore, we compare the relativistic kinetic energy (RKE) of the MTW travelling in the OD to the MM (ODMM) with that of the MTW propagating in the direction vertical to the moving direction of the medium. We prove that the CIP and RM included in the former MTW are larger than them included in the latter MTW when comparing each portion with the same transverse velocity (TV). Moreover, the total CIP and TRM included in the former MTW are also large compared to them included in the latter MTW. The reason for these is that the latter CIP and RM are equal to them in the RFR when comparing the portions having transverse velocities mutually converted by the LT. On the other hand, the energy supplied to generate each MTW is the same. From these, we demonstrate that the RKE of the MTW travelling in the ODMM can be larger than the total relativistic energy (TRE) of the MTW propagating in the direction vertical to the moving direction of the medium. Consequently, we propose a violation of the RECL and Einstein’s principle of relativity (EPR) because the TRE is not necessarily conserved in the IFR in which the medium is moving.

This article reviews recent innovations in piezoelectric actuators, then indicates the future research targets. In the materials, the piezoelectric performances of relaxor-lead titanate (PZN-PT, PMN-PT) single crystals have been improved significantly by an AC electric poling technique. Also new loss characterization techniques facilitate developing high-power density piezoelectrics. The RMS vibration velocity reaches 0.6 m/s in the k₃₁ mode in lead zirconate titanate (PZT) nowadays, which corresponds to power density 30 W/cm³. Pb-free materials are urged due to the recent political regulation on toxic materials. In device designs, the original multilayer actuators (MLA) with Ag/Pd electrode have been switched to the ones with Cu or pure Ag, in order to suppress the heat generation, then to enhance the device power density. Piezoelectric micro-electro-mechanical-systems (MEMS’s) started to utilize the <1 0 0> oriented epitaxial films of rhombohedral PZT compositions, which exhibits enhanced piezoelectric properties. Also for higher-power applications, aero-sol deposition (AD) methods have been introduced to 10 -thick films. Regarding drive/control techniques in piezo-actuators, three developments are on-going, that is, “negative capacitance” power supplies for driving off-resonance (pseudo-DC) piezo-actuators, capacitive AC power supplies for efficiently driving resonance piezo-actuators, and DC/DC converters for harvesting electric energy from high-impedance piezoelectric devices under noise vibration. The applications of piezoelectric actuators in the 21^st century seem to be oriented toward “politico-engineering” with four keywords, “cooperation, protection, reduction, and continuation”. The sustainability technologies include the following piezoelectric items: (a) Pb-free piezoelectrics, (b) ultrasonic technology for decomposing hazardous materials, (c) reduction of contamination gas, (d) piezoelectric energy harvesting, and (e) device improvement with high energy-efficiency. On the other hand, the following crisis technologies have been developed with piezoelectrics: (a) detection and neutralization technologies of infectious/epidemic diseases such as anthrax, (b) autonomous unmanned underwater, aerial, and land vehicles with piezoelectric actuators, (c) pin-point target weapons, (d) high voltage supplies with piezoelectric transformers, and (e) compact energy sources for remote actuating/sensing systems.

Steel damper columns (SDCs) are energy-dissipating members that are suitable for reinforced concrete (RC) buildings and are often used for multistory housing. The evaluation of the peak deformation and hysteretic dissipated energy of such building structures is essential for the rational seismic design of RC buildings with SDCs. In a previous study, the authors proposed an energy-based prediction procedure for the peak and cumulative response of an RC frame building with SDCs. In this procedure, the accuracy of the equivalent velocity of the maximum momentary input energy (V_ΔE1^*)–peak equivalent displacement (D₁^*_max) relationship is essential for high quality predictions. In this article, the V_ΔE1^*–D₁^*_max relationships of RC moment-resisting frames with and without SDCs are invested using a critical pseudo-double impulse (PDI) analysis based on a study by Takewaki and coauthors. The results show that the V_ΔE1^*–D₁^*_max relationship obtained from the critical PDI analysis agrees well with that calculated from the equations proposed in the previous study.

The response of structures under pulse-like ground motions is characterized by the large amount of energy input in a few cycles. Consequently, structures with insufficient strength may suffer severe damage owing to excessive deformation. In a previous paper, the energy-based prediction procedure for the peak and cumulative response of a reinforced concrete (RC) frame building with steel damper columns was proposed (Fujii and Shioda, 2023). Although this procedure was verified by comparison to the nonlinear time-history analysis (NTHA) results, the performance of the proposed procedure with pulse-like ground motion records has not been verified yet. In this study, the accuracy of the energy-based prediction procedure for an RC frame building with steel damper columns was investigated by considering pulse-like ground motions. The numerical analysis results reveal that the accuracy of the predicted peak response is satisfactory, which agrees with the results of the author’s previous study. However, the accuracy of the predicted total input energy to the building model depends on the ratio of the pulse period of the ground motion to the effective fundamental period of the building model. The reasons for this underestimation of the total input energy are discussed in this paper.

In general, isolators and dampers used in seismically isolated buildings are designed to be isotropic in any horizontal direction. However, in the case of buildings with plan irregularities, their nonlinear responses depend on the direction of seismic loading. To discuss the influence of the angle of seismic incidence (ASI) on the nonlinear response of irregular building structures, it is important to define the angle of the critical axis of the horizontal ground motion. One possible choice is the “principal axis of ground motion” proposed by Arias (1970). However, because this principal axis is independent of the natural period of a structure, it could be complicated to use for seismically isolated structures with long natural periods. In this study, the influence of the ASI of long-period pulse-like seismic input on an irregular base-isolated building is investigated. First, the angle of the principal axis of ground motion is defined in terms of the cumulative energy input. Then, a nonlinear time-history analysis of a five-story irregular base-isolated building is performed using 10 long-period pulse-like ground motion records considering various ASIs. The results show that, compared with the principal axis of ground motion proposed by Arias, defining the principal axis of ground motion in terms of the cumulative energy input is more suitable for discussions concerning the influence of the ASI on the response of an irregular base-isolated building.

Ground-level ozone (O3) increases in the northeastern part of Eurasia, where larch species are dominant trees and have been planted intensively. The Japanese larch (Larix kaempferi; hereafter larch) is classified as the tree species most of its sensitive to O3 based on data from long-shoot needles of seedlings. This criterion should be reconsidered based on O3 uptake, which is strongly depended on stomatal conductance (Gs) of adult trees through the difference in relevant needle traits. Because Gs is closely correlated with photosynthetic activity, we measured the in situ seasonal and yearly change in photosynthetic function, needle mass per area (LMA) and nitrogen (N) content of both short- and long-shoot needles of the canopy of larch trees over successive 3 years. No difference was observed in the in light saturated photosynthetic rate at ambient CO2 (Psat) between needles of hetero types of shoot in the latter part of the growing season, but clear differences were found within a specific year, indicating that seasonal changes in climatic factors determine Psat in the long term. The Psat-N relations differed significantly between the needle types. However, Psat at saturated CO2 (Pmax)-N was quite similar, implying that the CO2 diffusion difference between short- and long-shoots is responsible for the differing Psat -N. In conclusion, seasonal and yearly variations in photosynthetic capacity are mainly determined mainly by climatic variations, whereas shoot type determined the traits of photosynthetic N utilization as well as Gs regulation.

As a matter of course, the first gene must be formed in the absence of gene. On the other hand, many biopolymers including gene are produced under the genetic system in extant organisms. Thus far, no idea explaining how the first gene was formed in the absence of gene, has been proposed except the idea based on the GADV hypothesis. GADV means four amino acids; Gly [G], Ala [A], Asp [D] and Val [V]. In this article, a reliable answer to the question, how the first gene was generated, is provided. The idea is as follows. The first gene (genetic information) was formed by random joining of anticodons, GNCs, which were carried by primeval anticodon stem-loop (AntiC-SL) tRNAs produced during repeated cycles of random joining of nucleotides and degradation of oligonucleotides. However, it might be difficult for many persons to accept the idea, because tRNAs and metabolic pathways using various proteins, which are produced under genetic functions, must be used to form the first gene. Then, it is reconsidered based on definition of genetic information and minimum necessary things to generate the first gene in this article, how the first gene was generated. Consequently, it could be reconfirmed that five prototypes of members (genetic code, tRNA, metabolism, cell structure and protein) composing the fundamental life system, except gene, are certainly necessary to generate the first gene. Namely, it can be concluded that the first gene was formed through nucleotide metabolism with immature [GADV]-proteins, primeval AntiC-SL tRNA formation with immature [GADV]-proteins, formations of single-stranded (GNC)n codon sequence by random joining of anticodons, GNCs, carried by AntiC-SL tRNAs, double-stranded (ds)-(GNC)n RNA and maturation of an immature [GADV]-protein, which was produced from one strand of the ds-RNA. Thus, the first gene was formed using the five primitive or prototypes of members, which were produced in the absence of gene. There would be no other way for generating the first gene.

One of the problems, which make it difficult to solve the mystery of the origin of life, would be how life emerged in chemically complex messy environments on the primitive Earth. It is considered that three main points contributed to open the way to the emergence of life. (1) A characteristic inherent in [GADV]-amino acids, which are easily produced with prebiotic means. (2) Protein 0th-order structure or [GADV]-amino acid composition generating water-soluble globular protein with some flexibility, which can be produced even by random joining of [GADV]-amino acids. (3) Formation of versatile [GADV]-microspheres, which can grow, divide, proliferate even without genetic system, was the emergence of proto-life. (4) [GADV]-microspheres with a higher proliferation ability than others could be selected. The proto-Dawin evolution made it possible to proceed forward to creation of the core life system composed of (GNC)n gene, anticodon stem-loop tRNA or AntiC-SL tRNA (GNC genetic code) and [GADV]-protein. (5) Eventually, the first genuine life with the core life system emerged. Thus, the formation processes of [GADV]-protein and (GNC)n gene in chemically complex messy environments were the steps to the emergence of genuine life.

Proteins having a variety of functions play many essential roles in maintaining various life activities in organisms. Various methods, by which new protein functions can be artificially produced, have progressed rapidly upon development in recombinant DNA technology and effective screening techniques. However, the obtainable scope of the new functions has been restricted in a narrow range, because only functions of presently existing proteins can be used. On the other hand, it has been considered that it would be impossible to create an entirely new protein, which does not show any meaningful homology with any other amino acid sequences of previously existing proteins. The reason is because one amino acid sequence for a protein cannot be selected out from an extraordinary large amino acid sequence diversity as ~10130. As a matter of course, it is impossible to design an amino acid sequence of a protein in advance and a gene encoding the protein cannot be also formed through random process. Nevertheless, extant organisms have generated a variety of entirely new proteins in some way to make full use of them. This means that extant organisms have equipped a mechanism with which entirely new proteins can be produced under the present core life system composed of protein, tRNA (genetic code) and gene. In this article, first I introduce the mechanism, with which entirely new proteins are created in extant organisms, and further propose a novel strategy for application of the mechanism to protein engineering through creation of entirely new proteins, which could contribute to development of various industries.

We study the center of energy (CE) before and after the separation of superposed wave from a moving medium (MM). It is assumed that two out-of-phase mechanical transverse waves propagating from the opposite directions on a medium moving at non-relativistic speeds are superposed and the superposed portion (SP) is separated from the MM at that moment. We consider the CE of the SP before and after the separation from the MM. The location of CE (LCE) of the SP seems to be at the center of it at the moment of superposition. The SP rotates due to the separation from the MM since the velocity of each portion symmetric with respect to the center of the SP is equal in magnitude and opposite in direction. The magnitudes of velocities of the symmetric portions become different as soon as the SP begins to rotate with the separation from the MM. Then the energies of their symmetric portions are not the same, so the LCE of the SP is not at the center of it. As a result, the LCE of it looks different before and after the separation from the MM. We must find a solution to keep the LCE of the SP constant. We propose that two out-of-phase mechanical transverse waves (MTWs) propagating from the opposite directions on a MM originally have hidden difference in relativistic energy and it suddenly appears within the range observable in Newtonian mechanics when the SP starts rotating. This means that the point of view of hidden difference in relativistic energy is necessary to keep the LCE constant.

Understanding the mechanism, how entirely new (EntNew) gene/protein or the first ancestral gene/protein of a family was created, should be one of the most important issues in the biological sciences. However, the mechanism is totally unknown still now. On the other hand, it is well known that mature protein is generally rigid and one catalytic center exists on the protein. Creation of such a mature EntNew gene/protein should be, of course, carried out through random process, because it cannot be designed in advance. However, the EntNew gene/protein never be created by random polymerization of the respective monomeric units, because of the extraordinary large sequence diversities of ~10¹⁸⁰ and ~10¹³⁰, respectively. Protein 0^th-order structure or a specific amino acid composition, in which immature but water-soluble protein can be produced even through random process, holds the key for solving the difficult problem. As it was fragmentally described in the previous papers how and where EntNew gene/protein was created, I describe in detail in this review three processes generating EntNew gene/protein with some flexibility under three genetic codes, the universal genetic code, SNS primitive code and GNC primeval code, and discuss why the mature gene/protein could be created through the processes.

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0^th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

A steel damper column is an energy-dissipating member that is suitable for reinforced concrete (RC) buildings and multistory housing. To assess the seismic performance of buildings with steel damper columns, the peak displacement of the whole building and the energy dissipation demand of the dampers must be evaluated. This article proposes an energy-based prediction procedure for the peak and cumulative response of an RC frame building with steel damper columns. The proposed procedure considers two energy-related seismic intensity parameters, namely the maximum momentary input energy and the total input energy. The peak displacement is predicted considering the energy balance during a half cycle of the structural response, using the maximum momentary input energy. The energy dissipation demand of the dampers is then predicted considering the energy balance during a whole response cycle using the total input energy. The local responses (e.g., peak drift, maximum plastic rotation of beams, maximum shear strain, and energy dissipation demand of dampers) are predicted using pushover analysis. Numerical analysis results for 8- and 16-story RC buildings show that the proposed prediction method achieves satisfactory accuracy.

This paper addresses the issues of how we can quantify structural information for nonparametric distributions and how we can detect its changes. Structural information refers to an index for a global understanding of a data distribution. When we consider the problem of clustering using a parametric model such as a Gaussian mixture model, the number of mixture components (clusters) can be thought of as structural information in the model. However, there does not exist any notion of structural information for nonparametric modeling of data. In this paper we introduce a novel notion of {\em kernel complexity} (KC) as structural information in the nonparametric setting. The key idea of KC is to combine the information bias inspired by the Gini index with the information quantity measured in terms of the normalized maximum likelihood (NML) code length. We empirically show that KC has a property similar to the number of clusters in a parametric model. We further propose a framework for structural change detection with KC in nonparametric distributions. With synthetic and real data sets we empirically demonstrate that our framework enables us to detect structural changes underlying the data and their early warning signals.

Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been elucidated. In the present study, we investigated the role of MDK in pulmonary inflammation experiments using a mouse lipopolysaccharide (LPS)-induced pneumonia model and human bronchial cells. Wild-type and MDK-deficient mice were injected intratracheally with LPS, and several inflammatory parameters were analyzed. In the wild-type mice, mRNA expression of MDK in lung tissues was significantly increased after intratracheal LPS injection. The MDK-deficient mice showed significantly lower counts of total cells and neutrophils, as well as lower concentrations of neutrophil chemokines, KC and MIP-2 in bronchoalveolar lavage fluid, compared to wild-type mice. Moreover, mRNA expressions of TNF-α, KC and MIP-2 in lung tissues, as well as histopathological lung inflammation score, were significantly lower in the MDK-deficient mice. Furthermore, in in vitro experiments using bronchial epithelial cells, LPS stimulation increased mRNA expression of MDK, and MDK knockdown by siRNA decreased LPS-induced TNF-α and CXCL8 upregulation. These findings suggest that deficiency of MDK attenuates LPS-induced pulmonary inflammation.

Steel damper columns (SDCs) are energy-dissipating members that are suitable for reinforced concrete (RC) moment-resisting frames (MRFs) and those often used for multistory housing. In a previous study, an energy-based prediction procedure for the peak and cumulative response of an RC frame building with SDCs was proposed. In this procedure, the accuracy of the equivalent velocity of the maximum momentary input energy (V_ΔE1^*)–peak equivalent displacement (D₁^*_max) relationship is essential for improved prediction. In this article, the seismic capacity curve (V_ΔE1^*–D₁^*_max relationship) of RC MRFs with and without SDCs is evaluated using incremental critical pseudo-multi impulse analysis (ICPMIA). In the ICPMIA, which is based on a study by Takewaki and coauthors, the structure is subjected to various intensities of critical pseudo-multi impulsive lateral force. An ICPMIA of four 8- and 16-story RC MRFs with and without SDCs is performed to obtain their structural behaviors under various intensities of pulsive input. Then, the seismic capacity curve obtained from the ICMPIA results are compared with the predicted results based on the simplified equations. The main findings of this article are as follows. (i) The seismic capacity curve of RC MRFs without SDCs strongly depends on the number of impulsive lateral forces (N_p). As N_p increases, the seismic capacity decreases. The predicted seismic capacity curve severely underestimates that obtained from the ICMPIA in the case of large N_p. This trend is notable when the level of pinching behavior in the RC members is severe. (ii) In the case of an RC MRF with SDCs, however, the influence of N_p on its seismic capacity curve is small. The predicted seismic capacity curve agrees very well with that obtained from the ICMPIA. The influence of the level of pinching behavior in RC members on the seismic capacity curve is small.

In this article, the main building of the former Uto City Hall, which was severely damaged in the 2016 Kumamoto earthquake, is investigated as a case study for the retrofitting of an irregular Reinforced Concrete building using the base-isolation technique. Its peak response is predicted via mode-adaptive bidirectional pushover analysis (MABPA), which was originally proposed by the authors. In the prediction step of MABPA, the peaks of the first and second modal responses are predicted considering the energy balance during a half cycle of the structural response. The numerical analysis results show that the peak relative displacement can be properly predicted by MABPA. The results also show that the performance of the retrofitted building models is satisfactory for the ground motion considered in this study, including the recorded motions in the 2016 Kumamoto earthquake.

Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.

SDG target 12.3 calls for halving food waste at retail, food service, and household by 2030. The food waste index for this purpose includes parts attached to food that are usually removed intentionally ("unavoidable food waste") and allows counting the conversion to animal feed and utilisation as biomaterial as means of reduction. In Japan, the "Food Waste Recycling Law" which has been in effect since 2001, promotes the recycling of food waste generated from businesses, designating feed conversion as top priority. On the other hand, based on the more recent "Food Loss Reduction Promotion Act" of 2019, the government is currently promoting the reduction of avoidable food waste, as to meet the SDG target. Based on statistical sources and interviews with Ministry officers, this paper explains the history and achievements of Japan's 23-year policy based on the Food Recycling Law, as well as the tension between the two legislations.

Studies on the domestication, genetic differentiation, and crop evolution of foxtail millet are re-viewed. Several genetic studies were carried out to elucidate the genetic relationships among foxtail millet accessions originating mainly from Eurasia, based on intraspecific hybrid pollen semi-sterility, isozymes, DNA markers, and single-nucleotide polymorphisms. Most studies suggest that China is the center of diversity of foxtail millet, and landraces were categorized into geographical groups. Furthermore, the evolution of genes was reviewed (i.e., the Waxy gene conferring amylose content in the endosperm, the Si7PPO gene controlling polyphenol oxidase, the HD1 and SiPRR37 genes controlling heading time, the Sh1 and SvLes1 genes involved in grain shattering, and the C gene controlling leaf sheath pigmentation), and the variation and distribu-tion of these genes suggested complex patterns of evolution under human and/or natural selec-tion.

Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

In two-dimensional materials research, oxidation is usually considered as a common source for the degradation of electronic and optoelectronic devices or even device failure. However, in some cases a controlled oxidation can open the possibility to widely tune the band structure of 2D materials. In particular, we demonstrate the controlled oxidation of titanium trisulfide (TiS₃), a layered semiconductor that attracted much attention recently thanks to its quasi-1D electronic and optoelectronic properties and its direct bandgap of 1.1 eV. Heating TiS₃ in air above 300 °C gradually converts it into TiO₂, a semiconductor with a wide bandgap of 3.2 eV with applications in photo-electrochemistry and catalysis. In this work, we investigate the controlled thermal oxidation of individual TiS₃ nanoribbons and its influence on the optoelectronic properties of TiS₃-based photodetectors. We observe a step-wise change in the cut-off wavelength from its pristine value ~1000 nm to 450 nm after subjecting the TiS₃ devices to subsequent thermal treatment cycles. Ab-initio and many-body calculations confirm an increase of the bandgap of titanium oxysulfide (TiO_2-xS_x) when increasing the amount of oxygen and reducing the amount of sulfur.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial blood flow reserve (MFR), and myocardial blood flow volume fraction (MBF), and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 male, 1 female) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86±0.13 vs. 1.08±0.09, p=0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23±0.23 vs. 1.88±0.29, p=0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

The energy yield of the Vehicle-integrated photovoltaic (VIPV) differs from that of the standard photovoltaics (PV). It is mainly by the difference of the solar irradiance onto the car-roof and car-bodies as well as its curved-shape. Both meaningful and practical modeling and measurement of the solar irradiance for VIPV are needed to be newly established, not the extension of the current technologies. The solar irradiance was modeled by a random distribution of the shading objects and car-orientation with the correction of the curved surface of the PV modules. The measurement of the solar irradiance onto the car-roof and car-body was done using five pyranometers in five local axes on the car for one year. The measured dynamic solar irradiance onto the car-body and car-roof was used for validation of the solar irradiance model in the car.

Understanding tumor attachments and management of feeding arteries are very important factors to achieve safe resection of skull base meningioma. We examined the distributions and frequencies of feeding arteries in skull base meningioma by cerebral angiography, and also assessed relationships to tumor attachment for skull base meningioma. We enrolled patients with skull base meningioma who underwent MRI and cerebral digital subtraction angiography (DSA), from September 2015 to October 2022. Subjects comprised 115 patients (32 males, 83 females; mean age, 52.7 years) with 117 meningiomas showing tumor attachments around the “cavernous sinus to upper part of the clivus” (Area 1), “lower part of the clivus to foramen magnum” (Area 2), and “tentorium around the petrous bone” (Area 3). We examined feeding arteries based on cerebral angiography and counted the number of related feeding arteries. Particularly frequent arteries, such as the dorsal meningeal artery (DMA), ascending pharyngeal artery (APA), tentorial artery (TA), and petrosal branch (PB) of the middle meningeal artery (MMA) were analyzed for associations of tumor attachment to Areas 1–3. DMA, APA, TA, and PB are very frequent feeding arteries among skull base meningiomas. In some cases, the artery of the foramen rotundum, posterior ethmoidal artery, recurrent meningeal artery, posterior meningeal artery, etc., supply blood to the skull base meningioma. Meningiomas with DMA as a feeding artery correlated strongly with tumor attachment to Area 1 (p&lt;0.001). Meningiomas with APA correlated strongly with tumor attachment to Area 2 (p&lt;0.001). Meningiomas with TA correlated strongly with tumor attachment to Area 3 (p&lt;0.001). PB correlated with Area 3 (p&lt;0.05). Visualization of these arteries suggests tumor attachments to the correlated areas. An accurate anatomical understanding of tumor attachment and feeding arteries is essential to determine appropriate surgical strategies for skull base meningioma. Pre-operative DSA can provide further understanding of the feeding arteries and attachments of skull base meningioma.

Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but also are candidate drugs for treatment of various diseases, including diabetes and allergy, although no RXR antagonist has yet been approved for clinical use. In this review, we describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

Background The purpose of this study was to clarify the relationship structure of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experience as health-related indicators. Methods Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from anxiety and depression to QOL, and from SOC to anxiety and depression, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences, and from negative experiences to anxiety and depression were considered indirect effects on QOL. Results Goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and indirect effect was 0.163. Conclusions These direct and indirect approaches to difficulties in daily life are very significant because they can provide a basis for development of support strategies to increase QOL.

The health benefits of purple sweetpotato, which is used as an edible food in its natural state and in processed foods and as a natural color pigment, have been recognized. In Japan, sweetpotato has been economically produced in regions below 36°4′N latitude, however, cultivation areas are beginning to expand further north. The anthocyanin and polyphenolics in purple sweetpotatoes cultivated in different locations; I (42°92′ N, 143°04′ E), II (35°99′ N, 140°01′ E), and III (31°72′ N, 131°03′ E), were compared over two years. Total anthocyanin and polyphenolic contents in purple sweetpotatoes tended to be high in location I. Their contents significantly differed over the two years in locations I and III and was dependent on temperature during cultivation. The anthocyanin and polyphenolic compositions differed between locations. The peonidin/cyanidin ratios were higher in location III compared with I and II in all varieties. The relative amount of chlorogenic acid was higher in location I, while the amount of 3,4- and 4,5-dicaffeoyolquinic acids were higher in location III, suggesting that the variability of the anthocyanin and polyphenolic content and composition was dependent on cultivation conditions. This study suggested that northern areas in Japan are an alternative production area and may yield higher amounts of anthocyanin and polyphenolics.

The copolyester of 3-hydroxybutyrate (3HB) and 3-hydoxyhexanoate (3HHx), PHBHHx, is a bi-odegradable plastic that has a high flexibility, softness, wide process window and marine bio-degradability. PHBHHx is usually produced from structurally related carbon sources such as vegetable oils or fatty acids but not from inexpensive carbon sources like sugars. In the previous studies, we demonstrated that engineered strains of hydrogen-oxidizing bacterium, Cupriavidus necator synthesized PHBHHx with high cellular content from not only sugars but also from CO2 as the sole carbon source in the flask culture. In this study, highly efficient production of PHBHHx from CO2 was investigated by pH-stat jar cultivation of the recombinant C. necator strains with feeding the substrate gas mixture (H2/O2/CO2=8:1:1) to complete mineral medium in recycled-gas closed-circuit culture system. As the result with the strain MF01/pBPP-ccrMeJAc-emd, the dry cell mass and PHBHHx concentration reached up to 59.62 ± 3.18 g･L-1 and 49.31 ± 3.14 g･L-1, respectively after 212 h of jar cultivation with limited addition of ammonia and phosphate solutions. The 3HHx composition was close to 10 mol% which is suitable for practical applica-tions. It is expected that autotrophic cultivation of the recombinant C. necator can be a feasible process for mass production of PHBHHx from CO2.

Target 12.3 of the United Nations Sustainable Development Goals (SDGs) calls for halving per capita global food waste at the retail and consumer levels, by 2030. The Food Waste Index is suggested as a methodology for grasping the situation. This paper focuses on the consumer level (household food waste). We argue that in order for generating useful information for devising and implementing effective measures for reducing food waste, it should be measured at Level 3 of the Food Waste Index, based on sorting analysis of generated waste, making a distinction between avoidable and non-avoidable food waste. Furthermore, a breakdown by sub-categories that reflect the flow of food in the household could help identify target behaviours. We have developed a categorisation scheme that is internationally agreeable and adoptable, and 1) generates useful information for policy-making and for tackling with reduction of food waste, 2) makes clear the concept of avoidable food waste, and 3) is practical and does not overcomplicate the work of grasping the situation of food wastage. Results of workshops regarding this scheme suggest that the scheme satisfies the criteria. This scheme has been applied to a few sorting analyses of household food waste in Japan, and their results are compared.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

Toxic advanced glycation end-products (TAGE), formed by glyceraldehyde (GA) as an intermediate in the non-enzymatic reaction with intracellular proteins, are highly cytotoxic and have been implicated in the pathogenesis of various diseases. However, the mechanisms underlying the degradation and removal of TAGE remain largely unknown. In the present study, we identified the checkpoint kinase-1 (CHK1) mutant, d270KD, which was rapidly degraded intracellularly by GA, and showed that its degradation was mainly mediated by the ubiquitin-proteasome pathway. The high-molecular-weight complexes formed by the GA stimulation of d270KD were abundant in the RIPA-insoluble fraction, which also contained high levels of TAGE. The knockdown of p62/SQSTM1 reduced the amount of high-molecular-weight complexes in the RIPA-insoluble fraction, indicating its involvement in the formation of TAGE aggregates. The present results suggest that the ubiquitin-proteasome pathway and p62 play a role in the degradation and aggregation of intracellular TAGE formed by GA. This study provides new insights into the mechanisms underlying TAGE metabolism and may lead to the development of novel therapeutic strategies for diseases associated with TAGE accumulation.

A car-roof photovoltaic has an enormous potential to change our society. With this technology, 70% of the personal car can run by the solar energy collected by the solar panel on its car-roof. Unfortunately, it is not a simple extension of the conventional photovoltaic technology. This paper list what we need to do for realizing the future that majority of the personal cars run by renewable solar energy, after clarification of the difference from the conventional photovoltaic technology. In addition to the technological development, the standardization of this innovative technology will be important, and the list was made highlighting the standardization.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin T and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, it may take several hours to reach diagnostic values for ACS. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin T and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group consisted of 24 healthy volunteers were analyzed using liquid chromatography-time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00-1.00). In contrast, those for troponin T and CK-MB were 0.917 (95% confidence interval [CI]: 0.812-1.00) and 0.988 (95% CI: 0.966-1.00), respectively. This study showed the potential of combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than that of troponin T and CK-MB.

Nanostructured transition metal nitrides (TMNs) have been considered a promising substitute for precious metal catalysts toward ORR due to their multi-electron orbitals, metallic properties, and low cost. To design TMNs catalysts with high catalytic activity toward ORR, the intrinsic features of the influencing factor on the catalytic activity toward ORR of nanostructured TMNs need to be investigated. In the paper, titanium nitride (TiN), zirconium nitride (ZrN), and hafnium nitride (HfN) nanoparticles (NPs) are high-efficiency and one-step synthesized by the direct current arc plasma. TiN, ZrN, and HfN NPs with an oxidation layer are applied as the catalysts of hybrid sodium-air batteries (HSABs). The effect of composition and structure attributes of TMNs on ORR catalysis is defined as follows. (ⅰ) Composition effect. With the increase of the oxygen content, the catalytic ORR capability of TMNs decreases progressively due to the reduction of oxygen adsorption capacity; (ⅱ) Structure effect. The redistribution of the density of states (DOS) of ZrN indicates higher ORR activity than TiN and HfN. HSABs with ZrN exhibit an excellent cyclic stability up to 137 cycles (about 140 h), an outstanding rate performance, and a specific capacity of 2817 mAh·g−1 at 1.0 mA·cm−2.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer has a high risk of aggravation and mortality than in healthy infected individuals. The inoculation with the COVID-19 vaccine reduces the risk of SARS-CoV-2 infection and COVID- 19 severity. However, vaccination-induced production of anti-SARS-CoV-2 antibodies is said to be lower in patients with cancer than in healthy individuals. Additionally, the rationale for why patients with cancer become more severe with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in primary tumor and micrometastasis tissues of patients with cancer and COVID-19. In this study, angiotensin-converting enzyme 2 (ACE2) expression was observed, and SARS-CoV-2 particles were detected in ovarian tissue cells in contact with the micrometastatic niche of high-grade serous ovarian cancer. We believe that more severe COVID-19 cases in patients with cancer may be attributed to these pathological features.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Aedes aegypti is inherently susceptible to arboviruses. The geographical expansion of this vector host species has led to the persistence of Dengue, Zika and Chikungunya human infections. These viruses take advantage of the mosquito’s cell to create an environment conducive for their growth. Arboviral infection triggers transcriptomic and protein dysregulation in Ae. aegypti and in effect, host antiviral mechanisms are compromised. Currently, there are no existing vaccines able to protect human hosts from these infections and thus, vector control strategies such as Wolbachia mass release program is regarded as a viable option. Considerable evidence demonstrates how the presence of Wolbachia interferes with arboviruses by decreasing cellular components vital for the pathogen and strengthening antiviral host responses. However, variation in the magnitude of Wolbachia’s viral inhibition that is neither due to strain nor density has been observed. Furthermore, the cellular mechanisms involved in the endosymbiont’s pathogen-blocking differs among hosts. This prompts the need to explore the cellular interactions between Ae. aegypti-arboviruses-Wolbachia and how these interactions overall affect the mosquito’s cell. Understanding what happens at the cellular and molecular level will provide evidence on the sustainability of Wolbachia vector control.

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolyte and acid base, and is associated with poor prognosis and prolonged hospitalization. Therefore, early diagnosis and treatment to avoid the severe AKI stage is important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

The contactless coalescence of a droplet is of paramount importance for physical and industrial applications. This paper describes a coalescence method in mid-air via acoustic levitation using an ultrasonic phased array system. Acoustic levitation using ultrasonic phased arrays provides promising lab-on-a-drop applications, such as transportation, coalescence, mixing, separation, evaporation, and extraction in a continuous operation. The mechanism of droplet coalescence in mid-air may be better understood by experimentally and numerically exploring the droplet dynamics immediately before the coalescence. In this study, water droplets were experimentally levitated, transported, and coalesced by controlling acoustic fields. We observed that the edge of droplets deformed and attracted each other immediately before the coalescence. Through image processing, the radii of curvature of the droplets were quantified and the pressure difference between the inside and outside the droplet was simulated to obtain the pressure and velocity information on the droplet surface. The results revealed that the sound pressure acting on the droplet clearly decreased before the impact of the droplets. This pressure on the droplets was quantitatively analyzed from the experimental data. Our experimental and numerical results provide deeper physical insights into contactless droplet manipulation for futuristic lab-on-a-drop applications.

A tabletop system can facilitate multi-user collaboration in a variety of settings including small meetings, group work, and education and training exercises. The ability of identifying the users touching the table and their positions can promote collaborative work among participants, so methods have been studied that involve the attaching of sensors to the table or chairs or to the users themselves. An effective method of recognizing user actions without placing a burden on the user would be some type of visual process, so the development of a method that processes multi-touch gestures by visual means is desired. This paper describes the development of a multi-touch tabletop system using infrared image recognition for user position identification and presents the results of touch-gesture recognition experiments and a system usability evaluation. Using an FTIR touch panel and infrared light, this system picks up the shadow area of the user’s hand by infrared camera in relation to user touch operations and estimates user position by image recognition. The multi-touch gestures prepared for this system include an operation to change the direction of an object to face the user and a copy operation in which two users generate duplicates of an object. The average recognition rate of the change-direction gesture and copy gesture were found to be 96% and 85%, respectively. In addition, the system usability evaluation revealed that prior learning was easy and that system operations could be easily performed.

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigro-striatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. Synthesis of human NM is regarded to be similar to that of melanin in melanocytes; Melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then synthesized to NM. Intracellular NM accumulation above a specific threshold was reported to be associated to DA neuron death and PD phenotypes. This review reports recent progress in biosynthesis and pathophysiology of NM in PD.

Multichannel EEGs were obtained from healthy participants in the eyes-closed no-task condition (where the alpha component is typically abolished). EEG dynamics in the two conditions were quantified with two related binary Lempel-Ziv measures of the first principal component and with three measures of integrated information including the more recently proposed integrated synergy. Both integrated information and integrated synergy with model order p=1 had greater values in the eyes closed condition. If the model order of integrated synergy was determined with the Bayesian Information Criterion, this pattern was reversed, and in common with other measures, integrated synergy was greater in the eyes open condition. Eyes open versus eyes closed separation was quantified by calculation of the between-condition effect size. Lempel-Ziv complexity of the first principal component showed greater separation than the measures of integrated information. The performance of the integrated information measures investigated here when distinguishing between indisputably different physiological states encourages caution when advocating for their use as measures of consciousness.

In this paper, a novel pendulum-type accelerometer based on hetero-core fiber optics has been proposed for structural health monitoring targeting large-scale civil infrastructures. Vibration measurement is a non-destructive method for diagnosing the failure of structures by assessing natural frequencies and other vibration patterns. The hetero-core fiber optic sensor utilized in the proposed accelerometer can serve as a displacement sensor with robustness to temperature changes in addition to immunity to electromagnetic interference and chemical corrosions. Thus the hetero-core sensor inside the accelerometer measures applied acceleration by detecting the rotation of an internal pendulum. A series of experiments showed that the hetero-core fiber sensor linearly responded to the rotation angle of the pendulum ranging within ±5°, and furthermore the proposed accelerometer could reproduce the waveform of input vibration in a frequency band of several Hz order.

Under inflammatory conditions including lymphatic disorders, bone marrow-derived myeloid cells often express lymphatic endothelial cell (LEC) markers called LEC progenitor cells, which extend lymphatic vessels by fusing with existing lymphatic vessels. However, studies on the mechanism of lymphatic regeneration using three-dimensional images of lymphatic structures are limited. In this study, scanning electron microscopy (SEM) was used to observe the three-dimensional structure of lymphangiogenesis in a mouse model of secondary lymphedema. The model was established in C57BL/6J mice via circumferential incision in the inguinal region of the left hind limb. Skin samples were obtained from the lymphedema region on days 2, 5, and 8 after surgery. To determine lymphatic vessel positions using SEM analysis, we detected anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity in serial sections and overlaid them during SEM observation. On days 2 and 5, spherical cells, probably myeloid cells, were attached and fused to the LYVE-1-positive lymphatic vessel walls. On day 8, spherical cells were converted to string-shaped cells, forming a new lymphatic vessel wall resembling an intraluminal pillar. Our results show the three-dimensional lymphatic structures formed during lymphatic regeneration.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, QOL survey is difficult using patients. We created cancer scenarios and investigated QOL utility values among the general public using vignette-based methods. On the other hand, some scenarios may have been difficult for the general public to image and understand. Therefore, we conducted a QOL survey among physicians. This survey was conducted by interviewing physicians adminis-tering chemotherapy to patients for recurrent/metastatic pancreatic cancer. Responses were eval-uated using Composite Time Trade-Off (cTTO) and Visual Analog Scale (VAS) for 11 pancreatic cancer status scenarios to be evaluated (survey scenarios). Survey scenarios consisted of health state, type and Grade of adverse events. Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). Twenty responders answered in this survey, however two responses were excluded because of inconsistent responses. The stable disease had the highest QOL value for both assessment method. Whereas progression disease (PD) had the lowest QOL value. The physicians scored higher QOL values on VAS and cTTO than the general public in all survey scenarios. The QOL values obtained by physicians were consistent with the degree of sta-tus in any assessment scenarios.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.

It is difficult to obtain necessary information accurately from Social Networking Service (SNS) while raising children, and it is thought that there is a certain demand for the development of a system that presents appropriate information to users according to the child's developmental stage. There are still few examples of research on knowledge extraction that focuses on childcare. This research aims to develop a system that extracts and presents useful knowledge for people who are actually raising children, using texts about childcare posted on Twitter. In many systems numbers in text data are just strings like words and are normalized to zero or simply ignored. In this paper, we created a set of tweet texts and a set of profiles created according to the developmental stages of infants from "0-year-old child" to "6-year-old child". For each set, we used ML algorithms such as NB (Naive Bayes), LR (Logistic Regression), ANN (Approximate Nearest Neighbor algorithms search), XGboost, RF (random forest), decision trees, and SVM (Support Vector Machine) to compare with BERT, a neural language model, to construct a classification model that predicts numbers from "0" to "6" from sentences. The accuracy rate predicted by the BERT (Bidirectional Encoder Representations from Transformers) classifier was slightly higher than that of the NB, LR, ANN, XGboost, RF, decision trees, and SVM classifiers, indicating that the BERT classification method was better.

It is difficult to obtain necessary information accurately from Social Networking Service (SNS) while raising children, and it is thought that there is a certain demand for the development of a system that presents appropriate information to users according to the child's developmental stage. There are still few examples of research on knowledge extraction that focuses on childcare. This research aims to develop a system that extracts and presents useful knowledge for people who are actually raising children, using texts about childcare posted on Twitter. In many systems numbers in text data are just strings like words and are normalized to zero or simply ignored. In this paper, we created a set of tweet texts and a set of profiles created according to the developmental stages of infants from "0-year-old child" to "6-year-old child". For each set, we used Support Vector Machine (SVM), and Bidirectional Encoder Representations from Transformers (BERT), a neural language model, to construct a classification model that predicts numbers from "0" to "6" from sentences. The accuracy rate predicted by the BERT classifier was slightly higher than that of the SVM classifier, indicating that the BERT classification method was better.

Coronavirus disease 2019 (COVID-19) affected not only individuals but also families. The purpose of this study was to clarify the temporal changes in the impact of the COVID-19 pandemic on entire families with older adults susceptible to infection living on small islands in Japan over the duration of the pandemic. Family ethnographic research was conducted from 2021 to 2023, using the Concentric Sphere Family Environment Theory as the theoretical framework. Formal interviews were conducted with 20 families. In addition, data from informal interviews, participant observation and other sources were compiled into field notes. All data on the impact on the entire family were extracted and content analysis was conducted. Five categories and a total of 85 subcategories were extracted. The results show that COVID-19 exerted not only negative but also positive impacts on the entire family, and their temporal changes are clarified. The impact on families is believed to have been influenced by the family external environment, such as increases and decreases of infection cases or events that occurred outside the family. The knowledge acquired from these studies will help healthcare professionals in providing appropriate family support.

Impact load was applied to hardened cement paste (HCP) specimens using a gas gun to investigate microscopic changes in the specimens and develop a better response model of concrete subjected to impact load. Plasma emission was observed at the moment of impact at 420 m/s and the colour of the portion near the impact point turned brighter. This brighter portion was analysed, and it was observed that the pore structure was coarser compared to the other portion; however, the results of thermogravimetry and X-ray diffraction analysis were similar. A possible reason is that the generated heat was instantaneous and the rate of the temperature increase in the HCP decreased due to evaporation of water in the HCP. These results indicate that during impact at a few hundred m/s, porosity increase due to heat effect is more dominant than porosity decrease due to mechanical compaction.

Among the five human senses, light, sound, and force perceived by eye, ear, and skin, respectively are physical actions, and therefore can be easily measured and expressed as objective, univocal, and simple digital data with physical quantity. However, taste and odor molecules perceived by tongue and nose are chemical actions, it has been difficult to express them as objective and univocal digital data, since no reference chemicals can be defined. Therefore, while the recording, saving, transmitting to remote locations, and replaying human visual, auditory, and tactile information as digital data in digital devices has been realized (this series of data flow is defined as DX (digital transformation) in this review), the DX of human taste and odor information is not yet in the realization stage. Particularly, since there are at least 400,000 types of odor molecules and an infinite number of complex odors that are mixtures of these molecules, it has been considered extremely difficult to realize "human olfactory DX" by converting all odors perceived by the human olfaction into digital data. In this review, we discuss the current status and future prospects of the development of "human olfactory DX," which we believe can be realized by utilizing odor sensors that employ the olfactory receptors (ORs) that support human olfaction as sensing molecules (i.e., human OR sensor).

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the characterization of the protein-protein interactions of the vPIC factors has not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral factors has not been sufficiently revealed. Here, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Gln36, His41 and Trp170) on ORF18 that were responsible for its interaction with ORF30. The artificial intelligence (AI) system AlphaFold2 predicted that identified four residues are exposed to the surface of ORF18 and located in proximity to each other in the surface of ORF18. Thus, AI-predicted model supports the importance of four residues for binding of ORF18 to ORF30. Our results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions.

Recent studies have indicated that terahertz time-domain spectroscopy (THz-TDS) can stably and efficiently acquire output spectra using an affordable and compact multimode laser diode (MMLD) with delayed optical feedback as the light source. This research focused on a numerical analysis of the optimal conditions for employing an MMLD with delayed optical feedback (chaotic oscillating laser diode) in THz-TDS, utilizing multimode rate equations. The findings revealed that the intermittent chaotic output generated by the MMLD, characterized by concurrent picosecond pulse oscillations lasting several tens of picoseconds, proves to be highly effective for THz-TDS. By appropriately setting the amounts of injection current and optical feedback, and the delay time of optical feedback, intermittent chaotic oscillation can be attained within a considerably broad parameter range. Moreover, both the MMLD output spectrum and the THz-TDS output spectrum exhibit a consistently stable shape at the microsecond scale, demonstrating the attractor properties inherent in an MMLD with delayed optical feedback.

Predictive simulation of concurrent debris flow using only pre-disaster information has proven to be difficult as a result of problems in predicting the location of debris-flow initiation (i.e., slope failure). However, because catchment topography has concave characteristics, with all channels in a catchment joining each other as they flow downstream, it is possible to predict damage to downstream area using relatively inaccurate initiation points. Based on this, this paper presents methodologies employing debris-flow initiation points generated randomly using statistical slope failure prediction. A many-case simulation across numerous initiation points was performed to quantify the effect of slope-failure location in terms of deviations in the predicted water level and terrain deformation. It was found that the relative standard deviation diminished as the points approached the downstream area, indicating a location-based predictability effect.

Direct electron transfer (DET)-type bioelectrocatalysis, which couples electrode reactions and catalytic functions of redox enzymes without any redox mediator, is one of the most intriguing subjects studied over the past decades in the field of bioelectrochemistry. In order to realize the DET-type bioelectrocatalysis and to improve the performance, nanostructures of the electrode surface have to be carefully tuned for each enzyme. In addition, enzymes can also be tuned by protein engineering approach for the DET-type reaction. This review summarizes the resent progresses in this field of the research, while taking into consideration of the importance of nanostructure of electrodes as well as redox enzymes. Described are basic concepts and theoretical aspects of DET-type bioelectrocatalysis, significance of nanostructures as scaffolds for DET-type reactions, protein engineering approached for DET-type reactions, and concepts and facts of bidirectional DET-type reactions, from a cross-disciplinary viewpoint.

Bioelectrocatalysis has become one of important research fields in electrochemistry and provided a firm base for an important technology for application to various bioelectrochemical devices such as biosensors, biofuel cells, and biosupercapacitors. The understanding and technology in bioelectrocatalysis have been greatly improved by introducing nanostructured electrode materials and protein-engineering methods over the last few decades. Recently, the electro-enzymatic production of renewable energy resources and useful organic compounds (bioelectrosynthesis) also attracts worldwide attention. In this review, we summarize recent progress in applications of enzymatic bioelectrocatalysis.

Bioelectrocatalysis provides the intrinsic catalytic-functions of redox enzymes to non-specific electrode reactions and is the most important and basic concept for biosensors. This review starts by describing fundamental characteristics of bioelectrocatalytic reactions in mediated and direct electron transfer types from a theoretical viewpoint and summarizes amperometric biosensors based on multi-enzymatic cascades and for multi-analyte detection. The review also introduces prospective aspects of two new concepts of biosensors: mass-transfer-controlled (pseudo)steady-state amperometry at microelectrodes with enhanced enzymatic activity without calibration curves and potentiometric coulometry at enzyme/mediator-immobilized biosensors for absolute determination.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disorder most commonly caused by mutations disrupting the reading frame of the dystrophin (DMD) gene. DMD codes for dystrophin, which is critical for maintaining the integrity of muscle cell membranes. Without dystrophin, muscle cells receive heightened mechanical stress, becoming more susceptible to damage. An active body of research continues to explore therapeutic treatments for DMD as well as to further our understanding of the disease. These efforts rely on having reliable animal models that accurately recapitulate disease presentation in humans. While current animal models of DMD have served this purpose quite well, each comes with their own limitations. To help overcome this, clustered regularly interspaced short palindromic repeats (CRISPR)-based technology has been extremely useful in creating novel animal models for DMD. This review focuses on animal models developed for DMD that have been created using CRISPR, their advantages and disadvantages as well as their applications in the DMD field.

The relationship between city size, coastal land use and air temperature rise with distance from coast during summer day is analyzed using the meso-scale Weather Research & Forecasting (WRF) model in five coastal cities in Japan with different sizes and coastal land use (Tokyo, Osaka, Nagoya, Hiroshima and Sendai) and inland cities in Germany (Berlin, Essen and Karlsruhe). Air temperature increased as distance from the coast increased, reached its maximum, and then decreased slightly. In Nagoya and Sendai, the number of urban land use in coastal areas is less than the other three cities, where air temperature is a little lower. As a result, air temperature difference between coastal and inland urban area is small and the curve of air temperature rise is smaller than those in Tokyo and Osaka. In Sendai, air temperature in the inland urban area is the same as in the other cities, but air temperature in the coastal urban area is a little lower than the other cities, due to about one degree lower sea surface temperature influenced by the latitude. In three German cities, the urban boundary layer may not develop sufficiently because the fetch distance is not enough.

The outdoor field test of the 4-terminal on Si tandem photovoltaic module (specifically, InGaP/GaAs on Si) was investigated and performance model, considering spectrum change affected by fluctuation of atmospheric parameters, was developed and validated. The 4-terminal on Si tandem photovoltaic module had about 40 % advantage in seasonal performance loss compared with standard InGaP/GaAs/InGaAs 2-terminal tandem photovoltaic module. This advantage is expanded in (subarctic zone) < (temperate zone) < (subtropical zone). The developed and validated model used all-climate spectrum model and considered fluctuation of atmospheric parameters, and can be applied every type of on-Si tandem solar cells.

As digitalization expands across all sectors, the economic toll of software defects on the U.S. economy reaches up to $2.41 trillion annually. High-profile incidents like the Boeing 787-Max 8 crash have shown the devastating potential of these defects, highlighting the critical importance of software testing within quality assurance frameworks. However, due to its complexity and resource intensity, the exhaustive nature of comprehensive testing often surpasses budget constraints. This research utilizes a machine learning (ML) model to enhance software testing decisions by pinpointing areas most susceptible to defects and optimizing scarce resource allocation. Previous studies have shown promising results using cost-sensitive training to refine ML models, improving predictive accuracy by reducing false negatives through addressing class imbalances in defect prediction datasets. This approach facilitates more targeted and effective testing efforts. Nevertheless, the generalizability of these models across different projects (cross-project) and programming languages (cross-language) remained untested. This study validates the model's applicability across diverse development environments by integrating various datasets from distinct projects into a unified, using a more interpretable ML approach. The results demonstrate that ML can support software testing decisions, enabling teams to identify up to seven times more defective modules with the same testing effort as a benchmark.

The digital era has significantly amplified the volume of online reviews, presenting both opportunities and challenges in harnessing insights from consumer feedback. Aspect-Based Sentiment Analysis (ABSA) has emerged as a crucial tool for distilling sentiments from these reviews, providing valuable data for enhancing product and service quality. This study introduces an advanced hybrid model, AdvSentiNet, which integrates adversarial training into the state-of-the-art framework to elevate the precision of sentiment detection at the aspect level. By employing an adversarial network, where a generative model competes against a classifier by crafting highly realistic synthetic samples, we aim to bolster the model's resilience against varied data samples. This innovative approach, unexplored in its entirety within the realm of ABSA, demonstrated remarkable performance improvements on benchmark datasets. For instance, accuracy on the SemEval 2015 dataset escalated from 81.7% to 82.5%, and for the SemEval 2016 dataset, it surged from 84.4% to 87.3%.

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. IL-1β also leads to osteoarthritis through NF-ĸB, IκBζ, and Zn²⁺-ZIP8-MTF1 axis. IL-1, IL-6, and TNFα play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as BMP, FGF, PTHrP, and Indian hedgehog, play roles regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling cause genetic disorders in cartilage and skeletal tissues. FOP, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. mTOR inhibitors were found to prevent ectopic ossification by ACVR1 mutations. ACH and related diseases are autosomal genetic diseases, which manifest severe dwarfism. CNP is currently the most promising therapy for ACH. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels sheds light on the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Cervical mesonephric ductal adenocarcinoma (MA) is a HPV-independent adenocarcinoma that originates from remnants of the wolffian duct in the male reproductive system during fetal development and occurs in middle-aged women. MA is a rare disease that accounts for less than 1% of all cervical adenocarcinomas. We report a case of MA in which abdominal radical hysterectomy(ARH) was performed after neoadjuvant chemotherapy (NAC). The patient was a 66-year-old woman with abnormal genital bleeding. A colposcopy examination revealed macroscopic invasive cancer. A pelvic MRI scan revealed a 53 × 26 mm tumor in the cervix, and the histological diagnosis of the cervix was endometrioid carcinoma, with the diagnosis being cervical adenocarcinoma cT1b3N0M0. One course of NAC with paclitaxel-carboplatin (PC) was administered to shrink the tumor and stop the bleeding, and ARH was performed. Postoperative histopathological diagnosis was MA. The surgical margins of the resected specimen were negative, and NAC had been effective, so the patient underwent five courses of PC therapy after surgery. There has been no recurrence 12 months after surgery. There is no established standard treatment, but there are reports that PC therapy is effective. It is necessary to search for effective treatments by following up and accumulating further cases.

Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a life-long asymptomatic balance between infected cells and host antiviral immunity, but 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides also promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of viral pathogenicity. As CD4+ T cells play a central role in host immunity, deregulation of their function and differentiation by HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs immunological conditions. Various therapeutic approaches have been developed to treat these abnormalities. Allogeneic hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL; however, the patient's immune state may also contribute to its outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, also depends on immune functions, such as antibody-dependent cytotoxicity. In this review, we comprehensively summarize the immunological pathogenesis of HTLV-1 infection in ATL and integrate clinical findings to determine the factors to be considered for developing treatment strategies for ATL.

The effect of retrogression re-aging treatment (RRA) on corrosion behavior of 7055 Al-Zn-Mg alloy were studied. Results provides the corrosion resistance could be greatly improved by RRA. After the RRA treatment, the isolated precipitates occurred on grain boundaries (GBs) and the low angle grain boundaries (LAGBs) presented a larger fraction compared to the single-stage peaking aging. The samples after RRA treatment also show better corrosion resistance than the single-stage peak aging. The results of electrochemical impedance spectroscopy (EIS) show that impedance spectrum is consisted of semi-infinite layer diffusion impedance and stagnant Weber impedance. The semi-infinite layer diffusion impedance corresponded a limited retention layer on the electrode surface. In corrosion process, Weber impedance corresponded to stagnant layer of corrosion products generated by the anode branches. The RRA sample has the high Rf and low Cf, Cp values, and the corrosion current density of the RRA samples is ten times less than the single-stage peak aging samples with the 10% hardness losing.

Two-stage surgery is unintentionally necessary when total tumor removal cannot be accomplished in the first surgery, although, it has not yet been established how to leave the tumor for the next surgery. There is a risk of postoperative hemorrhage in the residual tumor, especially in hypervascular tumors. We report a case of hypervascular choroid plexus papilloma in which preservation of intratumoral venous drainage was considered important to avoid hemorrhagic complications during a two-stage surgery. In hypervascular tumor resection, to prevent postoperative hemorrhage associated with a residual tumor, it may be important to preserve venous drainage of the tumor.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by the extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

We investigated humoral immune responses in 222 unvaccinated Japanese people after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2021. Anti-spike protein IgG antibody levels and neutralizing antibody titers were measured in serum samples obtained within 20–180 days after diagnosis. The geometric mean of antibody titers was 1555 ELU/mL (95% confidence interval [CI] = 1257-1923), and the neutralizing activities (50% inhibitory dilution) was 253 (95% CI = 204-313). The antibody titer and neutralizing activity both increased with increasing disease severity, and both values were approximately 4-fold higher for hospitalized patients than for non-hospitalized patients. However, these differences were smaller in older patients. The humoral immune response, which increased with increasing disease severity, gradually decreased over time after SARS-CoV-2 infection. Most patients with mild or moderate symptoms sustained neutralizing activity for up to 180 days after the infection, the decay of the neutralizing activity in the patients with asymptomatic was rather faster than other groups. 11.7% (26/222) of patients had very low neutralizing activity, and half of these were in the age of 20s. Our study results show the importance of measuring the neutralizing activity to confirm the immune status and also estimate the timing of vaccine.

We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.

Mangrove creeks adjoining typical riverine mangrove forests is known to be a net source of CO2 and dissolved inorganic carbon (DIC) to the ocean due to the decomposition of rich organic carbon in the soil; such information is limited in fringe mangroves. This study aims to clarify the difference in carbonate processes between the two types of mangrove forests. We conducted continuous monitoring of the partial pressure of carbon dioxide (pCO2) and measured carbonate chemistry parameters (total alkalinity (TA) and DIC) in two types of mangrove areas located in Okinawa, Japan. The result showed that the maximum pCO2 reached 5242 µatm in the Fukido River estuary (a riverine mangrove), whereas it was only 765 µatm on the Yubu coast (a fringe mangrove). The measured maximum TA and DIC values were 3285 µM and 3283 µM in the Fukido River estuary and 3162 µM and 2977 µM on the Yubu coast. These indicate that pCO2 on the Yubu coast was maintained at low values by the carbonate buffering capacity even when TA and DIC increased rapidly. The mangroves on the Yubu coast grow on dead corals and coral soils. It was suggested that the DIC/TA ratio was constantly kept at approximately 0.9 due to TA production by the dissolution of calcium carbonate (CaCO3), which resulted in lower pCO2.

This paper deals with the possibility for construction of the database on friction coefficient on the actual roads from the viewpoint of traffic safety. A measurement algorithm is determined in order to construct road friction measuring device. Next, the tires used for measurement are selected and the characteristics are measured using bench tire characteristic tester, and the measuring device is designed and constructed based on the characteristics. Finally, using this device, the measurement results of the road friction characteristics for two types of road surfaces are shown.

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for &gt;14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al [7], and treatment efficacy was evaluated using the Visual Analogue Scale, wherein patients gave subjective ratings for their symptoms (reductions by &gt;50% after administration of EL for 4 weeks were defined as mprovements). Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55% and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases of sleepiness and one case of dizziness). We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

In 2021, Japan's medical expenses will exceed 45 trillion yen, and the shortage of doctors, especially in remote and mountainous areas, is becoming serious, making it difficult to maintain the medical system. We have conducted a study of 800 health consultation text data. We developed an on-premise health counseling LLM system by constructing a dialogue flow based on 800 health counseling text data. We conducted a Turing test of this system using 200 test data and verified its effectiveness with three medical professionals. The Turing test was a comparison experiment between this system and a conventional LLM system. The health counseling LLM infrastructure focuses on exercise guidance and analyzes gender, height, weight, body fat percentage, and muscle mass. While the accuracy of the conventional LLM system was 87.5%, this system showed a higher accuracy of 93.1%. Although telemedicine has been slow to spread in Japan, the introduction of a health consultation system using Personal Health Record and Large Language Models has the potential to reduce the burden on physicians. In the future, we aim to improve the accuracy of the system by using Japanese language and medical-specific evaluation scales.

This research program investigated the effects of layer thickness (50 and 100 microns) on the microstructure and mechanical properties of electron beam powder bed fusion (EBPBF) additive manufacturing of Inconel 625 alloy. The as-built 50 and 100 micron layer thickness components were also heat treated at temperatures above 1100 oC, which produced a recrystallized grain structure containing annealing twins in the 50 micron layer thickness components, and a duplex grain structure consisting of islands of very small equiaxed grains dispersed in a recrystallized, large-grain structure containing annealing twins. The heat treated component microstructures and mechanical properties were compared with the as-built components in both the build direction (vertical) and perpendicular (horizontal) to the build direction. Vickers microindentation hardness (HV) values for the vertical and horizontal geometries averaged 227 and 220 for the as-built 50 and 100 micron layer components, and 185 and 282 for the corresponding heat treated components. The yield stress values were 387 MPa and 365 MPa for the as-built layer horizontal and vertical 50 micron layer geometries, and 330 MPa and 340 MPa for the as-built 100 micron layer components. For the heat treated 50 micron components, the yield stress values were 340 and 321 MPa for the horizontal and vertical geometries, and 581 and 489 MPa for the 100 micron layer components, respectively. The elongation for the 100 micron layer as-built horizontal components was 28% in contrast to 65% for the corresponding 100 micron heat treated layer components, an increase of 132% for the duplex grain structure. However, the coarse grains containing annealing twins and the equiaxed small grain islands in the duplex structure for the heat treated components contained continuous carbides in the grain boundaries, and this may indicate sensitization and a reduction in corrosion resistance. These findings point to the potential mechanical property advantage for heat treatment of Inconel 625 alloy 100 micron layer thickness components fabricated by EBPBF.

In this study, the friction factor of turbulent pipe flow for dried rice malt extract solutions is reduced experimentally to that of a Newtonian fluid. The friction factor is measured for four types of solutions at different culture times and concentrations. The results indicate that the experimental data points of the test solutions diverge from the maximum drag reduction asymptote at and above Re√f ≅ 200 and align parallel to those of Newtonian fluids. This drag reduction phenomenon differs from that of artificial high molecular polymer solutions. It is classified as a Type B drag reduction phenomenon of biopolymer solutions and fine solid particle suspensions. The order of drag reduction corresponds approximately to that of 5–50 ppm xanthan-gum solutions reported previously. Furthermore, the velocity profile in a turbulent pipe flow was predicted using a semi-theoretical equation, in which the friction factors were determined using the difference between the experimental results of the tested solutions and Newtonian fluids. The results indicate a more considerable thickening of the viscous sublayer in the turbulent pipe flow of the test solutions than that of Newtonian fluids.

The Kanchenjunga Conservation Area (KCA) is a high mountain protected area in eastern Nepal undergoing socio-economic and environmental changes that are unprecedented in the region’s history. In the following paper, we discuss recent changes involving new road construction, climate change, adventure tourism, and the wildlife/forest cover/medicinal plant sectors. Our assessments are based on the collective results of past and recent field research, remote sensing analysis, oral histories, and literature reviews. While similar changes are occurring in mountain protected areas (MPA) throughout Nepal, it is suggested that the KCA differs from other regions in that it still retains the option of conducting detailed feasibility, environmental, and impact assessments prior to the implementation of major change-associated projects, particularly the construction of roads. In turn, the KCA might avoid many of the environmental, social, and economic problems experienced elsewhere in Nepal, while enhancing its status, income-generating capacities, and sustainability as a global destination for adventure, nature, and cultural tourism.

This paper discusses the tectonics of the St. Peter and St. Paul Archipelago (SPSPA) in the Equato-rial Atlantic Ocean, based on the joint-system geometry which show a North-South shorten-ing/transpressional uplift tectonism, is active leading to exhumation of the sub-oceanic mantle. These islets are the summits of a sigmoidal submarine ridge formed by mantle ultramafic rocks. The ridge is crossed by the principal transform deformation zone of the northern transform fault of the St. Paul Multifault System. The South flank ridge exposes serpentinized mantle perido-tites, while the North flank exposes strongly deformed/fractured ultramylonites, recording duc-tile and brittle deformation at lithospheric conditions. The SPSPA show multiple joint systems cutting mylonitic foliation of the exposed rocks, forming three main families: high-angle paral-lel joints of tectonic origin, serpentinization-related joints with random direction and load-release low-angle parallel joints. The tectonic joints show an average direction of N31°E and N28°W, forming a conjugate system with a N1ºW compression axes, coherent with a trans-pressive stress field. Accordingly, the earthquakes focal mechanism close to the islets also shows N-S compression. The previously reported active uplift with an average rate of 1.5 mm/year and the directions of the joint system here reported agreeing with a present-day active N-S compres-sive field at a high angle with the direction of the transform fault.

Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (D_EP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, D_EP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by D_EP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by D_EP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated D_EP) at 20 V with 5 min intervals showed similar luciferase expression level to single D_EP application with 100 V. Histological observations showed the skin became thicker after a single D_EP at 100 V, whereas no apparent thickness changes was confirmed after repeated D_EP at 20 V with 5 min intervals. This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective in DNA vaccine delivery into skin tissue.

We have recently shown that 6-sulfo sialyl N-acetyllactosamine (LacNAc) in O-linked glycan recognized by the CL40 antibody is abundant in the pleural mesothelium under physiological conditions, and that these glycans are complementary synthesized by GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5) in mice. GlcNAc6ST3 is essential for the synthesis of R-10G-positive keratan sulfate (KS) in the brain. The predicted minimum epitope of the R-10G antibody is a dimeric asialo 6-sulfo LacNAc. Whether the R-10G-reactive KS/sulfated LacNAc oligosaccharides are also present in the pleural mesothelium was unknown. If any, the question of which GlcNAc6ST is the responsible enzyme was another issue to be examined as well. Here, we showed that R-10G-reactive glycans are as abundant in the pulmonary pleura as are CL40-reactive glycans, and that GlcNAc6ST3 is only partially involved in the synthesis of these pleural R-10G glycans, unlike in the adult brain. Unexpectedly, GlcNAc6ST2 is essential for the synthesis of R-10G-positive KS/sulfated LacNAc oligosaccharides in the lung pleura. The type of GlcNAc6ST involved in KS glycan biosynthesis and the magnitude of its contribution to the KS synthesis were found to differ among tissues in vivo. We show that GlcNAc6ST2 is required and sufficient for R-10G-reactive KS synthesis in the lung pleura. Interestingly, R-10G immunoreactivity in KSGal6ST (encoded by Chst1) and C6st1 (encoded by Chst3) double-deficient mouse lungs was markedly increased. Muc16, a mucin molecule, was shown to be a candidate carrier protein for the pleural R-10G-reactive glycans. These results suggested that R-10G-positive KS/sulfated LacNAc oligosaccharides may play a role in mesothelial cell proliferation and differentiation. Further elucidation of the functions of sulfated glycans synthesized by GlcNAc6ST2 and GlcNAc6ST3, such as R-10G and CL40 glycans, in pathological conditions may lead to a better understanding of the underlying mechanisms of the physiopathology of lung mesothelium.

Chemotherapy for lung cancer has made remarkable progress, and its selection has been subdivided by genetic analysis. Although response evaluation criteria in solid tumors (RECIST) is a simple and highly objective evaluation method, it has been pointed out that it has the disadvantage of not being able to accurately evaluate the therapeutic effect of molecularly targeted drugs and immune checkpoint inhibitors. The purpose of this study is to determine whether quantitative evaluation of DWIBS is useful in determining the effectiveness of treatment for lung cancer. There were 31 patients with lung cancer and 56 patterns were obtained. First, the determination of treatment effect (PD, SD, PR) based on RECIST was performed on CT. Second, tDV and ADC (median) were measured using BD score from DWI images taken at the same time, and the rate of change was calculated. Then, we compared and examined the correlation between RECIST and the rate of change in tDV. There were correlations between RECIST and the rate of change in tDV in PD and PR cases respectively. Compared RECIST on CT, DWIBS using BD score would be more accurate for response evaluation of treatment. There was a tendency that tDV decreased with increasing ADC values, but some of the cases had a dissociated response with increasing ADC values and increasing tDV. Thus, since the color display of ADC values allows us to infer their contents, it would be useful for the evaluation of cases such as dissociated response and pseudoprogression, which are suspected to be atypical responses that are difficult to evaluate with RECIST and other methods.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n=207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis” Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.